obese mice

Summary

Summary: Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.

Top Publications

  1. pmc Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
    P D Cani
    Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Louvain Drug Research Institute, Universite Catholique de Louvain, Brussels, Belgium
    Gut 58:1091-103. 2009
  2. ncbi Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans
    Saverio Cinti
    Institute of Normal Human Morphology, University of Ancona, Ancona, Italy
    J Lipid Res 46:2347-55. 2005
  3. pmc Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice
    Shiho Fujisaka
    First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, Tokyo, Japan
    Diabetes 58:2574-82. 2009
  4. ncbi Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice
    Jianping Ye
    Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA
    Am J Physiol Endocrinol Metab 293:E1118-28. 2007
  5. pmc MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity
    Hajime Kanda
    Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    J Clin Invest 116:1494-505. 2006
  6. pmc Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance
    Haiyan Xu
    Millennium Pharmaceuticals, Cambridge, Massachusetts, USA
    J Clin Invest 112:1821-30. 2003
  7. ncbi Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice
    H Chen
    Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02139, USA
    Cell 84:491-5. 1996
  8. ncbi Effects of the obese gene product on body weight regulation in ob/ob mice
    M A Pelleymounter
    Department of Neurobiology, Amgen, Inc, Thousand Oaks, CA 91320, USA
    Science 269:540-3. 1995
  9. ncbi Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis
    Paola Brun
    Department of Histology, Univ of Padua, Via Gabelli 63, Padova, Italy
    Am J Physiol Gastrointest Liver Physiol 292:G518-25. 2007
  10. ncbi Targeted disruption of the melanocortin-4 receptor results in obesity in mice
    D Huszar
    Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    Cell 88:131-41. 1997

Detail Information

Publications321 found, 100 shown here

  1. pmc Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
    P D Cani
    Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Louvain Drug Research Institute, Universite Catholique de Louvain, Brussels, Belgium
    Gut 58:1091-103. 2009
    ....
  2. ncbi Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans
    Saverio Cinti
    Institute of Normal Human Morphology, University of Ancona, Ancona, Italy
    J Lipid Res 46:2347-55. 2005
    ..We demonstrate that >90% of all macrophages in WAT of obese mice and humans are localized to dead adipocytes, where they fuse to form syncytia that sequester and scavenge the ..
  3. pmc Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice
    Shiho Fujisaka
    First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, Tokyo, Japan
    Diabetes 58:2574-82. 2009
    ..To characterize the phenotypic changes of adipose tissue macrophages (ATMs) under different conditions of insulin sensitivity...
  4. ncbi Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice
    Jianping Ye
    Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA
    Am J Physiol Endocrinol Metab 293:E1118-28. 2007
    ..In this study, we provide experimental evidence that hypoxia occurs in adipose tissue in obese mice and that adipose hypoxia may contribute to the endocrine alterations...
  5. pmc MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity
    Hajime Kanda
    Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    J Clin Invest 116:1494-505. 2006
    ..These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice...
  6. pmc Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance
    Haiyan Xu
    Millennium Pharmaceuticals, Cambridge, Massachusetts, USA
    J Clin Invest 112:1821-30. 2003
    ..there is evidence of significant infiltration of macrophages, but not neutrophils and lymphocytes, into WAT of obese mice, with signs of adipocyte lipolysis and formation of multinucleate giant cells...
  7. ncbi Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice
    H Chen
    Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02139, USA
    Cell 84:491-5. 1996
    ....
  8. ncbi Effects of the obese gene product on body weight regulation in ob/ob mice
    M A Pelleymounter
    Department of Neurobiology, Amgen, Inc, Thousand Oaks, CA 91320, USA
    Science 269:540-3. 1995
    ..These data suggest that the OB protein regulates body weight and fat deposition through effects on metabolism and appetite...
  9. ncbi Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis
    Paola Brun
    Department of Histology, Univ of Padua, Via Gabelli 63, Padova, Italy
    Am J Physiol Gastrointest Liver Physiol 292:G518-25. 2007
    ..determine the effect of obesity on intestinal mucosal integrity and portal blood endotoxemia in two strains of obese mice: leptin-deficient (ob/ob) and hyperleptinemic (db/db) mice...
  10. ncbi Targeted disruption of the melanocortin-4 receptor results in obesity in mice
    D Huszar
    Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    Cell 88:131-41. 1997
    ..Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R...
  11. ncbi Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression
    Motohiro Sekiya
    Department of Internal Medicine, Tokyo University Graduate School of Medicine, Tokyo, Japan
    Hepatology 38:1529-39. 2003
    ..In conclusion, PUFAs ameliorate obesity-associated symptoms, such as hepatic steatosis and insulin resistance, presumably through both down-regulation of SREBP-1 and activation of PPARalpha...
  12. pmc Increased oxidative stress in obesity and its impact on metabolic syndrome
    Shigetada Furukawa
    Department of Medicine and Pathophysiology, Graduate School of Medicine, Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    J Clin Invest 114:1752-61. 2004
    ..Production of ROS increased selectively in adipose tissue of obese mice, accompanied by augmented expression of NADPH oxidase and decreased expression of antioxidative enzymes...
  13. ncbi Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance
    Nozomu Kamei
    Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113 8655, Japan
    J Biol Chem 281:26602-14. 2006
    ..We concluded that both paracrine and endocrine effects of MCP-1 may contribute to the development of insulin resistance in aP2-MCP-1 mice...
  14. ncbi Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression
    G M Lord
    Imperial College School of Medicine, Department of Immunology, The Hammersmith Hospital, London, UK
    Nature 394:897-901. 1998
    ..Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation...
  15. ncbi Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta
    M Yuan
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Science 293:1673-7. 2001
    ..These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization...
  16. pmc The L-4F mimetic peptide prevents insulin resistance through increased levels of HO-1, pAMPK, and pAKT in obese mice
    Stephen J Peterson
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    J Lipid Res 50:1293-304. 2009
    ..The anti-obesity effects of L-4F are manifested by a decrease in visceral fat content with reciprocal increases in adiponectin, pAMPK, pAKT, and phosphorylation of insulin receptors with improved insulin sensitivity...
  17. ncbi Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet
    Ji Hye Kang
    Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea
    Obesity (Silver Spring) 18:780-7. 2010
    ..Male C57BL/6 obese mice fed a high-fat diet for 10 weeks received a supplement of 0...
  18. ncbi Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice
    Xing Xian Yu
    Department of Antisense Drug Discovery, Isis Pharmaceuticals, Inc, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
    Hepatology 42:362-71. 2005
    ..the role of acyl-coenzyme A:diacylglycerol acyltransferase 2 (DGAT2) in glucose and lipid metabolism in obese mice by reducing its expression in liver and fat with an optimized antisense oligonucleotide (ASO)...
  19. ncbi p53 Activation in adipocytes of obese mice
    Naoya Yahagi
    Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113 8655, Japan
    J Biol Chem 278:25395-400. 2003
    ..Thus, the activation of p53 might constitute a negative feedback loop against excess fat accumulation in adipocytes. In conclusion, we discovered a novel role of p53 in the pathophysiology of obesity...
  20. ncbi Reduced content and preserved translocation of glucose transporter (GLUT 4) in white adipose tissue of obese mice
    U F Machado
    Department of Physiology and Biophysics, University of Sao Paulo, Brazil
    Physiol Behav 55:621-5. 1994
    ..75 U/kg, EV) promoted, 10 min later, no significant change on glycemia of both AuTG and MSG obese mice, but control mice showed a decrease of 30% (p < 0.001)...
  21. pmc Obesity induces a phenotypic switch in adipose tissue macrophage polarization
    Carey N Lumeng
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Clin Invest 117:175-84. 2007
    ..To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice...
  22. ncbi Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice
    Hui Young Lee
    Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 151 742, Korea
    Biochim Biophys Acta 1761:736-44. 2006
    ..rhamnosus PL60, a human originated bacterium that produces t10, c12-conjugated linoleic acid, on diet-induced obese mice. After 8 weeks of feeding, L...
  23. pmc Insulin-stimulated cardiac glucose oxidation is increased in high-fat diet-induced obese mice lacking malonyl CoA decarboxylase
    John R Ussher
    Cardiovascular Research Group, University of Alberta, Edmonton, Canada
    Diabetes 58:1766-75. 2009
    ....
  24. ncbi Sepsis-induced intestinal microvascular and inflammatory responses in obese mice
    Georg Singer
    Department of Pediatric Surgery, Medical University of Graz, Graz, Austria
    Shock 31:275-9. 2009
    ..Sepsis promotes more intense inflammatory and thrombogenic responses in the gut microcirculation of obese mice than in their lean counterparts...
  25. pmc A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition
    Jiyoung Lee
    Department of Molecular and Integrative Physiology, University of Illinois, Urbana Champaign, Illinois 61801, USA
    J Biol Chem 285:12604-11. 2010
    ..Remarkably, miR-34a levels were elevated, and SIRT1 protein levels were reduced in diet-induced obese mice, and FXR activation in these mice reversed the miR-34a and SIRT1 levels, indicating an intriguing link among FXR ..
  26. ncbi Laboratory animals exhibiting obesity and diabetes syndromes
    L Herberg
    Metabolism 26:59-99. 1977
    ..Although the primary causes of the syndrome remain unclear in some strains, an involvement of hypothalamic feeding centers has been implicated...
  27. ncbi Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice
    Makoto Tomaru
    Gerodontology, Department of Gerodontology, Division of Gerontology and Gerodontology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan Environmental Health Sciences Division, National Institute for Environmental Studies, Ibaraki, Japan
    Nutrition 23:351-5. 2007
    ..The present study examined whether dietary supplementation with cacao liquor proanthocyanidins (CLPr) could prevent elevation of blood glucose levels in mice with diabetes mellitus and obesity...
  28. ncbi Cardiac lipid accumulation associated with diastolic dysfunction in obese mice
    Christina Christoffersen
    Departments of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2100
    Endocrinology 144:3483-90. 2003
    ..The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice...
  29. pmc L-4F treatment reduces adiposity, increases adiponectin levels, and improves insulin sensitivity in obese mice
    Stephen J Peterson
    Department of Medicine, New York Medical College, Valhalla, NY 10595, USA
    J Lipid Res 49:1658-69. 2008
    ..enzymes and is vasoprotective in a rat model of diabetes, would ameliorate insulin resistance and diabetes in obese mice. L-4F (2 mg/kg/d) administered to ob/ob mice for 6 weeks limited weight gain without altering food intake, ..
  30. ncbi Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP
    L J Slieker
    Endocrine Research and Technology Core Divisions, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    J Biol Chem 271:5301-4. 1996
    ..Furthermore, leptin might regulate its own expression through a feedback mechanism involving the hypothalamic pituitary axis...
  31. ncbi Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions
    Toshimasa Yamauchi
    Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113 8655, Japan
    Nat Med 13:332-9. 2007
    ..Therefore, AdipoR1 and R2 serve as the predominant receptors for adiponectin in vivo and play important roles in the regulation of glucose and lipid metabolism, inflammation and oxidative stress in vivo...
  32. pmc miR-375 maintains normal pancreatic alpha- and beta-cell mass
    Matthew N Poy
    Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, ETH Zurich, CH 8093 Zurich, Switzerland
    Proc Natl Acad Sci U S A 106:5813-8. 2009
    ..In contrast, pancreatic islets of obese mice (ob/ob), a model of increased beta-cell mass, exhibit increased expression of miR-375...
  33. ncbi Improved glucose and lipid metabolism in genetically obese mice lacking aP2
    K T Uysal
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Endocrinology 141:3388-96. 2000
    ..Taken together, the data indicate that in obesity, aP2-deficiency not only improves peripheral insulin resistance but also preserves pancreatic beta cell function and has beneficial effects on lipid metabolism...
  34. ncbi Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function
    K T Uysal
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Nature 389:610-4. 1997
    ..To investigate the role of TNF-alpha in obesity and insulin resistance, we have generated obese mice with a targeted null mutation in the gene encoding TNF-alpha and those encoding the two receptors for TNF-alpha...
  35. pmc Increased brain microvascular MMP-9 and incidence of haemorrhagic transformation in obese mice after experimental stroke
    Barry W McColl
    Faculty of Life Sciences, University of Manchester, Manchester, UK
    J Cereb Blood Flow Metab 30:267-72. 2010
    ..incidence of haemorrhagic transformation and the volume of ischaemic brain damage were significantly greater in obese mice. Blood-brain barrier permeability and brain microvascular MMP-9 expression were also markedly increased in obese ..
  36. ncbi Low-carbohydrate diet versus caloric restriction: effects on weight loss, hormones, and colon tumor growth in obese mice
    Karrie E Wheatley
    Department of Human Ecology, Division of Nutritional Sciences, The University of Texas at Austin, TX 78712, USA
    Nutr Cancer 60:61-8. 2008
    ..IGF-I levels were lower in the LC group (320.0 +/- 39.9 ng/ml) than the HF group, but tumor growth did not differ. These data suggest LC diets do not slow colon tumor growth in obese mice.
  37. pmc Proteasomal degradation of retinoid X receptor alpha reprograms transcriptional activity of PPARgamma in obese mice and humans
    Bruno Lefebvre
    Univ Lille Nord de France, Lille, France
    J Clin Invest 120:1454-68. 2010
    ..Here we report that the PPARgamma signaling pathway operates differently in the visceral WAT of lean and obese mice. PPARgamma in visceral, but not subcutaneous, WAT from obese mice displayed increased sensitivity to activation ..
  38. pmc Leptin inhibits insulin gene transcription and reverses hyperinsulinemia in leptin-deficient ob/ob mice
    J Seufert
    The Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 96:674-9. 1999
    ..Thus leptin exerts inhibitory effects on both insulin secretion and insulin gene expression in pancreatic beta-cells, but by different cellular mechanisms...
  39. ncbi Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts
    Pradip K Mazumder
    Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, University of Utah, 15 North 2030 East, Building 533, Room 3410B, Salt Lake City, UT 84112, USA
    Diabetes 53:2366-74. 2004
    ....
  40. ncbi Intestinal, adipose, and liver inflammation in diet-induced obese mice
    Hong Li
    Department of Integrative Pharmacology, AstraZeneca R and D Molndal, S 431 83 Molndal, Sweden
    Metabolism 57:1704-10. 2008
    ..Body weight of diet-induced obese mice was greatly increased, with evidence of systemic inflammation, insulin resistance, and liver steatosis...
  41. ncbi Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y
    J C Erickson
    Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Box 357370, Seattle, WA 98195 7370, USA
    Science 274:1704-7. 1996
    ..These results suggest that NPY is a central effector of leptin deficiency...
  42. ncbi Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance
    Mitsuhisa Tabata
    Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1 1 1 Honjo, Kumamoto 860 8556, Japan
    Cell Metab 10:178-88. 2009
    ..Angptl2 deletion ameliorated adipose tissue inflammation and systemic insulin resistance in diet-induced obese mice. Conversely, Angptl2 overexpression in adipose tissue caused local inflammation and systemic insulin resistance ..
  43. pmc Monocyte chemoattractant protein 1 in obesity and insulin resistance
    Peter Sartipy
    Department of Cell Biology, Division of Vascular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, VB 3, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 100:7265-70. 2003
    ..expression and secretion of MCP-1 both in vitro in insulin-resistant (IR) 3T3-L1 adipocytes and in vivo in IR obese mice (ob/ob). Thus, MCP-1 resembles other previously described genes (e.g...
  44. pmc Reducing glycosphingolipid content in adipose tissue of obese mice restores insulin sensitivity, adipogenesis and reduces inflammation
    Marco van Eijk
    Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    PLoS ONE 4:e4723. 2009
    ..In conclusion, pharmacological lowering of glycosphingolipids by inhibition of glucosylceramide biosynthesis improves adipocyte function and as a consequence reduces inflammation in adipose tissue of obese animals...
  45. ncbi The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-alpha in 3T3-L1 adipocytes and is a target for transactivation by PPARgamma
    Ji Young Kim
    Dept of Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, OH 43614, USA
    Am J Physiol Endocrinol Metab 291:E115-27. 2006
    ..Our findings identify the novel lipase ATGL to be a target gene for TNF-alpha and insulin action in adipocytes and reveal that it is subject to transcriptional control by PPARgamma-mediated signals...
  46. ncbi Endoplasmic reticulum stress plays a central role in development of leptin resistance
    Lale Ozcan
    Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Cell Metab 9:35-51. 2009
    ..endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in the hypothalamus of obese mice inhibits leptin receptor signaling...
  47. ncbi Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice
    Ayumu Hirata
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2 2 B5 Yamada oka, Suita, Osaka 565 0871, Japan
    Cardiovasc Res 84:164-72. 2009
    ..However, the significance of MR in fat remains elusive. Here we investigated whether MR blockade attenuates obesity-related insulin resistance and improves adipocyte dysfunction...
  48. ncbi Zinc-alpha2-glycoprotein is involved in regulation of body weight through inhibition of lipogenic enzymes in adipose tissue
    F Y Gong
    Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Int J Obes (Lond) 33:1023-30. 2009
    ..Zinc-alpha2-glycoprotein (ZAG) was found to influence lipolysis in adipose tissue and has recently been proposed as a candidate factor in the regulation of body weight...
  49. ncbi Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin
    Miguel Lopez
    Department of Physiology, School of Medicine, University of Santiago de Compostela, S Francisco s n, 15782 Santiago de Compostela A Coruña, Spain
    Cell Metab 7:389-99. 2008
    ..Overall, our results indicate that modulation of hypothalamic fatty acid metabolism specifically in the VMH in response to ghrelin is a physiological mechanism that controls feeding...
  50. ncbi Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting and [corrected] in ob/ob and db/db mice, but is stimulated by leptin
    T M Mizuno
    Fishberg Center for Neurobiology, Department of Geriatrics, Mount Sinai School of Medicine, New York, New York 10029 6574, USA
    Diabetes 47:294-7. 1998
    ....
  51. ncbi Leptin and the immune system: how nutritional status influences the immune response
    G Matarese
    Laboratorio di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di Napoli Federico II, Via S Pansini, 5 80131 Napoli, Italy
    Eur Cytokine Netw 11:7-14. 2000
    ..According to this view, leptin might represent an important target for immune intervention in a variety of pathophysiological conditions...
  52. ncbi Deconstructing and reconstructing obesity-induced diabetes (diabesity) in mice
    Peter C Reifsnyder
    Jackson Laboratory, Bar Harbor, Maine 04609 1500, USA
    Diabetes 51:825-32. 2002
    ....
  53. pmc Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice
    Angela Burgess
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA
    Hypertension 56:1124-30. 2010
    ..inducer, cobalt protoporphyrin (CoPP), on regulation of adiposity and glucose levels in both female and male obese mice. Both lean and obese mice were administered CoPP intraperitoneally (3 mg/kg once per week) for 6 weeks...
  54. ncbi Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice
    I Murano
    Institute of Normal Human Morphology, University of Ancona Politecnica delle Marche, Ancona, Italy
    J Lipid Res 49:1562-8. 2008
    ..In this study we quantified CLS in visceral and subcutaneous depots from two strains of genetically obese mice, db/db and ob/ob. In both strains, CLS were prevalent in visceral compared with subcutaneous fat...
  55. pmc IKKbeta suppression of TSC1 function links the mTOR pathway with insulin resistance
    Dung Fang Lee
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Int J Mol Med 22:633-8. 2008
    ..V-Lepob/J mice. Collectively, dysregulation of the TSC1/ TSC2/mTOR signaling pathway by IKKbeta is a common molecular switch for both cancer pathogenesis and diet- and obesity-induced insulin resistance...
  56. pmc Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters
    Markus Feuerer
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts, USA
    Nat Med 15:930-9. 2009
    ..These observations suggest that harnessing the anti-inflammatory properties of T(reg) cells to inhibit elements of the metabolic syndrome may have therapeutic potential...
  57. pmc FGF-21 as a novel metabolic regulator
    Alexei Kharitonenkov
    Lilly Research Laboratories, Division of Eli Lilly and Co, Indianapolis, Indiana 46285, USA
    J Clin Invest 115:1627-35. 2005
    ..Thus, we conclude that FGF-21, which we have identified as a novel metabolic factor, exhibits the therapeutic characteristics necessary for an effective treatment of diabetes...
  58. ncbi The physiology of obese-hyperglycemic mice [ob/ob mice]
    Per Lindstrom
    Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umea University, Umea, Sweden
    ScientificWorldJournal 7:666-85. 2007
    ..ob/ob Mice are well suited for studies on the interaction between leptin and insulin, and for studies on initial aspects of metabolic disturbances leading to type-2 diabetes...
  59. ncbi Increased low-density lipoprotein oxidation and impaired high-density lipoprotein antioxidant defense are associated with increased macrophage homing and atherosclerosis in dyslipidemic obese mice: LCAT gene transfer decreases atherosclerosis
    Ann Mertens
    Cardiovascular Research Unit at the Center for Experimental Surgery and Anesthesiology, Katholieke Universiteit Leuven, Campus Gasthuisberg, O and N, Herestraat 49, B 3000 Leuven, Belgium
    Circulation 107:1640-6. 2003
    ..We investigated the association between oxidation of apolipoprotein B-containing lipoproteins, high-density lipoprotein (HDL) antioxidant defense, and atherosclerosis in these mice...
  60. pmc Selective impairment in dendritic cell function and altered antigen-specific CD8+ T-cell responses in diet-induced obese mice infected with influenza virus
    Alexia G Smith
    Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599 7461, USA
    Immunology 126:268-79. 2009
    ..We have previously reported that diet-induced obese mice are more susceptible to morbidity and mortality during influenza infection than lean mice...
  61. ncbi Leptin-regulated endocannabinoids are involved in maintaining food intake
    V Di Marzo
    Endocannabinoid Research Group, Istituto per la Chimica di Molecole di Interesse Biologico, CNR, 80072, Arco Felice, Naples, Italy
    Nature 410:822-5. 2001
    ..These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin...
  62. ncbi Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass
    P Ducy
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 100:197-207. 2000
    ..This study identifies leptin as a potent inhibitor of bone formation acting through the central nervous system and therefore describes the central nature of bone mass control and its disorders...
  63. ncbi Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice
    M W Schwartz
    Department of Medicine, University of Washington, Seattle, USA
    Diabetes 45:531-5. 1996
    ....
  64. ncbi Angiogenesis inhibitor, TNP-470, prevents diet-induced and genetic obesity in mice
    Ebba Brakenhielm
    Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
    Circ Res 94:1579-88. 2004
    ..Our findings suggest that similarly to growth and organogenesis in other tissues, adipose tissue growth is dependent on angiogenesis. Our observations may have conceptual implications for the prevention of obesity and related disorders...
  65. pmc Regulation of PPAR gamma gene expression by nutrition and obesity in rodents
    A Vidal-Puig
    Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215, USA
    J Clin Invest 97:2553-61. 1996
    ..adipose tissue expression of PPAR gamma (in normal mice) and induces PPAR gamma 2 mRNA expression in liver (in obese mice)...
  66. ncbi Pitavastatin inhibits azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice
    Yoichi Yasuda
    Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
    Cancer Sci 101:1701-7. 2010
    ..on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were administrated weekly subcutaneous injections of AOM (15 mg/kg body weight) for 4 weeks and ..
  67. ncbi Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin
    F F Chehab
    Department of Laboratory Medicine, University of California, San Francisco, 94143 0134, USA
    Nat Genet 12:318-20. 1996
    ..We show here that repeated administration of only the recombinant human ob protein, leptin, into homozygous female ob/ob mice can correct their sterility, thus resulting in ovulation, pregnancy and parturition...
  68. ncbi Selective lack of the C16:0 fatty acid isoform of sulfatide in pancreas of type II diabetic animal models
    Maria Blomqvist
    Institute of Clinical Neuroscience, Experimental Neuroscience Section, The Sahlgrenska Academy at Goteborg University, Sahlgrenska University Hospital Molndal, Sweden
    APMIS 111:867-77. 2003
    ..Thus, it is hypothesized that the selection of sulfatide isomers in pancreas might be a genetic factor contributing to disease development in type II diabetic animal models...
  69. pmc Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
    Mitsuhiro Watanabe
    Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS INSERM ULP, Illkirch, France
    J Clin Invest 113:1408-18. 2004
    ..These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia...
  70. pmc Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice
    J K Howard
    Endocrine Unit and Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom
    J Clin Invest 104:1051-9. 1999
    ..In vitro, leptin protected thymocytes from dexamethasone-induced apoptosis. These data indicate that reduced circulating leptin concentrations are pivotal in the pathogenesis of starvation-induced lymphoid atrophy...
  71. pmc Astrocyte leptin receptor (ObR) and leptin transport in adult-onset obese mice
    Weihong Pan
    Blood Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA
    Endocrinology 149:2798-806. 2008
    ....
  72. pmc A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice
    K L Grove
    Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA
    Int J Obes (Lond) 34:989-1000. 2010
    ..was to systematically document depot- and sex-related differences in the accumulation of adipose tissue and gene expression, comparing differentially expressed genes in diet-induced obese mice with mice maintained on a chow diet.
  73. ncbi Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets
    V A Gault
    School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine, Northern Ireland, UK
    Diabetologia 50:1752-62. 2007
    ..This study examined the ability of (Pro(3))GIP to counter the development of obesity, insulin resistance and diabetes in mice fed high-fat and cafeteria diets...
  74. ncbi Inflammatory and injury responses to ischemic stroke in obese mice
    Satoshi Terao
    Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA
    Stroke 39:943-50. 2008
    ..This study tested the hypothesis that obesity exacerbates the cerebrovascular dysfunction and tissue injury induced by brain ischemia and reperfusion...
  75. ncbi Antiobesity effects of yerba maté extract (Ilex paraguariensis) in high-fat diet-induced obese mice
    Demétrius P Arçari
    Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Braganca Paulista, Brazil
    Obesity (Silver Spring) 17:2127-33. 2009
    ..The F4/80 levels were determined by immunoblotting. We found that obese mice treated with yerba maté exhibited marked attenuation of weight gain, adiposity, a decrease in epididymal fat-..
  76. ncbi Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice
    Renaud Dentin
    Departement d Endocrinologie, Institut Cochin, Métabolisme et Cancer, 24 rue du Faubourg St Jacques, Paris 75014, France
    Diabetes 55:2159-70. 2006
    ..Taken together, our results demonstrate that ChREBP is central for the regulation of lipogenesis in vivo and plays a determinant role in the development of the hepatic steatosis and of insulin resistance in ob/ob mice...
  77. ncbi Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice
    Yoshiyuki Sasaki
    Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, and Department of Hospital Pharmacy, School of Medicine, Kanazawa University, 13 1 Takara machi, Kanazawa 920 8641, Japan
    Life Sci 85:490-8. 2009
    ..In this study, we investigated the effects of varying the dose of MSG on the resulting obesity and diabetes mellitus...
  78. ncbi Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice
    F Dong
    Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, 82071, USA
    J Endocrinol 188:25-36. 2006
    ..Ca(2+) transients were evaluated in ventricular myocytes from lean control and leptin-deficient ob/ob obese mice at 12 weeks of age. Cardiac ultrastructure was evaluated using transmission electron microscopy...
  79. ncbi Disrupted signaling and inhibited regeneration in obese mice with fatty livers: implications for nonalcoholic fatty liver disease pathophysiology
    S Q Yang
    Department of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
    Hepatology 34:694-706. 2001
    ..This contributes to NAFLD pathophysiology by inhibiting proliferation, increasing injury, and limiting function in fatty livers...
  80. ncbi Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice
    Mathieu Membrez
    Nestle Research Center, P O Box 44, CH 1000 Lausanne, Switzerland
    FASEB J 22:2416-26. 2008
    ....
  81. ncbi Quantitative trait loci for obesity and insulin resistance (Nob1, Nob2) and their interaction with the leptin receptor allele (LeprA720T/T1044I) in New Zealand obese mice
    R Kluge
    Institute of Animal Research, Medical Faculty of the Technical University, Aachen, Germany
    Diabetologia 43:1565-72. 2000
    ..To locate genes responsible for obesity and insulin resistance, a backcross model of New Zealand obese (NZO) mice with the lean Swiss/Jackson Laboratory (SJL) strain was stablished...
  82. pmc Allergic airway responses in obese mice
    Richard A Johnston
    Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
    Am J Respir Crit Care Med 176:650-8. 2007
    ..Epidemiologic data indicate an increased incidence of asthma in the obese...
  83. ncbi Downregulation of adiponectin/AdipoR2 is associated with steatohepatitis in obese mice
    Yanhua Peng
    Department of Surgery, University of South Florida, Tampa, FL, USA
    J Gastrointest Surg 13:2043-9. 2009
    ..Adiponectin regulates fat storage, energy expenditure, and inflammation. We propose that high fat diet induces steatohepatitis, reduces serum adiponectin, and liver adiponectin receptors...
  84. ncbi Genetic and genomic studies of the BTBR ob/ob mouse model of type 2 diabetes
    Susanne M Clee
    Department of Biochemistry, University of Wisconsin Madison, Madison, WI 53706, USA
    Am J Ther 12:491-8. 2005
    ..Conversely, hepatic lipogenic gene expression increases in obese mice, but to a much greater extent in the diabetes-resistant C57BL/6 strain...
  85. ncbi On raising energy expenditure in ob/ob mice
    J Himms-Hagen
    Science 276:1132-3. 1997
  86. ncbi Increased high density lipoprotein (HDL), defective hepatic catabolism of ApoA-I and ApoA-II, and decreased ApoA-I mRNA in ob/ob mice. Possible role of leptin in stimulation of HDL turnover
    D L Silver
    Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 274:4140-6. 1999
    ..The studies reveal a specific HDL particle catabolic pathway that is down-regulated in ob/ob mice and suggest that HDL apolipoprotein turnover may be regulated by obesity and/or leptin signaling...
  87. ncbi Impairment of dendritic cell functionality and steady-state number in obese mice
    Laurence Macia
    Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8527, Institut de Biologie de Lille Institut Pasteur de Lille, 1 Rue Albert Calmette, 59019 Lille Cedex, France
    J Immunol 177:5997-6006. 2006
    ..In this report, we show that dendritic cells (DCs), major APCs involved in T lymphocyte priming, are affected in obese mice. Both their function and their steady-state number are disturbed...
  88. ncbi Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice
    Jianguo Li
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
    J Appl Physiol (1985) 99:1643-8. 2005
    ..In conclusion, we have shown that CIH may exacerbate preexisting fatty liver of obesity via upregulation of the pathways of lipid biosynthesis in the liver...
  89. ncbi Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans
    Yu Wang
    Genome Research Center and Department of Biochemistry, University of Hong Kong, Hong Kong, China
    Clin Chem 53:34-41. 2007
    ..Because lipocalin-2 is abundantly expressed in adipose tissue and liver, we investigated its relevance to obesity-related pathologies...
  90. pmc Fenofibrate inhibits adipocyte hypertrophy and insulin resistance by activating adipose PPARalpha in high fat diet-induced obese mice
    Sunhyo Jeong
    Department of Life Sciences, Mokwon University, Daejeon 302 729, Korea
    Exp Mol Med 41:397-405. 2009
    ..Consistent with this hypothesis, fenofibrate decreased visceral fat mass and adipocyte size in high fat diet-fed obese mice, and concomitantly increased the expression of PPARalpha target genes involved in fatty acid beta-oxidation in ..
  91. ncbi Hyperphagia, lower body temperature, and reduced running wheel activity precede development of morbid obesity in New Zealand obese mice
    Hella S Jürgens
    Department of Pharmacology, German Institute of Human Nutrition Potsdam Rehbrucke, Nuthetal, Germany
    Physiol Genomics 25:234-41. 2006
    ..Because NZO mice differ strikingly from the ob/ob strain in their resistance to cold stress, we suggest that the molecular defects causing hyperphagia in NZO mice are located distal from leptin and its receptor...
  92. ncbi Leptin activation of corticosterone production in hepatocytes may contribute to the reversal of obesity and hyperglycemia in leptin-deficient ob/ob mice
    Yanjun Liu
    Division of Endocrinology, Charles R Drew University of Medicine and Sciences, UCLA School of Medicine, 1731 E 120th Street, Los Angeles, CA 90059, USA
    Diabetes 52:1409-16. 2003
    ..These findings suggest that the liver-specific interaction of leptin with 11beta-HSD1 is involved in the development of obesity and insulin resistance in ob/ob mice...
  93. ncbi Cell type-specific expression and coregulation of murine resistin and resistin-like molecule-alpha in adipose tissue
    Michael W Rajala
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Mol Endocrinol 16:1920-30. 2002
    ..Additionally, we show that resistin and RELMalpha levels are not subject to regulation by proinflammatory stimuli. Finally, acute hyperglycemia leads to up-regulation of resistin and RELMalpha transcription in various adipose depots...
  94. pmc Normalization of obesity-associated insulin resistance through immunotherapy
    Shawn Winer
    Department of Pediatrics and Immunology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Nat Med 15:921-9. 2009
    ..The eventual failure of this control, with expanding adiposity and pathogenic VAT T cells, can successfully be reversed by immunotherapy...
  95. pmc Enhanced production of IL-17A during zymosan-induced peritonitis in obese mice
    Maria Pini
    Department of Kinesiology, University of Illinois, Chicago, IL 60612, USA
    J Leukoc Biol 87:51-8. 2010
    ..Peritoneal cells and adipose tissue obtained from ZY-injected obese mice expressed significantly higher levels of IL-17A mRNA compared with lean mice...
  96. ncbi The leptin-deficient (ob/ob) mouse: a new animal model of peripheral neuropathy of type 2 diabetes and obesity
    Viktor R Drel
    Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd, Baton Rouge, LA 70808, USA
    Diabetes 55:3335-43. 2006
    ..The results support the role for increased aldose reductase activity in functional and structural changes of PDN in type 2 diabetes...
  97. ncbi Reduction of low molecular weight protein-tyrosine phosphatase expression improves hyperglycemia and insulin sensitivity in obese mice
    Sanjay K Pandey
    Metabolic Disease Program, Antisense Drug Discovery, Isis Pharmaceuticals, Carlsbad, CA 92008, USA
    J Biol Chem 282:14291-9. 2007
    ..These data demonstrate that LMW-PTP is a key negative regulator of insulin action and a potential novel target for the treatment of insulin resistance and type 2 diabetes...
  98. ncbi Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice
    Lauren P Shearman
    Department of Pharmacology, Merck Research Laboratories, P O Box 2000, RY80Y 150, Rahway, New Jersey 07065, USA
    Endocrinology 147:1517-26. 2006
    ..The decreased obesity observed in SPM-treated DIO mice provides validation for ghrelin neutralization as a potential antiobesity therapy...
  99. ncbi Identification of SOCS-3 as a potential mediator of central leptin resistance
    C Bjørbaek
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell 1:619-25. 1998
    ..In conclusion, SOCS-3 is a leptin-inducible inhibitor of leptin signaling, and a potential mediator of leptin resistance in obesity...
  100. ncbi Leptin regulates proinflammatory immune responses
    S Loffreda
    Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA
    FASEB J 12:57-65. 1998
    ..These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity...
  101. ncbi Antiobesity action of a daidzein derivative on male obese mice induced by a high-fat diet
    Yongqi Guo
    Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, PR China
    Nutr Res 29:656-63. 2009
    ..this study, we investigate the effects of Dzd on body weight, adipose tissue, blood, and liver lipid levels in obese mice fed a high-fat diet...

Research Grants66

  1. Iron, Metabolic Regulation and Type 2 Diabetes Risk
    Donald A McClain; Fiscal Year: 2013
    ..Initial exploration of mechanisms will include altered heme and NAD levels, the latter resulting in altered AMPK signaling. ..
  2. PUFA Synthesis and the Control of Hepatic Metabolism
    Donald B Jump; Fiscal Year: 2013
    ..gene identification-58 (CGI58, ATGL co-activator) and short &long chain acylcarnitines in livers of obese mice. This outcome suggests Elovl5 activity controls hepatic triglyceride (TAG) by regulating TAG hydrolysis and ..
  3. Thyroid Hormone Action
    THOMAS STERLING SCANLAN; Fiscal Year: 2013
    ..daily dosing of T1AM with doses approaching the 5g/kg range lead to significant weight loss in diet-induced obese mice. Results from pair-feeding studies unambiguously demonstrate that the observed chronically administered, low-..
  4. Monocyte activation and the role of CD11c in obesity-linked metabolic syndrome
    Huaizhu Wu; Fiscal Year: 2013
    ..endothelial cells (ECs) by binding vascular cell adhesion molecule-1 (VCAM-1);and (3) deficiency of CD11c in obese mice reduces atherosclerosis and decreases AT inflammation...
  5. Chemical Biology Studies of 3-Iodothyronamine and Related Thyroid Hormone Metabol
    THOMAS STERLING SCANLAN; Fiscal Year: 2013
    ..We recently demonstrated that chronic administration of low doses of T1AM inhibit feeding behavior in obese mice;i.e. like leptin, T1AM appears to act as an endogenous anorectic agent...
  6. Novel Small Molecule Therapeutics to Treat Obesity
    SUSAN MEDGHALCHI; Fiscal Year: 2010
    ..research, FASgen has developed the first pharmacological GPAT inhibitors which are efficacious in diet-induced obese mice. FASgen has synthesized series of GPAT inhibitors encompassing multiple chemical scaffolds...
  7. Effect of bisphenol A exposure on mammary stem cell function and transformation
    Luzhe Sun; Fiscal Year: 2013
    ..Third, the effect of BPA treatment on MaSC function of obese mice and marmosets will be examined...
  8. The Impact of Heat Shock Protein Expression on Inflammation and Insulin Action
    Andrea L Hevener; Fiscal Year: 2013
    ..These findings were recapitulated in genetically obese mice administered an HSF-1 co-inducer, BGP-15, which caused a marked increase in skeletal muscle HSP72 levels, ..
  9. Development of a mouse model of obesity in pregnancy
    Thomas Jansson; Fiscal Year: 2009
    ..that is relevant for the human condition, and (2) Identify the mechanisms underlying fetal overgrowth in obese mice. In both aims, female C57BL/6J mice will be fed either a control diet (11% of calories from fat) or a high fat ..
  10. The AMP-activated protein kinase (AMPK) antagonizes inflammation through SIRT1
    Hang Shi; Fiscal Year: 2012
    ..whether inactivation of AMPK in macrophages promotes inflammation and insulin resistance in diet-induced obese mice. We will perform bone marrow transplantation to generate mice with alpha1AMPK-deficient macrophages, and will ..
  11. The Role of PPAR Gamma in Fat-Resident Regulatory T Cells and Glucose Homeostasis
    SAGAR PRADEEP BAPAT; Fiscal Year: 2013
    ..Taken together, these studies will systematically characterize the role of PPAR! in fTregs and illuminate the role of fTregs in the pathogenesis of obesity-related type-2 diabetes. ..
  12. Development of New Therapeutics for Pancreatic Cancer Management
    RICHARD JOSEPH PIETRAS; Fiscal Year: 2013
    ..Discovery and validation of potent antitumor action and tolerability of metformin analogs in vivo may lead to timely clinical trials and possibly a significant breakthrough in pancreatic cancer therapy. ..
  13. MAP Kinase Phosphatase 3 (MKP-3) and Obesity-related Gluconeogenesis
    Haiyan Xu; Fiscal Year: 2013
    ..We demonstrated that expression of MKP-3 is elevated in the liver of obese mice and MKP-3 overexpression is sufficent to promote gluconeogenesis in hepatocytes and elevate fasting blood ..
  14. The Regulation of Mitochondrial Function by SIRT3
    Qiang Tong; Fiscal Year: 2010
    ..Interestingly, SIRT3 is down regulated in the brown adipose tissue of several genetically obese mice. Our yeast two- hybrid screening of SIRT3 identified an interaction with a subunit of the complex I of the ..
  15. Interleukin-10 and Regulation of Skeletal Muscle Insulin Action
    Jason K Kim; Fiscal Year: 2012
    ..Our findings will provide important insights into the role of obesity and inflammation in insulin resistance and further identify novel therapeutic targets in the treatment of type 2 diabetes. ..
  16. Preoptic histamine signaling in thermoregulation and energy expenditure
    IUSTIN VIRGIL TABAREAN; Fiscal Year: 2012
    ..Furthermore, leptin-deficient (ob/ob) and leptin receptor- defective (db/db) obese mice display lowered hypothalamic histamine concentrations...
  17. Rev-ERBa Regulates Mitochondrial Biogenesis, Adiposity, and Insulin Action
    Thomas H Reynolds; Fiscal Year: 2010
    ..By treating obese mice with the manganese tetrakis benzoic acid (MnTBA) porphyrin, we have identified heme's nuclear receptor, Rev-..
  18. Metabolic effects of adipose lipogenesis
    Timothy E McGraw; Fiscal Year: 2013
    ..However, knocking down the elevated ChREBP expression in liver of obese mice improves insulin sensitivity and metabolic syndrome...
  19. Impact of obesity on airway responses to air pollution
    Stephanie A Shore; Fiscal Year: 2013
    ..We have established that obese mice obese mice can serve as a useful model for such studies...
  20. Free Radical Mechanism in Obesity Potentiation of Environmental Hepatotoxicity
    Saurabh Chatterjee; Fiscal Year: 2013
    ..that low hepatotoxin exposure from the environment can potentiate the risk of progression of steatohepatitis in obese mice. The hypothesis will be tested in three specific aims that include investigating the mechanism of free radical ..
  21. Regulation of cholesterol catabolism by bile acids
    Jongsook Kim Kemper; Fiscal Year: 2013
    ..These studies will elucidate how SHP epigenetically controls BA-regulated hepatic functions, and identify novel potential diagnostic and/or therapeutic targets for metabolic diseases. ..
  22. Role of Perilipin in Hepatic Steatosis and Metabolism
    Thomas A Bowman; Fiscal Year: 2013
    ..abundantly expressed in human hepatocytes within steatotic livers it is not expressed within steatotic livers of obese mice. Preliminary data from our laboratory confirm this finding, and also that ectopic expression of perilipin in ..
  23. Obesity, Biomechanics, and Inflammation in Osteoarthritis
    Farshid Guilak; Fiscal Year: 2013
    ..OA in a leptin-receptor deficient mouse (db/db), and we will also measure osteoarthritic changes in diet-induced obese mice fed high-fat diets high in saturated and monounsaturated fatty acids, or omega-3 or omega-6 poly-unsaturated ..
  24. Affinity Tagging of Adipocyte Nuclei to Examine Epigenetic Controls in Obesity
    Richard Brian Meagher; Fiscal Year: 2013
    ..Affinity tagged adipocyte nuclei from different tissues of normal or environmentally compromised mice or obese mice may then be purified from mixed tissue samples on Streptavidin magnetic affinity resin...
  25. Melanocortin-4 Receptor-dependent regulation of energy balance after gastric bypa
    Vincent Aguirre; Fiscal Year: 2013
    ..We have developed a technique to perform RYGB, the most commonly performed bariatric procedure in the US, on obese mice to understand how it so effectively induces weight loss and improves diabetes...
  26. T Cells, Macrophages, Chemokines, and Adiposopathy in Diet-Induced Obesity
    CHRISTIE MITCHELL BALLANTYNE; Fiscal Year: 2013
    ..Both ?? T cells and ?? T cells are resident in adipose tissue of lean mice. Compared with lean mice, obese mice have a significant increase in ?? T cells but not in ?? T cells in adipose tissue...
  27. Regulation and Function of Adiponectin Oligomerization
    Feng Liu; Fiscal Year: 2012
    ..we found that GST-kappa is highly expressed in adipose tissue and the expression of GST-kappa is reduced in obese mice and human subjects and by TNF1a-treatment, and is induced by troglitazone...
  28. Modulation of PPAR-gamma phosphorylation at S273 regulates insulin sensitivity
    ALEXANDER BANKS; Fiscal Year: 2013
    ..will examine body composition, glucose homeostasis and PPAR-gamma target gene expression in adipose tissue from obese mice. We will compare the metabolic and transcriptional consequences of treating wild type Cdk5 KO mice treated with ..
  29. Targeting NAD Metabolism to Improve Glucose Homeostasis in Obesity and Aging
    Joseph A Baur; Fiscal Year: 2013
    ..It was recently shown that NAD levels fall substantially in the tissues of aged or obese mice. We hypothesize that this limits the activity of NAD-dependent enzymes, such as the deacetylase SIRT1, which has ..
  30. Dietary nitrate activation of PPARgamma improves insulin sensitivity
    MARK THOMAS contact GLADWIN; Fiscal Year: 2010
    ..glucose tolerance tests and hyperinsulinemic euglycemic clamps in chronically catheterized wild type and obese mice. Detailed mechanistic understanding will be obtained, using a targeted biochemical approach, regarding how ..
  31. Nicotinamide N-methyltransferase (NNMT) in obesity and insulin resistance
    Qin Yang; Fiscal Year: 2013
    ..The project will determine the critical role of NNMT in the development of obesity and type 2 diabetes. Potentially NNMT could be a new therapeutic target to prevent and treat obesity and type 2 diabetes. ..
  32. Targeting the Obesity-Inflammation-COX-Aromatase Axis to Lower Breast Cancer Risk
    ANDREW JESS DANNENBERG; Fiscal Year: 2013
    ..combined with a COX-2 inhibitor, suppress inflammation and reduce aromatase levels in vivo in the MG and VF of obese mice. If either a pharmacological or dietary approach disrupts the obesity->inflammation->COX->aromatase ..
  33. Macrophage Mitochondrial Stress in Inflammation, Insulin Resistance &Obesity
    LIZA MAKOWSKI HAYES; Fiscal Year: 2012
    ..The outcomes of this project will have a dramatic impact on the field of obesity research because little is known about mitochondrial metabolism in the MP. ..
  34. Cardiac metabolism and heart failure
    Rong Tian; Fiscal Year: 2010
    ..Results from the study will provide a basis for optimizing cardiac metabolism as part of the treatment strategy for heart failure. This is particularly important for patients with metabolic disorders such as obesity or diabetes. ..
  35. Therapeutic Opportunities of Targeting Tissue Factor Signaling in Obesity
    Fahumiya Samad; Fiscal Year: 2013
    ..We show that TF and PAR2 are co expressed in adipose tissues (AT) and elevated in adipose tissues of HFD-induced obese mice. Moreover, mice lacking the cytoplasmic domain of TF (TF4CT mice) or PAR2 are protected from HFD- induced ..
  36. PARASYMPATHETIC DYSFUNCTION IN OBESITY: EFFECT OF CHOLESTEROL ON VAChT
    Yifan Li; Fiscal Year: 2013
    ..In high fat diet (HFD)-induced obese mice, VAChT ubiquitination is reduced, along with the attenuated PSNS regulation of the heart...
  37. RBP4, Inflammation, and Insulin Resistance
    JULIE ELIZABETH NORSEEN; Fiscal Year: 2012
    ..Serum RBP4 levels will be lowered in obese mice to determine if elevated serum RBP4 levels are necessary for obesity-induced adipose tissue inflammation...
  38. A female-specific neuroendocrine center controlling energy expenditure
    STEPHANIE CORREA; Fiscal Year: 2013
    ..physical activity and determine if they are sufficient to rescue sedentary behavior when transplanted into obese mice. Impact: Nkx2-1Sf1Cre mice offer a unique opportunity to define a sexually dimorphic neuroendocrine center that ..
  39. Redox Regulation of p21ras in Angiogenesis
    Richard A Cohen; Fiscal Year: 2013
    ..Results of these studies in EC in culture will be relevant for our studies in obese mice fed a high fat, high sucrose (HFHS) diet in which we find angiogenesis to be impaired...
  40. Tissue specific production of RBP4 and mechanism of insulin resistance
    Timothy E Graham; Fiscal Year: 2013
    ..human subjects, and our preliminary data demonstrate a similar increase of apo-RBP4 in insulin resistant obese mice. Because apo-RBP4 is defined simply as the fraction of RBP4 not bound to retinol, it remains possible that apo-..
  41. Identification and molecular characterization of anti-diabetic flavonoids
    Dongmin Liu; Fiscal Year: 2013
    ..while kaempferol, a flavonol present in gingko biloba, improves insulin sensitivity and glucose homeostasis in obese mice. Notably, genistein in combination with kaempferol produces a potent additive effect on blood glycemic control ..
  42. Energetics &Breast Cancer: Obesity, Inflammation, Insulin Resistance &Risk
    Ruth E Patterson; Fiscal Year: 2013
    ..abstract_text> ..
  43. Investigating the Role of Adipocytes on Leukemia Relapse
    STEVEN DAVID MITTELMAN; Fiscal Year: 2013
    ..Therefore, we have developed mouse models of obesity and ALL. We have found that obese mice with ALL are more likely to relapse after treatment with vincristine, even when it is dosed proportional to body ..
  44. Mechanism of Cancer Prevention by Weight Control
    WEIQUN GEORGE WANG; Fiscal Year: 2011
    ..DCR;2) Assess whether selectively decreasing leptin but not IGF-1 levels by lipectomy in high fat diet-induced obese mice has inhibitory effects on mitogenic signaling cascades...
  45. Role of pancreatic neuropeptide Y in obesity and diabetes
    YUMI NONE IMAI; Fiscal Year: 2010
    ..The study has a potential to reveal a new mechanism to increase insulin secretion in obesity and prevent the development of diabetes in obesity. ..
  46. Apoptosis pathways underlying adipogenesis
    Niketa A Patel; Fiscal Year: 2013
    ..By showing that alternative splicing of apoptotic genes modulate differentiation and maturation of pre-adipocytes, the proposed studies will establish a new paradigm for adipogenesis and reveal new targets for treatment of obesity. ..
  47. A carboxypeptidase in the regulation of hypothalamic circuitry
    Sabrina Diano; Fiscal Year: 2013
    ..the following specific aims: Specific Aim 1) we will study PRCP and melanocortin peptides levels in lean and obese mice. Specific Aim 2) we will study leptin and ghrelin effects on PRCP...
  48. Cilial dysfunction and pathogenesis of obesity
    Bradley K Yoder; Fiscal Year: 2010
    ....
  49. Coordination of gut-liver bile acid signaling by FXR
    Jongsook Kim Kemper; Fiscal Year: 2013
    ..were substantially reduced, miR-34a levels were elevated, and FGF19-activated ERK signaling was defective in obese mice. Therefore, we hypothesize that FXR primes the liver for signaling by intestinal FGF19 both by transcriptionally ..
  50. Elucidation of the FGF21-Bmp8b Axis in the Regulation of Energy Balance
    Katie Colbert Coate; Fiscal Year: 2013
    ..this application indicate that FGF21 signaling in adipose tissue is required for its weight-lowering effects in obese mice. In addition, we found that bone morphogenetic protein 8b (Bmp8b) is the most highly induced gene in brown ..
  51. Studies of The Reciprocal Relationship Between Leptin and Fat
    Jeffrey M Friedman; Fiscal Year: 2013
    ..While leptin deficient obese mice show a massive increase in the number of fat cells, the factors regulating fat cell production are largely ..
  52. Myeloid cells, aging and the metabolic syndrome
    Richard M Ransohoff; Fiscal Year: 2013
    ..that selective deletion of MyD88 from myeloid cells virtually eliminated diet-induced metabolic syndrome in obese mice. Here we extend this research to effects of inflammatory signaling for age-related cognitive decline in aging ..
  53. Transcriptional Control of Macrophage in Atherogenesis
    Ajay Chawla; Fiscal Year: 2013
    ..how PPAR gamma and delta control the maturation of monocytes and activation of macrophages in lean and obese mice. Data from these studies will greatly enhance the molecular understanding of how PPAR gamma and delta regulate ..
  54. FoxO1 signaling in pituitary gonadotropes
    Danalea Skarra; Fiscal Year: 2013
    ..of insulin on FOXO1 phosphorylation and subcellular localization in pituitaries from lean and diet-induced obese mice. Results from this proposal have the potential to identify mechanisms of infertility related to PCOS and obesity ..
  55. The anti-inflammatory mRNA-binding protein ZFP36 in Obesity and Metabolism
    CALEB BENJAMIN KALLEN; Fiscal Year: 2013
    ..Our mouse model systems will test the effects of high ZFP36 expression in diet-induced obese mice and in mice that develop atherosclerosis...
  56. Aortic Stiffness and Hypertension in Obese Mice
    Richard A Cohen; Fiscal Year: 2013
    ....
  57. Metagenomic Studies of the Gut Microbiomes of Obese and Lean Twins
    JEFFREY IVAN GORDON; Fiscal Year: 2013
    ..a dynamic linkage between adiposity and gut microbial ecology, and provided evidence that the gut microbiota of obese mice is more efficient at harvesting energy than the microbiota of lean animals...
  58. Immunopathogenesis of Non-alcoholic Fatty Liver Disease
    Senad Divanovic; Fiscal Year: 2013
    ..that robustly upregulates IL-17 production by intestinal T cells, exacerbates hepatocellular damage in obese mice- whereas vancomycin- mediated depletion of SFB significantly reduces hepatocellular damage in such mice;and (e) ..
  59. A novel neuropeptide system involved in drug abuse
    Olivier Civelli; Fiscal Year: 2013
    ..It had not attracted much attention in research until 1995, when it was shown to be induced in genetically obese mice and to be able to increase food intake when injected intracerebroventrically...
  60. Breast cancer health disparity:mammary fat tissue and tumor macrophages interpla
    Marta Torroella-Kouri; Fiscal Year: 2012
    ..leptin-signaling inhibitor peptide designed by one of us will be used in in vivo experiments with diet-induced obese mice to reverse primary tumor and metastasis progression and macrophage recruitment in these animals implanted with ..
  61. Obesity and Environmental Lung Disease: The Role of Chemerin
    RICHARD ALAN JOHNSTON; Fiscal Year: 2013
    ..airway responsiveness to methacholine and increased pulmonary inflammation induced by exposure to O3 in obese mice through the use of a neutralizing antibody against chemerin...
  62. Mechanistic studies on obesity-deteriorated glucose and lipid metabolisms
    Chi Bun Chan; Fiscal Year: 2013
    ..interaction is a metabolically regulated process as less IR/PIKE-A complex is founded in the skeletal muscle of obese mice and lipid-stimulated myotubes...
  63. Novel Puerarin Analogs with Anti-Diabetic Activity
    NICHOLAS CAIRNS; Fiscal Year: 2007
    ..perform preliminary testing of the most potent lead compounds for their ability to improve glucose tolerance in obese mice. There are three specific aims in this phase 1 proposal: 1...
  64. GENE THERAPY, OBESITY AND HYPOTHALAMIC SIGNALING
    Satya Kalra; Fiscal Year: 2005
    ..that (1) lack leptin (ob/ob mice) and (2) display resistance to peripheral and not central leptin (New Zealand obese mice); and (3) lack NPY (-/-) and display obesity when maintained on HE diet...
  65. FATTY ACID ALPHA OXIDATION IN ADIPOCYTES
    Xiong Su; Fiscal Year: 2010
    ..b>Obese mice (ob/ob and db/db), mice resistant to diet induced obesity (CD36 null and SCD-1 null) and mice of different ages ..
  66. EXTRACELLULAR MATERIALS AND EMBRYONIC ORGAN FORMATION
    Merton Bernfield; Fiscal Year: 2002
    ..The transgenic mice mimic (i) obese mice with abnormalities in melanocortin-4 receptor function and (ii) humans with the Bardet-Biedl syndrome, a genetic ..