Lepr

Summary

Gene Symbol: Lepr
Description: leptin receptor
Alias: LEPROT, Leprb, Modb1, OB-RGRP, Obr, diabetes, obese-like, obl, leptin receptor, B219, LEP-R, OB receptor, leptin receptor gene-related protein
Species: mouse
Products:     Lepr

Top Publications

  1. Hoggard N, Mercer J, Rayner D, Moar K, Trayhurn P, Williams L. Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization. Biochem Biophys Res Commun. 1997;232:383-7 pubmed
    Expression of leptin receptor splice variants, including the long form variant (Ob-Rb), has been examined in murine peripheral tissues...
  2. DeFalco J, Tomishima M, Liu H, Zhao C, Cai X, Marth J, et al. Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus. Science. 2001;291:2608-13 pubmed
    ..into the arcuate nucleus of mice that express Cre only in those neurons that express neuropeptide Y or the leptin receptor. Sectioning of the brains revealed that these neurons receive inputs from neurons in other regions of the ..
  3. 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
  4. Hamilton R, Bhattacharya A, Walsh M, Shi Y, Wei R, Zhang Y, et al. Elevated protein carbonylation, and misfolding in sciatic nerve from db/db and Sod1(-/-) mice: plausible link between oxidative stress and demyelination. PLoS ONE. 2013;8:e65725 pubmed publisher
    ..We chose two distinct models to test our hypothesis: 1) the leptin receptor deficient mouse (dbdb) model of diabetic polyneuropathy and 2) superoxide dismutase 1 knockout (Sod1(-/-) ) ..
  5. Do O, Low J, Gaisano H, Thorn P. The secretory deficit in islets from db/db mice is mainly due to a loss of responding beta cells. Diabetologia. 2014;57:1400-9 pubmed publisher
    ..Within the db/db islets, changes were manifest as both a reduction in responding cells and a reduction in fusing insulin granules per cell. ..
  6. Bogdanov P, Corraliza L, Villena J, Carvalho A, Garcia Arumi J, Ramos D, et al. The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration. PLoS ONE. 2014;9:e97302 pubmed publisher
    ..the sequential events that are taking place in retinal neurodegeneration in a murine model of spontaneous type 2 diabetes (db/db mouse)...
  7. Terami N, Ogawa D, Tachibana H, Hatanaka T, Wada J, Nakatsuka A, et al. Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. PLoS ONE. 2014;9:e100777 pubmed publisher
    Inhibition of sodium glucose cotransporter 2 (SGLT2) has been reported as a new therapeutic strategy for treating diabetes. However, the effect of SGLT2 inhibitors on the kidney is unknown...
  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
    Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions...
  9. Goforth P, Leinninger G, Patterson C, Satin L, Myers M. Leptin acts via lateral hypothalamic area neurotensin neurons to inhibit orexin neurons by multiple GABA-independent mechanisms. J Neurosci. 2014;34:11405-15 pubmed publisher
    ..Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRb(Nts)) neurons lie in close apposition with OX ..
  10. Martinez Botas J, Anderson J, Tessier D, Lapillonne A, Chang B, Quast M, et al. Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice. Nat Genet. 2000;26:474-9 pubmed
    ..Our results demonstrate a role for perilipin in reining in basal HSL activity and regulating lipolysis and energy balance; thus, agents that inactivate perilipin may prove useful as anti-obesity medications. ..

Detail Information

Publications108 found, 100 shown here

  1. Hoggard N, Mercer J, Rayner D, Moar K, Trayhurn P, Williams L. Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization. Biochem Biophys Res Commun. 1997;232:383-7 pubmed
    Expression of leptin receptor splice variants, including the long form variant (Ob-Rb), has been examined in murine peripheral tissues...
  2. DeFalco J, Tomishima M, Liu H, Zhao C, Cai X, Marth J, et al. Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus. Science. 2001;291:2608-13 pubmed
    ..into the arcuate nucleus of mice that express Cre only in those neurons that express neuropeptide Y or the leptin receptor. Sectioning of the brains revealed that these neurons receive inputs from neurons in other regions of the ..
  3. 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
  4. Hamilton R, Bhattacharya A, Walsh M, Shi Y, Wei R, Zhang Y, et al. Elevated protein carbonylation, and misfolding in sciatic nerve from db/db and Sod1(-/-) mice: plausible link between oxidative stress and demyelination. PLoS ONE. 2013;8:e65725 pubmed publisher
    ..We chose two distinct models to test our hypothesis: 1) the leptin receptor deficient mouse (dbdb) model of diabetic polyneuropathy and 2) superoxide dismutase 1 knockout (Sod1(-/-) ) ..
  5. Do O, Low J, Gaisano H, Thorn P. The secretory deficit in islets from db/db mice is mainly due to a loss of responding beta cells. Diabetologia. 2014;57:1400-9 pubmed publisher
    ..Within the db/db islets, changes were manifest as both a reduction in responding cells and a reduction in fusing insulin granules per cell. ..
  6. Bogdanov P, Corraliza L, Villena J, Carvalho A, Garcia Arumi J, Ramos D, et al. The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration. PLoS ONE. 2014;9:e97302 pubmed publisher
    ..the sequential events that are taking place in retinal neurodegeneration in a murine model of spontaneous type 2 diabetes (db/db mouse)...
  7. Terami N, Ogawa D, Tachibana H, Hatanaka T, Wada J, Nakatsuka A, et al. Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. PLoS ONE. 2014;9:e100777 pubmed publisher
    Inhibition of sodium glucose cotransporter 2 (SGLT2) has been reported as a new therapeutic strategy for treating diabetes. However, the effect of SGLT2 inhibitors on the kidney is unknown...
  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
    Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions...
  9. Goforth P, Leinninger G, Patterson C, Satin L, Myers M. Leptin acts via lateral hypothalamic area neurotensin neurons to inhibit orexin neurons by multiple GABA-independent mechanisms. J Neurosci. 2014;34:11405-15 pubmed publisher
    ..Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRb(Nts)) neurons lie in close apposition with OX ..
  10. Martinez Botas J, Anderson J, Tessier D, Lapillonne A, Chang B, Quast M, et al. Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice. Nat Genet. 2000;26:474-9 pubmed
    ..Our results demonstrate a role for perilipin in reining in basal HSL activity and regulating lipolysis and energy balance; thus, agents that inactivate perilipin may prove useful as anti-obesity medications. ..
  11. O Connor J, Satpathy A, Hartman M, Horvath E, Kelley K, Dantzer R, et al. IL-1beta-mediated innate immunity is amplified in the db/db mouse model of type 2 diabetes. J Immunol. 2005;174:4991-7 pubmed
    Chronic inflammation appears to play a critical role in type 2 diabetes and its complications. Here we tested the hypothesis that this inflammatory dysregulation affects the IL-1beta system and has functional consequences in the brain...
  12. 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 adapt to acute cold ..
  13. Leinninger G, Opland D, Jo Y, Faouzi M, Christensen L, Cappellucci L, et al. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab. 2011;14:313-23 pubmed publisher
    Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear...
  14. Lord G, Matarese G, Howard J, Baker R, Bloom S, Lechler R. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897-901 pubmed
    ..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. De Luca C, Kowalski T, Zhang Y, Elmquist J, Lee C, Kilimann M, et al. Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J Clin Invest. 2005;115:3484-93 pubmed
    We have generated mice that carry a neuron-specific leptin receptor (LEPR) transgene whose expression is driven by the rat synapsin I promoter synapsin-LEPR B (SYN-LEPR-B)...
  16. Zhang L, Yan Liu D, Ma L, Luo Z, Cao T, Zhong J, et al. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. Circ Res. 2007;100:1063-70 pubmed
    ..We conclude that the activation of TRPV1 channels by capsaicin prevented adipogenesis and obesity. ..
  17. Wang L, Chopp M, Szalad A, Liu Z, Bolz M, Alvarez F, et al. Phosphodiesterase-5 is a therapeutic target for peripheral neuropathy in diabetic mice. Neuroscience. 2011;193:399-410 pubmed publisher
    Peripheral neuropathy is a common and major complication of diabetes, the underlying mechanisms of which are not fully understood...
  18. Gibbs E, Stock J, McCoid S, Stukenbrok H, Pessin J, Stevenson R, et al. Glycemic improvement in diabetic db/db mice by overexpression of the human insulin-regulatable glucose transporter (GLUT4). J Clin Invest. 1995;95:1512-8 pubmed
    ..muscle/fat glucose transporter) expression on glucose homeostasis in a genetic model of non-insulin-dependent diabetes mellitus were determined by expressing a human GLUT4 transgene (hGLUT4) in diabetic C57BL/KsJ-db/db mice...
  19. Loffreda S, Yang S, Lin H, Karp C, Brengman M, Wang D, et al. Leptin regulates proinflammatory immune responses. FASEB J. 1998;12:57-65 pubmed
    Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality...
  20. Plum L, Giesen K, Kluge R, Junger E, Linnartz K, Schurmann A, et al. Characterisation of the mouse diabetes susceptibilty locus Nidd/SJL: islet cell destruction, interaction with the obesity QTL Nob1, and effect of dietary fat. Diabetologia. 2002;45:823-30 pubmed
    The diabetes susceptibility locus Nidd/SJL was identified in an outcross of New Zealand obese (NZO) and lean Swiss/Jackson Laboratory mouse strain (SJL) mice...
  21. Ninichuk V, Khandoga A, Segerer S, Loetscher P, Schlapbach A, Revesz L, et al. The role of interstitial macrophages in nephropathy of type 2 diabetic db/db mice. Am J Pathol. 2007;170:1267-76 pubmed
    ..These data identify oral treatment with the CCR1 antagonist BL5923 as a potential therapy for late-stage diabetic nephropathy. ..
  22. Vernooy J, Bracke K, Drummen N, Pauwels N, Zabeau L, van Suylen R, et al. Leptin modulates innate and adaptive immune cell recruitment after cigarette smoke exposure in mice. J Immunol. 2010;184:7169-77 pubmed publisher
    ..in the onset of chronic obstructive pulmonary disease, we tested leptin-deficient ob/ob mice (C57BL/6), leptin receptor-deficient db/db mice (C57BKS), and littermates in a model of cigarette smoke (CS)-induced pulmonary ..
  23. Cheng H, Dauch J, Hayes J, Yanik B, Feldman E. Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities in painful neuropathy of type 2 diabetes. Neurobiol Dis. 2012;45:280-7 pubmed publisher
    Painful diabetic neuropathy (PDN) is a common, yet devastating complication of type 2 diabetes. At this time, there is no objective test for diagnosing PDN...
  24. Bjorbak C, Lavery H, Bates S, Olson R, Davis S, Flier J, et al. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem. 2000;275:40649-57 pubmed
    During leptin signaling, each of the phosphorylated tyrosine residues on the long form of the leptin receptor (LRb) mediates distinct signals...
  25. 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
    ..We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue. ..
  26. Gustavsson N, Larsson Nyrén G, Lindstrom P. Cell specificity of the cytoplasmic Ca2+ response to tolbutamide is impaired in beta-cells from hyperglycemic mice. J Endocrinol. 2006;190:461-70 pubmed
    ..The loss of temporal cell specificity for the response to tolbutamide in single beta-cells from hyperglycemic mice may be a sign of K(ATP)- or voltage-dependent calcium channel dysfunction. ..
  27. Saaristo A, Tammela T, Färkkilä A, Kärkkäinen M, Suominen E, Yla Herttuala S, et al. Vascular endothelial growth factor-C accelerates diabetic wound healing. Am J Pathol. 2006;169:1080-7 pubmed
    b>Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing, whereas the importance of lymphangiogenesis for wound healing is unclear...
  28. 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 ..
  29. Seo S, Guo D, Bugge K, Morgan D, Rahmouni K, Sheffield V. Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling. Hum Mol Genet. 2009;18:1323-31 pubmed publisher
    ..Here, we show that BBS proteins are required for leptin receptor (LepR) signaling in the hypothalamus...
  30. Lam D, Leinninger G, Louis G, Garfield A, Marston O, Leshan R, et al. Leptin does not directly affect CNS serotonin neurons to influence appetite. Cell Metab. 2011;13:584-91 pubmed publisher
    ..Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb...
  31. 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
    ..A leptin-dependent increase of SOCS-3 mRNA was seen in areas of hypothalamus expressing high levels of the leptin receptor long form. In mammalian cell lines, SOCS-3, but not CIS or SOCS-2, blocked leptin-induced signal transduction...
  32. Plum L, Kluge R, Giesen K, Altmuller J, Ortlepp J, Joost H. Type 2 diabetes-like hyperglycemia in a backcross model of NZO and SJL mice: characterization of a susceptibility locus on chromosome 4 and its relation with obesity. Diabetes. 2000;49:1590-6 pubmed
    ..SJL strain was established to locate genes responsible for obesity, insulin resistance, and type 2 diabetes-like hyperglycemia...
  33. Rahmouni K, Haynes W, Morgan D, Mark A. Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin. J Neurosci. 2003;23:5998-6004 pubmed
    ..of leptin, insulin, MC-3/4R agonist (MTII), and corticotrophin-releasing factor (CRF) on RSNA in leptin receptor-deficient (db/db) mice, MC-4R knock-out mice, and their wild-type controls...
  34. Eguchi J, Wada J, Hida K, Zhang H, Matsuoka T, Baba M, et al. Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity. Biochem J. 2005;387:343-53 pubmed
    ..in WATs (white adipose tissues) of OLETF (Otsuka Long-Evans Tokushima fatty) rats, an animal model for Type II diabetes and obesity...
  35. Liao Y, Ueno M, Nakagawa T, Huang C, Kanenishi K, Onodera M, et al. Oxidative damage in cerebral vessels of diabetic db/db mice. Diabetes Metab Res Rev. 2005;21:554-9 pubmed
    Oxidative stress in diabetes mellitus has recently received increasing attention as it has been proven to be associated with the development of diabetic vascular complications...
  36. Akpinar P, Kuwajima S, Krutzfeldt J, Stoffel M. Tmem27: a cleaved and shed plasma membrane protein that stimulates pancreatic beta cell proliferation. Cell Metab. 2005;2:385-97 pubmed
    ..Our results identify a pancreatic beta cell transmembrane protein that regulates cell growth of pancreatic islets. ..
  37. Brezniceanu M, Lau C, Godin N, Chenier I, Duclos A, Ethier J, et al. Reactive oxygen species promote caspase-12 expression and tubular apoptosis in diabetic nephropathy. J Am Soc Nephrol. 2010;21:943-54 pubmed publisher
    ..Taken together, these studies demonstrate that albuminuria may induce tubular apoptosis through generation of ROS and the subsequent expression and activation of endoplasmic reticulum stress genes in the diabetic kidney. ..
  38. Shimoda M, Kanda Y, Hamamoto S, Tawaramoto K, Hashiramoto M, Matsuki M, et al. The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes. Diabetologia. 2011;54:1098-108 pubmed publisher
    ..Liraglutide increases beta cell mass not only by directly regulating cell kinetics, but also by suppressing oxidative and ER stress, secondary to amelioration of glucolipotoxicity. ..
  39. Ellingsgaard H, Hauselmann I, Schuler B, Habib A, Baggio L, Meier D, et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011;17:1481-9 pubmed publisher
    Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion...
  40. 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
    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...
  41. Turner R, Kalra S, Wong C, Philbrick K, Lindenmaier L, Boghossian S, et al. Peripheral leptin regulates bone formation. J Bone Miner Res. 2013;28:22-34 pubmed publisher
    ..regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild-type (WT) mice, leptin receptor-deficient db/db mice, leptin-deficient ob/ob mice, and ob/ob mice treated with leptin...
  42. 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
    ..Moreover, ob/ob neuropeptide Y-/- mice, despite marked attenuation of diabetes and obesity phenotypes, showed no change in HDL cholesterol levels relative to ob/ob mice...
  43. Wang Q, Jiang L, Wang J, Li S, Yu Y, You J, et al. Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice. Hepatology. 2009;49:1166-75 pubmed publisher
    ..We found that in leptin receptor-deficient db/db mice, the expression of ACL was selectively elevated in the liver but not in the white ..
  44. 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
    ..Humans and mice lacking leptin or the leptin receptor (LepR) (ob/ob and db/db mice, respectively) are infertile and fail to enter puberty...
  45. Tartaglia L, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83:1263-71 pubmed
    ..library was prepared from mouse choroid plexus and screened with a leptin-AP fusion protein to identify a leptin receptor (OB-R)...
  46. Morioka T, Asilmaz E, Hu J, Dishinger J, Kurpad A, Elias C, et al. Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice. J Clin Invest. 2007;117:2860-8 pubmed
    ..disrupting leptin signaling in the pancreas on beta cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (..
  47. van de Wall E, Leshan R, Xu A, Balthasar N, Coppari R, Liu S, et al. Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion. Endocrinology. 2008;149:1773-85 pubmed
    ..By deleting the leptin receptor gene (Lepr) specifically in AgRP/NPY and/or POMC neurons of mice, we examined the several and combined ..
  48. Belmadani S, Palen D, Gonzalez Villalobos R, Boulares H, Matrougui K. Elevated epidermal growth factor receptor phosphorylation induces resistance artery dysfunction in diabetic db/db mice. Diabetes. 2008;57:1629-37 pubmed publisher
    ..Type 2 diabetes is associated with microvascular complications...
  49. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel D, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004;10:1384-9 pubmed
    Patients with diabetes and other obesity-linked conditions have increased susceptibility to cardiovascular disorders. The adipocytokine adiponectin is decreased in patients with obesity-linked diseases...
  50. Bates S, Dundon T, Seifert M, Carlson M, Maratos Flier E, Myers M. LRb-STAT3 signaling is required for the neuroendocrine regulation of energy expenditure by leptin. Diabetes. 2004;53:3067-73 pubmed
    ..tissue communicates body energy status to the neuroendocrine system by activating the long form of the leptin receptor (LRb)...
  51. Shi H, Sorrell J, Clegg D, Woods S, Seeley R. The roles of leptin receptors on POMC neurons in the regulation of sex-specific energy homeostasis. Physiol Behav. 2010;100:165-72 pubmed publisher
    Leptin regulates energy homeostasis and reproduction. One key population of leptin receptors (Lepr) are found on proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus, and evidence links the action of gonadal estrogens to ..
  52. Altarejos J, Goebel N, Conkright M, Inoue H, Xie J, Arias C, et al. The Creb1 coactivator Crtc1 is required for energy balance and fertility. Nat Med. 2008;14:1112-7 pubmed publisher
    ..Although disruption of Lepr-Stat3 signaling promotes obesity in mice, other features of Lepr function, such as fertility, seem normal, pointing ..
  53. Chen H, Charlat O, Tartaglia L, Woolf E, Weng X, Ellis S, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell. 1996;84:491-5 pubmed
  54. Leshan R, Björnholm M, Munzberg H, Myers M. Leptin receptor signaling and action in the central nervous system. Obesity (Silver Spring). 2006;14 Suppl 5:208S-212S pubmed
    ..Using "reporter" mice, in which LRb-expressing (long form of the leptin receptor) neurons express the histological marker, beta-galactosidase, coupled with the detection of LRb-mediated ..
  55. Piper M, Unger E, Myers M, Xu A. Specific physiological roles for signal transducer and activator of transcription 3 in leptin receptor-expressing neurons. Mol Endocrinol. 2008;22:751-9 pubmed
    ..Mice defective in leptin or its receptor [leptin receptor, isoform b (LepRb)] exhibit profound obesity, infertility, and reduced linear growth...
  56. Kim D, Nam B, Li J, Park J, Lee S, Kim D, et al. Translationally controlled tumour protein is associated with podocyte hypertrophy in a mouse model of type 1 diabetes. Diabetologia. 2012;55:1205-17 pubmed publisher
    ..As diabetes characteristically induces podocyte hypertrophy and mTORC1 has been implicated in this process, TCTP may have a ..
  57. Jacovetti C, Abderrahmani A, Parnaud G, Jonas J, Peyot M, Cornu M, et al. MicroRNAs contribute to compensatory ? cell expansion during pregnancy and obesity. J Clin Invest. 2012;122:3541-51 pubmed publisher
    ..for by an expansion of the functional ? cell mass that prevents chronic hyperglycemia and development of diabetes mellitus. The molecular basis underlying compensatory ? cell mass expansion is largely unknown...
  58. Hagberg C, Mehlem A, Falkevall A, Muhl L, Fam B, Ortsäter H, et al. Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. Nature. 2012;490:426-30 pubmed publisher
    The prevalence of type 2 diabetes is rapidly increasing, with severe socioeconomic impacts...
  59. Trayhurn P. Thermoregulation in the diabetic-obese (db/db) mouse. The role of non-shivering thermogenesis in energy balance. Pflugers Arch. 1979;380:227-32 pubmed
    ..of the ob/ob mouse, can be explained by a reduced energy expenditure on thermoregulatory thermogenesis; this may represent a primary mechanism for the operation of the "thirfty genotype" associated with obesity and diabetes.
  60. Zhang Y, Lee F, Barrera G, Lee H, Vales C, Gonzalez F, et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A. 2006;103:1006-11 pubmed
    ..In view of its central roles in coordinating regulation of both glucose and lipid metabolism, we propose that FXR agonists are promising therapeutic agents for treatment of diabetes mellitus.
  61. How O, Aasum E, Severson D, Chan W, Essop M, Larsen T. Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. Diabetes. 2006;55:466-73 pubmed
    Altered cardiac metabolism and function (diabetic cardiomyopathy) has been observed in diabetes. We hypothesize that cardiac efficiency, the ratio of cardiac work (pressure-volume area [PVA]) and myocardial oxygen consumption (MVo(2)), is ..
  62. Lemke U, Krones Herzig A, Berriel Diaz M, Narvekar P, Ziegler A, Vegiopoulos A, et al. The glucocorticoid receptor controls hepatic dyslipidemia through Hes1. Cell Metab. 2008;8:212-23 pubmed publisher
    ..steatosis) represents a hallmark of the metabolic syndrome and is tightly associated with obesity, type II diabetes, starvation, or glucocorticoid (GC) therapy...
  63. Leshan R, Louis G, Jo Y, Rhodes C, Munzberg H, Myers M. Direct innervation of GnRH neurons by metabolic- and sexual odorant-sensing leptin receptor neurons in the hypothalamic ventral premammillary nucleus. J Neurosci. 2009;29:3138-47 pubmed publisher
    Leptin acts via its receptor (LepRb) on specific CNS neurons to signal the adequacy of long-term energy stores, thereby permitting the expenditure of resources on energy-intensive processes such as reproduction...
  64. Ding H, Howarth A, Pannirselvam M, Anderson T, Severson D, Wiehler W, et al. Endothelial dysfunction in Type 2 diabetes correlates with deregulated expression of the tail-anchored membrane protein SLMAP. Am J Physiol Heart Circ Physiol. 2005;289:H206-11 pubmed
    ..Thus changes in SLMAP expression may be an important indicator for microvascular disease associated with Type 2 diabetes.
  65. Chu K, Lau T, Carlsson P, Leung P. Angiotensin II type 1 receptor blockade improves beta-cell function and glucose tolerance in a mouse model of type 2 diabetes. Diabetes. 2006;55:367-74 pubmed
    ..the hypothesis that there is a change in AT1R expression in the pancreatic islets of the obesity-induced type 2 diabetes model, the db/db mouse, which enables endogenous levels of angiotensin II to impair islet function...
  66. Wang Y, Heilig K, Saunders T, Minto A, Deb D, Chang A, et al. Transgenic overexpression of GLUT1 in mouse glomeruli produces renal disease resembling diabetic glomerulosclerosis. Am J Physiol Renal Physiol. 2010;299:F99-F111 pubmed publisher
    Previous work identified an important role for hyperglycemia in diabetic nephropathy (The Diabetes Control and Complications Trial Research Group. N Engl J Med 329: 977-986, 1993; UK Prospective Diabetes Study Group...
  67. Faggioni R, Fuller J, Moser A, Feingold K, Grunfeld C. LPS-induced anorexia in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice. Am J Physiol. 1997;273:R181-6 pubmed
    ..To further investigate the role of leptin in the LPS-induced anorexia, we administered LPS to leptin receptor-deficient (db/db) and leptin-deficient (ob/ob) mice...
  68. Hileman S, Pierroz D, Masuzaki H, Bjørbaek C, El Haschimi K, Banks W, et al. Characterizaton of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity. Endocrinology. 2002;143:775-83 pubmed
    ..unknown, but may involve reduced leptin transport across the blood-brain barrier via short isoforms of the leptin receptor (Ob-R)...
  69. Wysocki J, Ye M, Soler M, Gurley S, Xiao H, Bernstein K, et al. ACE and ACE2 activity in diabetic mice. Diabetes. 2006;55:2132-9 pubmed
    ..Alterations in renal ACE and ACE2 expression have been described in experimental models of diabetes, but ACE2 activity was not assessed in previous studies...
  70. Kosugi T, Nakayama T, Heinig M, Zhang L, Yuzawa Y, Sanchez Lozada L, et al. Effect of lowering uric acid on renal disease in the type 2 diabetic db/db mice. Am J Physiol Renal Physiol. 2009;297:F481-8 pubmed publisher
    ..In conclusion, hyperuricemia has a pathogenic role in the mild tubulointerstitial injury associated with diabetic nephropathy but not glomerular damage in db/db mice. Lowering uric acid may reduce tubulointerstitial injury in diabetes.
  71. Taylor K, Mills R, Costanzo A, Jameson J. Gammadelta T cells are reduced and rendered unresponsive by hyperglycemia and chronic TNFalpha in mouse models of obesity and metabolic disease. PLoS ONE. 2010;5:e11422 pubmed publisher
    ..Thus, metabolic disease negatively impacts homeostasis and functionality of skin gammadelta T cells, rendering host defense mechanisms vulnerable to injury and infection. ..
  72. Louis G, Leinninger G, Rhodes C, Myers M. Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons. J Neurosci. 2010;30:11278-87 pubmed publisher
    Leptin, the adipose-derived hormonal signal of body energy stores, acts via the leptin receptor (LepRb) on neurons in multiple brain regions...
  73. Ninomiya Y, Sako N, Imai Y. Enhanced gustatory neural responses to sugars in the diabetic db/db mouse. Am J Physiol. 1995;269:R930-7 pubmed
    Sweet taste sensitivity in a genetic model of diabetes, the db/db mouse, in which a single major gene defect leads to the expression of diabetes and obesity, was studied by examining chorda tympani nerve responses to various taste stimuli,..
  74. Uchida T, Nakamura T, Hashimoto N, Matsuda T, Kotani K, Sakaue H, et al. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat Med. 2005;11:175-82 pubmed
    ..beta cells in mice that lack either insulin receptor substrate 2 (Irs2(-/-)) or the long form of the leptin receptor (Lepr(-/-) or db/db)...
  75. Kieffer T, Heller R, Habener J. Leptin receptors expressed on pancreatic beta-cells. Biochem Biophys Res Commun. 1996;224:522-7 pubmed
    ..We demonstrate the expression of leptin receptor mRNA in primary rat pancreatic islets and in the insulinoma cell line beta TC-3...
  76. 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
    ..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. ..
  77. Ikejima S, Sasaki S, Sashinami H, Mori F, Ogawa Y, Nakamura T, et al. Impairment of host resistance to Listeria monocytogenes infection in liver of db/db and ob/ob mice. Diabetes. 2005;54:182-9 pubmed
    ..We investigated a role of leptin in Listeria monocytogenes infection using leptin receptor-deficient db/db mice and leptin-deficient ob/ob mice. These mutant mice were highly susceptible to L...
  78. Mancour L, Daghestani H, Dutta S, Westfield G, Schilling J, Oleskie A, et al. Ligand-induced architecture of the leptin receptor signaling complex. Mol Cell. 2012;48:655-61 pubmed publisher
    ..impact of leptin signaling on metabolism and body weight, little is known about the structure of the liganded leptin receptor (LEP-R) complex...
  79. Cohen P, Zhao C, Cai X, Montez J, Rohani S, Feinstein P, et al. Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest. 2001;108:1113-21 pubmed
    Animals with mutations in the leptin receptor (ObR) exhibit an obese phenotype that is indistinguishable from that of leptin deficient ob/ob mice...
  80. Altomonte J, Cong L, Harbaran S, Richter A, Xu J, Meseck M, et al. Foxo1 mediates insulin action on apoC-III and triglyceride metabolism. J Clin Invest. 2004;114:1493-503 pubmed
  81. Munzberg H, Jobst E, Bates S, Jones J, Villanueva E, Leshan R, et al. Appropriate inhibition of orexigenic hypothalamic arcuate nucleus neurons independently of leptin receptor/STAT3 signaling. J Neurosci. 2007;27:69-74 pubmed
    ..CFLIR) as a marker of ARC neuronal activity in db/db mice devoid of the signaling form of the leptin receptor (LRb) and s/s mice that express LRb(S1138) [which is defective for STAT3 (signal transducer and activator of ..
  82. Zhang H, Zhang J, Ungvari Z, Zhang C. Resveratrol improves endothelial function: role of TNF{alpha} and vascular oxidative stress. Arterioscler Thromb Vasc Biol. 2009;29:1164-71 pubmed publisher
    Oxidative stress plays an important role in type 2 diabetes-related endothelial dysfunction...
  83. Kanda Y, Shimoda M, Hamamoto S, Tawaramoto K, Kawasaki F, Hashiramoto M, et al. Molecular mechanism by which pioglitazone preserves pancreatic beta-cells in obese diabetic mice: evidence for acute and chronic actions as a PPARgamma agonist. Am J Physiol Endocrinol Metab. 2010;298:E278-86 pubmed publisher
  84. Chua S, Koutras I, Han L, Liu S, Kay J, Young S, et al. Fine structure of the murine leptin receptor gene: splice site suppression is required to form two alternatively spliced transcripts. Genomics. 1997;45:264-70 pubmed
    The fine structure of the murine leptin receptor gene (Lepr) is described. Duplicated ligand binding domains (conserved among cytokine receptors) are found in eight exons (coding exons 3 to 6 and 8 to 11)...
  85. Balthasar N, Coppari R, McMinn J, Liu S, Lee C, Tang V, et al. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron. 2004;42:983-91 pubmed
    ..In summary, leptin receptors on POMC neurons are required but not solely responsible for leptin's regulation of body weight homeostasis. ..
  86. Boudina S, Sena S, Theobald H, Sheng X, Wright J, Hu X, et al. Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes. 2007;56:2457-66 pubmed
    In obesity and diabetes, myocardial fatty acid utilization and myocardial oxygen consumption (MVo(2)) are increased, and cardiac efficiency is reduced...
  87. Banks A, Kon N, Knight C, Matsumoto M, Gutierrez Juarez R, Rossetti L, et al. SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab. 2008;8:333-41 pubmed publisher
    ..However, in various models of insulin resistance and diabetes, SirT1 transgenics display improved glucose tolerance due to decreased hepatic glucose production and increased ..
  88. Leibowitz M, Fievet C, Hennuyer N, Peinado Onsurbe J, Duez H, Bergera J, et al. Activation of PPARdelta alters lipid metabolism in db/db mice. FEBS Lett. 2000;473:333-6 pubmed
    ..These data suggest both that PPARdelta is involved in the regulation of cholesterol metabolism in db/db mice and that PPARdelta ligands could potentially have therapeutic value. ..
  89. Gómez Valadés A, Méndez Lucas A, Vidal Alabró A, Blasco F, Chillon M, Bartrons R, et al. Pck1 gene silencing in the liver improves glycemia control, insulin sensitivity, and dyslipidemia in db/db mice. Diabetes. 2008;57:2199-210 pubmed publisher
    ..The study assessed several clinical symptoms of diabetes and insulin signaling in peripheral tissues, in addition to changes in gene expression, protein, and metabolites ..
  90. Kang Y, Lee M, Song H, Ko G, Kwon O, Lim T, et al. CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic nephropathy in type 2 diabetic mice. Kidney Int. 2010;78:883-94 pubmed publisher
    ..Hence, our findings suggest that CCR2 antagonists can improve insulin resistance by modulation of the adipose tissue and restore renal function through both metabolic and anti-fibrotic effects in type 2 diabetic mice. ..