Lep

Summary

Gene Symbol: Lep
Description: leptin
Alias: obese, leptin, obesity factor
Species: mouse
Products:     Lep

Top Publications

  1. Seth R, Das S, Kumar A, Chanda A, Kadiiska M, Michelotti G, et al. CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8+ T cells aid progression of environment-linked nonalcoholic steatohepatitis. Toxicol Appl Pharmacol. 2014;274:42-54 pubmed publisher
    Environmental toxins induce a novel CYP2E1/leptin signaling axis in liver. This in turn activates a poorly characterized innate immune response that contributes to nonalcoholic steatohepatitis (NASH) progression...
  2. So J, Hur K, Tarrio M, Ruda V, Frank Kamenetsky M, Fitzgerald K, et al. Silencing of lipid metabolism genes through IRE1?-mediated mRNA decay lowers plasma lipids in mice. Cell Metab. 2012;16:487-99 pubmed publisher
    ..Ablation of XBP1 ameliorated hepatosteatosis, liver damage, and hypercholesterolemia in dyslipidemic animal models, suggesting that direct targeting of either IRE1? or XBP1 might be a feasible strategy to treat dyslipidemias. ..
  3. Tu Z, Keller M, Zhang C, Rabaglia M, Greenawalt D, Yang X, et al. Integrative analysis of a cross-loci regulation network identifies App as a gene regulating insulin secretion from pancreatic islets. PLoS Genet. 2012;8:e1003107 pubmed publisher
    ..mice from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mouse strains made genetically obese by the Leptin(ob/ob) mutation (Lep(ob))...
  4. Yu Y, Liu Y, Shi F, Zou H, Matarese G, La Cava A. Cutting edge: Leptin-induced ROR?t expression in CD4+ T cells promotes Th17 responses in systemic lupus erythematosus. J Immunol. 2013;190:3054-8 pubmed publisher
    ..we report that Th17 cell frequency is reduced in ob/ob mice (that are genetically deficient in the adipokine leptin) and that the administration of leptin to ob/ob mice restored Th17 cell numbers to values comparable to those ..
  5. Jansen H, van Essen P, Koenen T, Joosten L, Netea M, Tack C, et al. Autophagy activity is up-regulated in adipose tissue of obese individuals and modulates proinflammatory cytokine expression. Endocrinology. 2012;153:5866-74 pubmed publisher
    ..Levels of the autophagy marker LC3 were elevated in sc adipose tissue of obese vs...
  6. Peng X, Ju S, Fang F, Wang Y, Fang K, Cui X, et al. Comparison of brown and white adipose tissue fat fractions in ob, seipin, and Fsp27 gene knockout mice by chemical shift-selective imaging and (1)H-MR spectroscopy. Am J Physiol Endocrinol Metab. 2013;304:E160-7 pubmed publisher
    ..In addition, the differences in FFs in WAT and BAT measured by MR methods in different mouse models were related to the different regulation effects of ob, seipin, or Fsp27 gene on developing WAT and BAT. ..
  7. Lee J, Budanov A, Talukdar S, Park E, Park H, Park H, et al. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab. 2012;16:311-21 pubmed publisher
    ..by the Sesn2 locus, whose expression is induced upon hypernutrition--maintains metabolic homeostasis in liver of obese mice...
  8. Laque A, Zhang Y, Gettys S, Nguyen T, Bui K, Morrison C, et al. Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action. Am J Physiol Endocrinol Metab. 2013;304:E999-1011 pubmed publisher
    b>Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions...
  9. Procaccini C, De Rosa V, Galgani M, Carbone F, Cassano S, Greco D, et al. Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses. J Immunol. 2012;189:2941-53 pubmed publisher
    ..In this article, we show that leptin-induced activation of mTOR, which, in turn, controls leptin production and signaling, causes a defined cellular, ..
  10. Holland W, Adams A, Brozinick J, Bui H, Miyauchi Y, Kusminski C, et al. An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab. 2013;17:790-7 pubmed publisher
    ..rapidly and robustly stimulates adiponectin secretion in rodents while diminishing accumulation of ceramides in obese animals...

Detail Information

Publications100

  1. Seth R, Das S, Kumar A, Chanda A, Kadiiska M, Michelotti G, et al. CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8+ T cells aid progression of environment-linked nonalcoholic steatohepatitis. Toxicol Appl Pharmacol. 2014;274:42-54 pubmed publisher
    Environmental toxins induce a novel CYP2E1/leptin signaling axis in liver. This in turn activates a poorly characterized innate immune response that contributes to nonalcoholic steatohepatitis (NASH) progression...
  2. So J, Hur K, Tarrio M, Ruda V, Frank Kamenetsky M, Fitzgerald K, et al. Silencing of lipid metabolism genes through IRE1?-mediated mRNA decay lowers plasma lipids in mice. Cell Metab. 2012;16:487-99 pubmed publisher
    ..Ablation of XBP1 ameliorated hepatosteatosis, liver damage, and hypercholesterolemia in dyslipidemic animal models, suggesting that direct targeting of either IRE1? or XBP1 might be a feasible strategy to treat dyslipidemias. ..
  3. Tu Z, Keller M, Zhang C, Rabaglia M, Greenawalt D, Yang X, et al. Integrative analysis of a cross-loci regulation network identifies App as a gene regulating insulin secretion from pancreatic islets. PLoS Genet. 2012;8:e1003107 pubmed publisher
    ..mice from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mouse strains made genetically obese by the Leptin(ob/ob) mutation (Lep(ob))...
  4. Yu Y, Liu Y, Shi F, Zou H, Matarese G, La Cava A. Cutting edge: Leptin-induced ROR?t expression in CD4+ T cells promotes Th17 responses in systemic lupus erythematosus. J Immunol. 2013;190:3054-8 pubmed publisher
    ..we report that Th17 cell frequency is reduced in ob/ob mice (that are genetically deficient in the adipokine leptin) and that the administration of leptin to ob/ob mice restored Th17 cell numbers to values comparable to those ..
  5. Jansen H, van Essen P, Koenen T, Joosten L, Netea M, Tack C, et al. Autophagy activity is up-regulated in adipose tissue of obese individuals and modulates proinflammatory cytokine expression. Endocrinology. 2012;153:5866-74 pubmed publisher
    ..Levels of the autophagy marker LC3 were elevated in sc adipose tissue of obese vs...
  6. Peng X, Ju S, Fang F, Wang Y, Fang K, Cui X, et al. Comparison of brown and white adipose tissue fat fractions in ob, seipin, and Fsp27 gene knockout mice by chemical shift-selective imaging and (1)H-MR spectroscopy. Am J Physiol Endocrinol Metab. 2013;304:E160-7 pubmed publisher
    ..In addition, the differences in FFs in WAT and BAT measured by MR methods in different mouse models were related to the different regulation effects of ob, seipin, or Fsp27 gene on developing WAT and BAT. ..
  7. Lee J, Budanov A, Talukdar S, Park E, Park H, Park H, et al. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab. 2012;16:311-21 pubmed publisher
    ..by the Sesn2 locus, whose expression is induced upon hypernutrition--maintains metabolic homeostasis in liver of obese mice...
  8. Laque A, Zhang Y, Gettys S, Nguyen T, Bui K, Morrison C, et al. Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action. Am J Physiol Endocrinol Metab. 2013;304:E999-1011 pubmed publisher
    b>Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions...
  9. Procaccini C, De Rosa V, Galgani M, Carbone F, Cassano S, Greco D, et al. Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses. J Immunol. 2012;189:2941-53 pubmed publisher
    ..In this article, we show that leptin-induced activation of mTOR, which, in turn, controls leptin production and signaling, causes a defined cellular, ..
  10. Holland W, Adams A, Brozinick J, Bui H, Miyauchi Y, Kusminski C, et al. An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab. 2013;17:790-7 pubmed publisher
    ..rapidly and robustly stimulates adiponectin secretion in rodents while diminishing accumulation of ceramides in obese animals...
  11. Schroeter M, Eschholz N, Herzberg S, Jerchel I, Leifheit Nestler M, Czepluch F, et al. Leptin-dependent and leptin-independent paracrine effects of perivascular adipose tissue on neointima formation. Arterioscler Thromb Vasc Biol. 2013;33:980-7 pubmed publisher
    ..The aim of this study was to determine the role of perivascular leptin expression on neointima formation and to differentiate it from local inflammation and systemically elevated leptin ..
  12. Pajvani U, Qiang L, Kangsamaksin T, Kitajewski J, Ginsberg H, Accili D. Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability. Nat Med. 2013;19:1054-60 pubmed publisher
    ..These data identify Notch as a therapeutically actionable branch point of metabolic signaling at which Akt activation in the liver can be uncoupled from hepatosteatosis. ..
  13. Giordano A, Murano I, Mondini E, Perugini J, Smorlesi A, Severi I, et al. Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res. 2013;54:2423-36 pubmed publisher
    ..Here we present evidence that subcutaneous and visceral hypertrophic adipocytes of leptin-deficient (ob/ob and db/db) obese mice exhibit ultrastructural abnormalities (including calcium accumulation and ..
  14. Jiao Y, George S, Zhao Q, Hulver M, Hutson S, Bishop C, et al. Mex3c mutation reduces adiposity and increases energy expenditure. Mol Cell Biol. 2012;32:4350-62 pubmed publisher
    ..Mex3c was not detected in NPY or POMC neurons but was detected in leptin-responsive neurons in the ventromedial nucleus...
  15. Popescu I, Helleboid Chapman A, Lucas A, Vandewalle B, Dumont J, Bouchaert E, et al. The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity. FEBS Lett. 2010;584:2845-51 pubmed publisher
    ..FXR is predominantly cytosolic-localized in the islets of lean mice, but nuclear in obese mice...
  16. Bouret S, Draper S, Simerly R. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science. 2004;304:108-10 pubmed
    In adult mammals, the adipocyte-derived hormone leptin acts on the brain to reduce food intake by regulating the activity of neurons in the arcuate nucleus of the hypothalamus (ARH)...
  17. Toh S, Gong J, Du G, Li J, Yang S, Ye J, et al. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice. PLoS ONE. 2008;3:e2890 pubmed publisher
    ..tissue (BAT) and white adipose tissue (WAT) and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice...
  18. Watanabe M, Houten S, Wang L, Moschetta A, Mangelsdorf D, Heyman R, et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest. 2004;113:1408-18 pubmed
    ..These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia. ..
  19. Medina Gomez G, Gray S, Yetukuri L, Shimomura K, Virtue S, Campbell M, et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 2007;3:e64 pubmed
    ..Ablation of PPARg2 in the ob/ob background, PPARg2(-/-) Lep(ob)/Lep(ob) (POKO mouse), resulted in decreased fat mass, severe insulin resistance, beta-cell failure, and ..
  20. Erickson J, Hollopeter G, Palmiter R. Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science. 1996;274:1704-7 pubmed
    The obesity syndrome of ob/ob mice results from lack of leptin, a hormone released by fat cells that acts in the brain to suppress feeding and stimulate metabolism...
  21. Wolfgang M, Cha S, Sidhaye A, Chohnan S, Cline G, Shulman G, et al. Regulation of hypothalamic malonyl-CoA by central glucose and leptin. Proc Natl Acad Sci U S A. 2007;104:19285-90 pubmed
    ..intermediates in the malonyl-CoA pathway to metabolic and endocrine cues, notably those provoked by glucose and leptin. Hypothalamic malonyl-CoA rises in proportion to the carbohydrate content of the diet consumed after food ..
  22. Berglund E, Vianna C, Donato J, Kim M, Chuang J, Lee C, et al. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest. 2012;122:1000-9 pubmed publisher
    b>Leptin action on its receptor (LEPR) stimulates energy expenditure and reduces food intake, thereby lowering body weight. One leptin-sensitive target cell mediating these effects on energy balance is the proopiomelano-cortin (POMC) neuron...
  23. Gavrilova O, Leon L, Marcus Samuels B, Mason M, Castle A, Refetoff S, et al. Torpor in mice is induced by both leptin-dependent and -independent mechanisms. Proc Natl Acad Sci U S A. 1999;96:14623-8 pubmed
    We tested the effect of chronic leptin treatment on fasting-induced torpor in leptin-deficient A-ZIP/F-1 and ob/ob mice...
  24. Leshan R, Greenwald Yarnell M, Patterson C, Gonzalez I, Myers M. Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance. Nat Med. 2012;18:820-3 pubmed publisher
    ..b>Leptin, an adipocyte-derived hormone that signals the long-term status of bodily energy stores, acts through multiple ..
  25. Wang C, Stapleton D, Schueler K, Rabaglia M, Oler A, Keller M, et al. Tsc2, a positional candidate gene underlying a quantitative trait locus for hepatic steatosis. J Lipid Res. 2012;53:1493-501 pubmed publisher
    ..locus (QTL) for NAFLD to chromosome 17 in a cross between C57BL/6 (B6) and BTBR mouse strains made genetically obese with the Lep(ob/ob) mutation. We identified Tsc2 as a gene underlying the chromosome 17 NAFLD QTL...
  26. Donato J, Cravo R, Frazao R, Gautron L, Scott M, Lachey J, et al. Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons. J Clin Invest. 2011;121:355-68 pubmed publisher
    ..The adipocyte-derived hormone leptin is a key metabolic signal to the neuroendocrine reproductive axis...
  27. Gonzalez R, Cherfils S, Escobar M, Yoo J, Carino C, Styer A, et al. Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2). J Biol Chem. 2006;281:26320-8 pubmed
    To gain insight into the mechanism(s) by which leptin contributes to mammary tumor (MT) development we investigated the effects of leptin, kinase inhibitors, and/or leptin receptor antagonists (LPrA2) on 4T1 mouse mammary cancer cells in ..
  28. Silver D, Jiang X, Tall A. 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. J Biol Chem. 1999;274:4140-6 pubmed
    ..was to evaluate mechanisms responsible for increased HDL in ob/ob mice and to assess potential reversibility by leptin administration. ob/ob mice were found to have increased HDL cholesterol (2-fold), apoA-I (1...
  29. Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palu G, et al. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007;292:G518-25 pubmed
    ..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...
  30. Bouhidel O, Pons S, Souktani R, Zini R, Berdeaux A, Ghaleh B. Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice. Am J Physiol Heart Circ Physiol. 2008;295:H1580-6 pubmed publisher
    ..is a major risk factor of cardiovascular diseases, the effects of IPCD were investigated in 8- to 10-wk-old leptin-deficient obese (ob/ob) mice and compared with wild-type C57BL/6J (WT) mice...
  31. Steinberg G, Michell B, van Denderen B, Watt M, Carey A, Fam B, et al. Tumor necrosis factor alpha-induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling. Cell Metab. 2006;4:465-74 pubmed
    ..Our data demonstrate that AMPK is an important TNFalpha signaling target and is a contributing factor to the suppression of fatty-acid oxidation and the development of lipid-induced insulin resistance in obesity. ..
  32. Zhang C, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell. 2001;105:745-55 pubmed
    ..These results establish UCP2 as a key component of beta cell glucose sensing, and as a critical link between obesity, beta cell dysfunction, and type 2 diabetes. ..
  33. Di Marzo V, Goparaju S, Wang L, Liu J, Batkai S, Jarai Z, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410:822-5 pubmed
    b>Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance...
  34. Ghamari Langroudi M, Srisai D, Cone R. Multinodal regulation of the arcuate/paraventricular nucleus circuit by leptin. Proc Natl Acad Sci U S A. 2011;108:355-60 pubmed publisher
    ..Most studies suggest that leptin regulates PVN neurons indirectly, by binding to receptors in the arcuate nucleus or ventromedial hypothalamus and ..
  35. Minokoshi Y, Kim Y, Peroni O, Fryer L, Müller C, Carling D, et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002;415:339-43 pubmed
    b>Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function...
  36. Batra A, Okur B, Glauben R, Erben U, Ihbe J, Stroh T, et al. Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology. 2010;151:56-62 pubmed publisher
    Besides being mandatory in the metabolic system, adipokines like leptin directly affect immunity. Leptin was found to be necessary in T helper 1 (Th1)-dependent inflammatory processes, whereas effects on Th2 cells are rarely understood...
  37. Dong B, Saha P, Huang W, Chen W, Abu Elheiga L, Wakil S, et al. Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci U S A. 2009;106:18831-6 pubmed publisher
    ..Here we use leptin-deficient mice (ob/ob) and ob/ob, CAR(-/-) double mutant mice to identify a metabolic role of CAR in type 2 ..
  38. Henderson R, Hobbs J, Mathies M, Hogg N. Rapid recruitment of inflammatory monocytes is independent of neutrophil migration. Blood. 2003;102:328-35 pubmed
    ..The murine monocyte therefore responds rapidly to chemokines produced in situ by tissue cells at the site of inflammation with no requirement for prior influx of neutrophils. ..
  39. Gong Y, Ishida Takahashi R, Villanueva E, Fingar D, Munzberg H, Myers M. The long form of the leptin receptor regulates STAT5 and ribosomal protein S6 via alternate mechanisms. J Biol Chem. 2007;282:31019-27 pubmed
    The action of leptin via the long form of its receptor (LepRb) is central to the control of body energy homeostasis and neuroendocrine function, but the mechanisms by which LepRb regulates intracellular signaling have remained ..
  40. Park S, Zhou Y, Lee J, Lu A, Sun C, Chung J, et al. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. Nat Med. 2010;16:429-37 pubmed publisher
    ..Our results define a previously unknown insulin receptor signaling pathway and provide new mechanistic insight into the development of ER stress during obesity. ..
  41. Chiu C, Lin W, Huang S, Lee Y. Effect of a C/EBP gene replacement on mitochondrial biogenesis in fat cells. Genes Dev. 2004;18:1970-5 pubmed
    ..Galphas, when overexpressed in fat-laden 3T3-L1 cells, stimulated mitochondrial biogenesis similar to that seen in the WAT of beta/beta mice, and effectively diminished the stored lipid pool. ..
  42. Gautam D, Gavrilova O, Jeon J, Pack S, Jou W, Cui Y, et al. Beneficial metabolic effects of M3 muscarinic acetylcholine receptor deficiency. Cell Metab. 2006;4:363-75 pubmed
    ..These findings suggest that the M3 receptor may represent a potential pharmacologic target for the treatment of obesity and associated metabolic disorders. ..
  43. Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab. 2007;293:E1118-28 pubmed
    ..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...
  44. Huang J, Jia Y, Fu T, Viswakarma N, Bai L, Rao M, et al. Sustained activation of PPAR? by endogenous ligands increases hepatic fatty acid oxidation and prevents obesity in ob/ob mice. FASEB J. 2012;26:628-38 pubmed publisher
    Obesity, a major health concern, results from an imbalance between energy intake and expenditure. Leptin-deficient ob/ob mice are paradigmatic of obesity, resulting from excess energy intake and storage...
  45. Munzberg H, Flier J, Bjørbaek C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology. 2004;145:4880-9 pubmed
    b>Leptin resistance in diet-induced obese (DIO) mice is characterized by elevated serum leptin and a decreased response to exogenous leptin and is caused by unknown defects in the central nervous system...
  46. Vidal Puig A, Jimenez Linan M, Lowell B, Hamann A, Hu E, Spiegelman B, et al. Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. J Clin Invest. 1996;97:2553-61 pubmed
    ..Probes for detection of adipocyte P2, the obese gene product, leptin, and 18S mRNAs were also employed. Both gamma l and gamma 2 mRNAs were abundantly expressed in adipose tissue...
  47. Rahmouni K, Morgan D, Morgan G, Mark A, Haynes W. Role of selective leptin resistance in diet-induced obesity hypertension. Diabetes. 2005;54:2012-8 pubmed
    b>Leptin is an adipocyte-derived hormone that plays a key role in the regulation of body weight through its actions on appetite and metabolism. Leptin also increases sympathetic nerve activity (SNA) and blood pressure...
  48. Herberg L, Coleman D. Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism. 1977;26:59-99 pubmed
    ..The metabolic peculiarities can be due to a dominant gene, as for the yellow obese, or a single recessive gene, as in the obese and the diabetes mouse; or they can be of polygenic origin, as for ..
  49. Kumar K, Trevaskis J, Lam D, Sutton G, Koza R, Chouljenko V, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008;8:468-81 pubmed publisher
    ..3 months of HFD or with genetically induced obesity, suggesting an association with metabolic disorders in the obese state...
  50. Kondo T, Kahn C. Altered insulin signaling in retinal tissue in diabetic states. J Biol Chem. 2004;279:37997-8006 pubmed
    ..Furthermore, insulin signaling in retinal endothelial cells is differentially altered in diabetes and is also differentially regulated from insulin signaling in classical target tissues such as liver. ..
  51. Sugita H, Fujimoto M, Yasukawa T, Shimizu N, Sugita M, Yasuhara S, et al. Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem. 2005;280:14203-11 pubmed
    ..These findings indicate that iNOS reduces IRS-1 expression in skeletal muscle via proteasome-mediated degradation and thereby may contribute to obesity-related insulin resistance. ..
  52. Shimomura I, Hammer R, Ikemoto S, Brown M, Goldstein J. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401:73-6 pubmed
    ..tissue from these mice was markedly deficient in messenger RNAs encoding several fat-specific proteins, including leptin, a fat-derived hormone that regulates food intake and energy metabolism...
  53. Styer A, Sullivan B, Puder M, Arsenault D, Petrozza J, Serikawa T, et al. Ablation of leptin signaling disrupts the establishment, development, and maintenance of endometriosis-like lesions in a murine model. Endocrinology. 2008;149:506-14 pubmed
    b>Leptin, a 16-kDa cytokine, has been implicated in several reproductive processes and disorders...
  54. Shimomura I, Bashmakov Y, Horton J. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem. 1999;274:30028-32 pubmed
    ..In the current studies, we measured the content of SREBPs in livers from two mouse models of diabetes, obese ob/ob mice and transgenic aP2-SREBP-1c436 (aP2-SREBP-1c) mice that overexpress nuclear SREBP-1c only in adipose ..
  55. Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem. 2006;281:26602-14 pubmed
    ..We concluded that both paracrine and endocrine effects of MCP-1 may contribute to the development of insulin resistance in aP2-MCP-1 mice. ..
  56. Townsend K, Lorenzi M, Widmaier E. High-fat diet-induced changes in body mass and hypothalamic gene expression in wild-type and leptin-deficient mice. Endocrine. 2008;33:176-88 pubmed publisher
    ..obesity results from increased energy consumption, is associated with changes in expression of genes involved in leptin signal transduction, and is altered by hyperleptinemia...
  57. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker K, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111:305-17 pubmed
    We previously showed that leptin inhibits bone formation by an undefined mechanism...
  58. Gao H, Bryzgalova G, Hedman E, Khan A, Efendic S, Gustafsson J, et al. Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Mol Endocrinol. 2006;20:1287-99 pubmed
    ..We propose that this may be mediated, at least partially, via estrogen stimulation of the hepatic expression of Stat3, leading to decreased expression of hepatic lipogenic genes, and thereby to antidiabetic effects. ..
  59. Leclercq I, Farrell G, Schriemer R, Robertson G. Leptin is essential for the hepatic fibrogenic response to chronic liver injury. J Hepatol. 2002;37:206-13 pubmed
    ..The correlation between increased leptin, obesity and hepatic fibrosis prompted us to hypothesise that leptin has profibrogenic effects on the liver...
  60. Leinninger G, Jo Y, Leshan R, Louis G, Yang H, Barrera J, et al. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 2009;10:89-98 pubmed publisher
    ..The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely ..
  61. Ozcan L, Ergin A, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9:35-51 pubmed publisher
    b>Leptin has not evolved as a therapeutic modality for the treatment of obesity due to the prevalence of leptin resistance in a majority of the obese population...
  62. Muoio D, Dohm G, Tapscott E, Coleman R. Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob/ob mice. Am J Physiol. 1999;276:E913-21 pubmed
    Because muscle triacylglycerol (TAG) accumulation might contribute to insulin resistance in leptin-deficient ob/ob mice, we studied the acute (60- to 90-min) effects of leptin and insulin on [14C]glucose and [14C]oleate metabolism in ..
  63. Busso N, So A, Chobaz Péclat V, Morard C, Martinez Soria E, Talabot Ayer D, et al. Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J Immunol. 2002;168:875-82 pubmed
    b>Leptin is produced almost exclusively by adipocytes and regulates body weight at the hypothalamic level. In addition, recent studies showed that leptin plays an important role in T lymphocyte responses...
  64. Bates S, Stearns W, Dundon T, Schubert M, Tso A, Wang Y, et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature. 2003;421:856-9 pubmed
    Secretion of leptin from adipocytes communicates body energy status to the brain by activating the leptin receptor long form (LRb)...
  65. Zhang Y, Kerman I, Laque A, Nguyen P, Faouzi M, Louis G, et al. Leptin-receptor-expressing neurons in the dorsomedial hypothalamus and median preoptic area regulate sympathetic brown adipose tissue circuits. J Neurosci. 2011;31:1873-84 pubmed publisher
    ..Severely obese mice that lack leptin or its receptor (LepRb) show decreased BAT capacity, sympathetic tone, and body temperature and thus are unable to ..
  66. Koenen T, Stienstra R, van Tits L, de Graaf J, Stalenhoef A, Joosten L, et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue. Diabetes. 2011;60:517-24 pubmed publisher
    ..The concerted actions lead to enhanced secretion of IL-1? in adipose tissue that may contribute to the development of insulin resistance. ..
  67. Matsusue K, Kusakabe T, Noguchi T, Takiguchi S, Suzuki T, Yamano S, et al. Hepatic steatosis in leptin-deficient mice is promoted by the PPARgamma target gene Fsp27. Cell Metab. 2008;7:302-11 pubmed publisher
    Peroxisome proliferator-activated receptor gamma (PPARgamma) is induced in leptin-deficient (ob/ob) mouse liver and is critical for the development of hepatic steatosis...
  68. Cao L, Liu X, Lin E, Wang C, Choi E, Riban V, et al. Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition. Cell. 2010;142:52-64 pubmed publisher
    ..animals held in an enriched environment (EE) inhibited cancer proliferation in vitro and was markedly lower in leptin. Hypothalamic brain-derived neurotrophic factor (BDNF) was selectively upregulated by EE, and its genetic ..
  69. Kaiyala K, Morton G, Leroux B, Ogimoto K, Wisse B, Schwartz M. Identification of body fat mass as a major determinant of metabolic rate in mice. Diabetes. 2010;59:1657-66 pubmed publisher
    ..mass (LBM), 2) compared the independent contributions of LBM and fat mass (FM) to EE, and 3) investigated whether leptin contributes to the link between FM and EE...
  70. Coleman D. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia. 1978;14:141-8 pubmed
  71. Morton G, Kaiyala K, Fisher J, Ogimoto K, Schwartz M, Wisse B. Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice. Am J Physiol Endocrinol Metab. 2011;300:E392-401 pubmed publisher
    ..We evaluated ambulatory activity and wheel running in leptin-deficient ob/ob mice and in wild-type mice rendered hypoleptinemic by fasting in both the presence and absence of ..
  72. Villanueva E, Munzberg H, Cota D, Leshan R, Kopp K, Ishida Takahashi R, et al. Complex regulation of mammalian target of rapamycin complex 1 in the basomedial hypothalamus by leptin and nutritional status. Endocrinology. 2009;150:4541-51 pubmed publisher
    ..b>Leptin and feeding regulate the mammalian target of rapamycin complex 1 (mTORC1) in the hypothalamus, and hypothalamic ..
  73. Lumeng C, Bodzin J, Saltiel A. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175-84 pubmed
    ..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...
  74. Mazumder P, O Neill B, Roberts M, Buchanan J, Yun U, Cooksey R, et al. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes. 2004;53:2366-74 pubmed
    ..The goal of these studies was to determine whether the hearts of leptin-deficient 8-week-old ob/ob mice were able to modulate cardiac substrate utilization in response to insulin or to ..
  75. Atkinson L, Fischer M, Lopaschuk G. Leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis. J Biol Chem. 2002;277:29424-30 pubmed
    b>Leptin regulates fatty acid metabolism in liver, skeletal muscle, and pancreas by partitioning fatty acids into oxidation rather than triacylglycerol (TG) storage...
  76. Trayhurn P, Thurlby P, James W. Thermogenic defect in pre-obese ob/ob mice. Nature. 1977;266:60-2 pubmed
  77. Naveilhan P, Svensson L, Nystrom S, Ekstrand A, Ernfors P. Attenuation of hypercholesterolemia and hyperglycemia in ob/ob mice by NPY Y2 receptor ablation. Peptides. 2002;23:1087-91 pubmed
    ..It has previously been shown that the NPY Y2 receptor is required for a full biological response to leptin in the central nervous system...
  78. Shi H, Kokoeva M, Inouye K, Tzameli I, Yin H, Flier J. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006;116:3015-25 pubmed
    ..Inflammatory pathways are activated in tissues of obese animals and humans and play an important role in obesity-associated insulin resistance...
  79. Xu H, Barnes G, Yang Q, Tan G, Yang D, Chou C, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821-30 pubmed
    ..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...
  80. Korda M, Kubant R, Patton S, Malinski T. Leptin-induced endothelial dysfunction in obesity. Am J Physiol Heart Circ Physiol. 2008;295:H1514-21 pubmed publisher
    ..were placed near the surface (5+/-2 microm) of a single human umbilical vein endothelial cell (HUVEC) exposed to leptin or aortic endothelium of obese C57BL/6J mice, and concentrations of calcium ionophore (CaI)-stimulated NO, O(2)(-),..
  81. Yoon J, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature. 2001;413:131-8 pubmed
    ..These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver. ..
  82. Lee N, Sowa H, Hinoi E, Ferron M, Ahn J, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456-69 pubmed
    ..By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism. ..
  83. Mayer J, Bates M, Dickie M. Hereditary diabetes in genetically obese mice. Science. 1951;113:746-7 pubmed
  84. Delporte M, El Mkadem S, Quisquater M, Brichard S. Leptin treatment markedly increased plasma adiponectin but barely decreased plasma resistin of ob/ob mice. Am J Physiol Endocrinol Metab. 2004;287:E446-53 pubmed
    Adiponectin (ApN) and leptin are two adipocytokines that control fuel homeostasis, body weight, and insulin sensitivity. Their interplay is still poorly studied...
  85. Bjørbaek C, Elmquist J, Frantz J, Shoelson S, Flier J. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell. 1998;1:619-25 pubmed
    b>Leptin affects food intake and body weight by actions on the hypothalamus. Although leptin resistance is common in obesity, mechanisms have not been identified...
  86. Hiuge Shimizu A, Maeda N, Hirata A, Nakatsuji H, Nakamura K, Okuno A, et al. Dynamic changes of adiponectin and S100A8 levels by the selective peroxisome proliferator-activated receptor-gamma agonist rivoglitazone. Arterioscler Thromb Vasc Biol. 2011;31:792-9 pubmed publisher
    ..receptor-? agonist Rivo remarkably enhanced adiponectin in plasma and decreased adipose S100A8 mRNA levels in obese mice...
  87. Mark A, Shaffer R, Correia M, Morgan D, Sigmund C, Haynes W. Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice. J Hypertens. 1999;17:1949-53 pubmed
    ..ob/ob(Lep(ob)/Lep(ob)) mice have a mutation in the ob gene and are leptin-deficient...
  88. Commins S, Watson P, Padgett M, Dudley A, Argyropoulos G, Gettys T. Induction of uncoupling protein expression in brown and white adipose tissue by leptin. Endocrinology. 1999;140:292-300 pubmed
    ..In ob/ob mice, the absence of leptin affects both components of the energy balance equation, and the mice become morbidly obese after weaning...