Lep

Summary

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

Top Publications

  1. ncbi Weight-reducing effects of the plasma protein encoded by the obese gene
    J L Halaas
    Laboratory of Molecular Genetics, Howard Hughes Medical Institute, Rockfeller University, New York, NY 10021, USA
    Science 269:543-6. 1995
  2. 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
  3. 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
  4. ncbi Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects
    M Maffei
    Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10021, USA
    Nat Med 1:1155-61. 1995
  5. pmc A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure
    Vijay K Yadav
    Department of Genetics and Development, Columbia University, New York, NY 10032, USA
    Cell 138:976-89. 2009
  6. ncbi STAT3 signalling is required for leptin regulation of energy balance but not reproduction
    Sarah H Bates
    Research Division, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, Massachusetts 02215, USA
    Nature 421:856-9. 2003
  7. pmc Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals
    David Patsouris
    Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Cell Metab 8:301-9. 2008
  8. 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
  9. pmc Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes
    Kimihiko Matsusue
    Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Frederick, Maryland 20892, USA
    J Clin Invest 111:737-47. 2003
  10. 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

Research Grants

  1. Transport of neurotrophic cytokines after spinal cord injury
    Weihong Pan; Fiscal Year: 2007
  2. Transport of TNFalpha across the BBB
    Weihong Pan; Fiscal Year: 2008
  3. Conference on Obesity
    Michael Schwartz; Fiscal Year: 2003
  4. HYPOTHALAMIC PEPTIDES, FOOD INTAKE, AND DIABETES
    Michael Schwartz; Fiscal Year: 2006
  5. TRH in mediating the bradycardia of caloric restriction
    Steven Swoap; Fiscal Year: 2005
  6. Integration of Long- and Short-Term Control of Feeding
    Michael Schwartz; Fiscal Year: 2004
  7. Mentored Clinical Research Scholar Program at Iowa
    ALLYN MARK; Fiscal Year: 2007
  8. ApoB-Proteoglycan Interaction and Atherosclerosis
    Zhouji Chen; Fiscal Year: 2006
  9. Effect of Leptin on Trophoblast Invasiveness
    Laura Schulz; Fiscal Year: 2006
  10. Role of Leucine Metabolism in Leucine Signaling
    CHRISTOPHER JOHN LYNCH; Fiscal Year: 2010

Detail Information

Publications198 found, 100 shown here

  1. ncbi Weight-reducing effects of the plasma protein encoded by the obese gene
    J L Halaas
    Laboratory of Molecular Genetics, Howard Hughes Medical Institute, Rockfeller University, New York, NY 10021, USA
    Science 269:543-6. 1995
    ..2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores...
  2. 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
    C57BL/6J mice with a mutation in the obese (ob) gene are obese, diabetic, and exhibit reduced activity, metabolism, and body temperature...
  3. 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...
  4. ncbi Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects
    M Maffei
    Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10021, USA
    Nat Med 1:1155-61. 1995
    b>Leptin, the gene product of the obese gene, may play an important role in regulating body weight by signalling the size of the adipose tissue mass...
  5. pmc A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure
    Vijay K Yadav
    Department of Genetics and Development, Columbia University, New York, NY 10032, USA
    Cell 138:976-89. 2009
    b>Leptin inhibition of bone mass accrual requires the integrity of specific hypothalamic neurons but not expression of its receptor on these neurons. The same is true for its regulation of appetite and energy expenditure...
  6. ncbi STAT3 signalling is required for leptin regulation of energy balance but not reproduction
    Sarah H Bates
    Research Division, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, Massachusetts 02215, USA
    Nature 421:856-9. 2003
    Secretion of leptin from adipocytes communicates body energy status to the brain by activating the leptin receptor long form (LRb)...
  7. pmc Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals
    David Patsouris
    Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Cell Metab 8:301-9. 2008
    b>Obese adipose tissue is characterized by infiltration of macrophages. We and others recently showed that a specific subset of macrophages is recruited to obese adipose and muscle tissue...
  8. 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
    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...
  9. pmc Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes
    Kimihiko Matsusue
    Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Frederick, Maryland 20892, USA
    J Clin Invest 111:737-47. 2003
    To elucidate the function of PPARgamma in leptin-deficient mouse (ob/ob) liver, a PPARgamma liver-null mouse on an ob/ob background, ob/ob-PPARgamma(fl/fl)AlbCre(+), was produced using a floxed PPARgamma allele, PPARgamma(fl/fl), and Cre ..
  10. 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...
  11. pmc Hyperleptinemia is required for the development of leptin resistance
    Zachary A Knight
    Howard Hughes Medical Institute, Laboratory of Molecular Genetics, The Rockefeller University, New York, New York, United States of America
    PLoS ONE 5:e11376. 2010
    b>Leptin regulates body weight by signaling to the brain the availability of energy stored as fat. This negative feedback loop becomes disrupted in most obese individuals, resulting in a state known as leptin resistance...
  12. ncbi Leptin regulates proinflammatory immune responses
    S Loffreda
    Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA
    FASEB J 12:57-65. 1998
    ..Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity...
  13. pmc Inflammation and adipose tissue macrophages in lipodystrophic mice
    Laura Herrero
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:240-5. 2010
    ..Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance...
  14. 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
    ..It has been demonstrated that exogenous human OB protein (leptin) treatment reduces food intake and weight gain, as well as insulin, glucose, and corticosterone levels in ob/ob ..
  15. ncbi Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
    Yasuhiko Minokoshi
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Nature 415:339-43. 2002
    b>Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function...
  16. pmc Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight
    Hyun Kyong Kim
    Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea
    Diabetes 59:2772-80. 2010
    ..In the present study, we investigated the physiological role of Angptl4 in central regulation of body weight homeostasis...
  17. pmc The IRE1alpha-XBP1 pathway of the unfolded protein response is required for adipogenesis
    Haibo Sha
    Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
    Cell Metab 9:556-64. 2009
    ..Taken together, our data show that the IRE1alpha-XBP1 pathway plays a key role in adipocyte differentiation by acting as a critical regulator of the morphological and functional transformations during adipogenesis...
  18. pmc Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development
    Vicent Ribas
    David Geffen School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, University of California, Los Angeles, CA 90095 7073, USA
    Proc Natl Acad Sci U S A 108:16457-62. 2011
    ..A similar obese phenotype and increased atherosclerotic lesion area was displayed in LDL receptor-KO mice transplanted with ERα(-/..
  19. pmc Ablation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertility
    Qi Wu
    Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 109:3155-60. 2012
    b>Leptin-deficient (Lep(ob/ob)) mice are obese, diabetic, and infertile. Ablation of neurons that make agouti-related protein (AgRP) in moderately obese adult Lep(ob/ob) mice caused severe anorexia...
  20. ncbi Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
    J C Yoon
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 413:131-8. 2001
    ..These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver...
  21. ncbi The adipoinsular axis: effects of leptin on pancreatic beta-cells
    T J Kieffer
    Departments of Medicine and Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
    Am J Physiol Endocrinol Metab 278:E1-E14. 2000
    ..for the existence of an adipoinsular axis, a dual hormonal feedback loop involving the hormones insulin and leptin produced by pancreatic beta-cells and adipose tissue, respectively...
  22. ncbi Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing beta-oxidation in skeletal muscle
    Agnieszka Dobrzyn
    Dept of Biochemistry, Univ of Wisconsin, 433 Babcock Dr, Madison, WI 53706, USA
    Am J Physiol Endocrinol Metab 288:E599-607. 2005
    ..significantly increases insulin sensitivity in skeletal muscles and corrects the hypometabolic phenotype of leptin-deficient ob/ob mice, indicating the direct antilipotoxic action of SCD1 deficiency...
  23. ncbi 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
    Hui Gao
    Department of Biosciences and Nutrition, Karolinska Institutet, Novum, S 14157 Huddinge, Sweden
    Mol Endocrinol 20:1287-99. 2006
    ..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...
  24. pmc Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice
    Yaron Ilan
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:9765-70. 2010
    b>Leptin-deficient ob/ob mice are overweight, develop insulin resistance, and serve as a model for type 2 diabetes (T2D)...
  25. pmc Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice
    Michael M Scott
    Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9077, USA
    J Clin Invest 121:2413-21. 2011
    b>Leptin is an adipose-derived hormone that signals to inform the brain of nutrient status; loss of leptin signaling results in marked hyperphagia and obesity...
  26. ncbi A leptin missense mutation associated with hypogonadism and morbid obesity
    A Strobel
    Nat Genet 18:213-5. 1998
  27. 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...
  28. 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 ..
  29. 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
    ..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...
  30. pmc Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine- and amphetamine-regulated transcript neurons of the extended central amygdala
    Rebecca L Leshan
    Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Neurosci 30:5713-23. 2010
    b>Leptin acts via its receptor (LepRb) to regulate neural circuits in concert with body energy stores. In addition to acting on a number of hypothalamic structures, leptin modulates the mesolimbic dopamine (DA) system...
  31. pmc Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons
    Gwendolyn W Louis
    Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Neurosci 30:11278-87. 2010
    b>Leptin, the adipose-derived hormonal signal of body energy stores, acts via the leptin receptor (LepRb) on neurons in multiple brain regions...
  32. pmc The farnesoid X receptor regulates adipocyte differentiation and function by promoting peroxisome proliferator-activated receptor-gamma and interfering with the Wnt/beta-catenin pathways
    Mouaadh Abdelkarim
    Universite Lille Nord de France, F 59000 Lille, France
    J Biol Chem 285:36759-67. 2010
    ..Our results show that genetically obese FXR(-/-)/ob/ob mice displayed a resistance to rosiglitazone treatment...
  33. pmc Leptin induces phosphorylation of neuronal nitric oxide synthase in defined hypothalamic neurons
    Jose Donato
    Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Endocrinology 151:5415-27. 2010
    Studies have indicated that the neurotransmitter nitric oxide (NO) mediates leptin's effects in the neuroendocrine reproductive axis. However, the neurons involved in these effects and their regulation by leptin is still unknown...
  34. pmc Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons
    Jose Donato
    Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9077, USA
    J Clin Invest 121:355-68. 2011
    ..The adipocyte-derived hormone leptin is a key metabolic signal to the neuroendocrine reproductive axis...
  35. pmc Leptin action in pubertal development: recent advances and unanswered questions
    Carol F Elias
    Department of Internal Medicine, Division of Hypothalamic Research and Green Center for Reproductive Biology Sciences, University of Texas Southwestern UTSW Medical Center, Dallas, TX 75390, USA
    Trends Endocrinol Metab 23:9-15. 2012
    ..This review will focus on recent data unveiling the sites of leptin action in pubertal development that were generated using novel molecular techniques and genetically engineered ..
  36. pmc Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice
    Jennifer W Hill
    Division of Hypothalamic Research, Department of Internal Medicine and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 118:1796-805. 2008
    Normal food intake and body weight homeostasis require the direct action of leptin on hypothalamic proopiomelanocortin (POMC) neurons. It has been proposed that leptin action requires PI3K activity...
  37. pmc Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice
    Neira Sainz
    Metabolic Research Laboratory, University of Navarra, Pamplona, Spain
    PLoS ONE 4:e6808. 2009
    Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass...
  38. ncbi Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin
    Y Ogawa
    Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan
    Diabetes 48:1822-9. 1999
    ..b>Leptin is an adipocyte-derived satiety factor that plays an important role in the regulation of energy homeostasis, and ..
  39. 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
    ..Prevention of the fasting-induced fall in the level of the adipocyte-derived hormone leptin by administering exogenous recombinant leptin protected mice from these starvation-induced thymic changes...
  40. ncbi Genetically obese MMTV-TGF-alpha/Lep(ob)Lep(ob) female mice do not develop mammary tumors
    Margot P Cleary
    The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
    Breast Cancer Res Treat 77:205-15. 2003
    ..mice are not a good model to evaluate the effect of body weight on MT development possibly due to leptin deficiency...
  41. ncbi 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)
    Ruben R Gonzalez
    Boston Biomedical Research Institute, Watertown, Massachusetts 02472, USA
    J Biol Chem 281:26320-8. 2006
    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 ..
  42. pmc Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer
    Ruben Rene Gonzalez
    Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA
    Breast Cancer Res 11:R36. 2009
    We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and ..
  43. ncbi On raising energy expenditure in ob/ob mice
    J Himms-Hagen
    Science 276:1132-3. 1997
  44. 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
    ..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...
  45. 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
    The BTBR mouse strain harbors alleles promoting insulin resistance. When made genetically obese (ob/ob), these mice develop severe type 2 diabetes (fasting glucose >400 mg/dL)...
  46. ncbi Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes
    K Ebihara
    Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Diabetes 50:1440-8. 2001
    ..We have also produced transgenic "skinny" mice that have hepatic overexpression of leptin (LepTg/+) and no adipocyte triglyceride stores, and are hypophagic and show increased insulin sensitivity...
  47. ncbi Altered insulin signaling in retinal tissue in diabetic states
    Tatsuya Kondo
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 279:37997-8006. 2004
    ..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...
  48. doi 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
    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...
  49. pmc Endocrine regulation of energy metabolism by the skeleton
    Na Kyung Lee
    Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Cell 130:456-69. 2007
    ..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...
  50. 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
    ..In obese WT and ob/ob (leptin-deficient) mice, brief treatment with CD3-specific antibody or its F(ab')(2) fragment, reduces the predominance of ..
  51. ncbi Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice
    C Vaisse
    Laboratory of Metabolic Diseases, Rockefeller University, New York, New York 10021, USA
    Nat Genet 14:95-7. 1996
    b>Leptin, a hormone secreted by adipocytes, regulates the size of the adipose tissue mass through effects on satiety and energy metabolism. Leptin's precise sites of action are not known...
  52. ncbi The leptin receptor
    L A Tartaglia
    Millenium Pharmaceuticals, Cambridge, Massachusetts 02139, USA
    J Biol Chem 272:6093-6. 1997
  53. ncbi Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia
    Peter Mancuso
    Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA
    J Immunol 168:4018-24. 2002
    b>Leptin is an adipocyte-derived hormone that is secreted in correlation with total body lipid stores. Serum leptin levels are lowered by the loss of body fat mass that would accompany starvation and malnutrition...
  54. ncbi Reduced cholesterol accumulation by leptin deficient (ob/ob) mouse macrophages
    M Kjerrulf
    Dept of Molecular Pharmacology, AstraZeneca R and D, Molndal, Sweden
    Inflamm Res 55:300-9. 2006
    Although presenting many aspects of the metabolic syndrome, leptin deficient (ob/ob) mice do not spontaneously develop atherosclerosis...
  55. 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...
  56. pmc Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice
    Gregory J Morton
    Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, USA
    Am J Physiol Endocrinol Metab 300:E392-401. 2011
    ..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 ..
  57. 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
    ..To test this hypothesis, we studied leptin-deficient and leptin receptor-deficient mice that are obese and hypogonadic...
  58. ncbi Leptin regulates bone formation via the sympathetic nervous system
    Shu Takeda
    Department of Molecular and Human Genetics, One Baylor Plaza, Houston, TX 77030, USA
    Cell 111:305-17. 2002
    We previously showed that leptin inhibits bone formation by an undefined mechanism...
  59. doi Leptin prevents the metabolic effects of adiponectin in L6 myotubes
    X Fang
    Department of Biology, York University, Toronto, ON, Canada
    Diabetologia 52:2190-200. 2009
    Adiponectin and leptin are negatively and positively correlated with human obesity respectively, and have both been shown to regulate energy metabolism in skeletal muscle...
  60. pmc Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia
    P Sarraf
    Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Exp Med 185:171-5. 1997
    ..and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat...
  61. ncbi Effect of leptin deficiency on metabolic rate in ob/ob mice
    M J Breslow
    Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Am J Physiol 276:E443-9. 1999
    Reduced metabolic rate may contribute to weight gain in leptin-deficient (ob/ob) mice; however, available studies have been criticized for referencing O2 consumption (VO2) to estimated rather than true lean body mass...
  62. pmc Abnormal regulation of the leptin gene in the pathogenesis of obesity
    E Ioffe
    Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 95:11852-7. 1998
    A subset of obese humans has relatively low plasma levels of leptin. This finding has suggested that in some cases abnormal regulation of the leptin gene in adipose tissue is etiologic in the pathogenesis of the obese state...
  63. ncbi Development of intestinal inflammation in double IL-10- and leptin-deficient mice
    Britta Siegmund
    Charite Universitaetsmedizin Berlin, Campus Benjamin Franklin, Germany
    J Leukoc Biol 76:782-6. 2004
    b>Leptin-deficient (ob/ob) mice are resistant in different models of autoimmunity and inflammation, suggesting that leptin regulates immunity and inflammation...
  64. 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
    ..The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight...
  65. ncbi Genetic obesity unmasks nonlinear interactions between murine type 2 diabetes susceptibility loci
    J P Stoehr
    Department of Biochemistry, University of Wisconsin Madison, USA
    Diabetes 49:1946-54. 2000
    ..We hypothesized that the genetic determinants of the insulin resistance syndrome might also predispose genetically obese mice to severe diabetes...
  66. ncbi Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome
    Lydia E Kuo
    Department of Physiology and Biophysics, Georgetown University Medical Center, 3900 Reservoir Rd NW, BSB 234, Washington, DC 20057, USA
    Nat Med 13:803-11. 2007
    ..Thus, manipulations of NPY2R activity within fat tissue offer new ways to remodel fat and treat obesity and metabolic syndrome...
  67. ncbi Thermogenesis in diabetes-obesity syndromes in mutant mice
    D L Coleman
    Diabetologia 22:205-11. 1982
    The two mouse mutants, obese (ob) and diabetes (db), cause similar diabetes-obesity syndromes that are characterized by a marked increase in apparent metabolic efficiency with regard to utilization of energy...
  68. 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
    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...
  69. ncbi LPS-induced anorexia in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice
    R Faggioni
    Department of Medicine, University of California, USA
    Am J Physiol 273:R181-6. 1997
    Administration of endotoxin (lipopolysaccharide, LPS) induces profound anorexia. Injection of leptin decreases food intake in mice. Recently, we reported that LPS and cytokines increase leptin levels in hamsters...
  70. ncbi A leptin dose-response study in obese (ob/ob) and lean (+/?) mice
    R B Harris
    Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA
    Endocrinology 139:8-19. 1998
    This experiment determined the amount of leptin required to correct different abnormalities in leptin-deficient ob/ob mice...
  71. ncbi Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy
    I Shimomura
    Department of Molecular Genetics, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235 9046, USA
    Nature 401:73-6. 1999
    ..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...
  72. pmc Torpor in mice is induced by both leptin-dependent and -independent mechanisms
    O Gavrilova
    Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 96:14623-8. 1999
    We tested the effect of chronic leptin treatment on fasting-induced torpor in leptin-deficient A-ZIP/F-1 and ob/ob mice...
  73. pmc Acute leptin deficiency, leptin resistance, and the physiologic response to leptin withdrawal
    Jason M Montez
    Chromocell Corporation, 675 US Highway One, North Brunswick, NJ 08902 USA
    Proc Natl Acad Sci U S A 102:2537-42. 2005
    Food restriction and weight loss result in reduced plasma leptin, which is associated with a pleiotropic biologic response...
  74. ncbi Fat apoptosis through targeted activation of caspase 8: a new mouse model of inducible and reversible lipoatrophy
    Utpal B Pajvani
    Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Nat Med 11:797-803. 2005
    ..responsive to glucose-stimulated insulin secretion and show increased food intake independent of the effects of leptin. Most importantly, we show that functional adipocytes can be recovered upon cessation of treatment, allowing the ..
  75. ncbi Tomosyn is expressed in beta-cells and negatively regulates insulin exocytosis
    Wei Zhang
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Diabetes 55:574-81. 2006
    ..Hence, in the pancreatic beta-cell, tomosyn negatively regulates insulin exocytosis...
  76. pmc A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic beta-cells
    Ke Ning
    Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
    EMBO J 25:2377-87. 2006
    In obesity and diabetes, the ability of hypothalamic neurons to sense and transduce changes in leptin and insulin levels is compromised...
  77. ncbi Maintenance of adiponectin attenuates insulin resistance induced by dietary conjugated linoleic acid in mice
    Aparna Purushotham
    Department of Human Nutrition, Ohio State University, Columbus, OH 43210, USA
    J Lipid Res 48:444-52. 2007
    ..Our objective was to determine whether the maintenance of adipokines, mainly leptin and adiponectin, by either removing CLA from diets or using an adiponectin enhancer, rosiglitazone (ROSI), could ..
  78. ncbi Leptin-induced matrix metalloproteinase-2 secretion is suppressed by trans-10,cis-12 conjugated linoleic acid
    Hyun Seuk Moon
    School of Agricultural Biotechnology, Seoul National University, Seoul 151 921, Republic of Korea
    Biochem Biophys Res Commun 356:955-60. 2007
    It has long been recognized that leptin, a hormone made by adipocytes, is an important circulating signal for the regulation of body weight...
  79. ncbi Thermoregulation and non-shivering thermogenesis in the genetically obese (ob/ob) mouse
    P Trayhurn
    Pflugers Arch 373:189-93. 1978
    1. The capacity ofr thermoregulation and thermogenesis in lean and genetically obese (ob/ob) mice has been investigated. 2...
  80. ncbi Laboratory animals exhibiting obesity and diabetes syndromes
    L Herberg
    Metabolism 26:59-99. 1977
    ..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 ..
  81. ncbi Thermogenic defect in pre-obese ob/ob mice
    P Trayhurn
    Nature 266:60-2. 1977
  82. ncbi The influence of genetic background on the expression of the obese (Ob) gene in the mouse
    D L Coleman
    Diabetologia 9:287-93. 1973
  83. ncbi Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks
    L A Campfield
    Department of Metabolic Diseases, Hoffmann La Roche Incorporated, Nutley, NJ 07110, USA
    Science 269:546-9. 1995
    ..administration of microgram doses of OB protein reduced food intake and body weight of ob/ob and diet-induced obese mice but not in db/db obese mice...
  84. ncbi Positional cloning of the mouse obese gene and its human homologue
    Y Zhang
    Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021
    Nature 372:425-32. 1994
    The mechanisms that balance food intake and energy expenditure determine who will be obese and who will be lean. One of the molecules that regulates energy balance in the mouse is the obese (ob) gene...
  85. ncbi Genetic typing of the mouse ob mutation by PCR and restriction enzyme analysis
    T Hirasawa
    Center for Experimental Animals Development, Shionogi and Co, Ltd, Shiga, Japan
    Exp Anim 46:75-8. 1997
    A genetic typing method for the mouse obese (ob) mutation by PCR and restriction fragment length polymorphism (RFLP) analysis was developed. Three genotypes (ob/ob, ob/+ and +/+) of the ob mouse are rapidly differentiated with this assay...
  86. ncbi Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene
    D J Good
    Acquired Gene Rearrangement Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20889, USA
    Nat Genet 15:397-401. 1997
    ..Nhlh2 is expressed in the ventral-medial and lateral hypothalamus, Rathke's pouch and in the anterior lobe of the adult pituitary. Our results support a role for Nhlh2 in the onset of puberty and the regulation of body weight metabolism...
  87. ncbi Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress
    M L Heiman
    Endocrine Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46250, USA
    Endocrinology 138:3859-63. 1997
    b>Leptin is a newly identified protein hormone that is synthesized and secreted by adipose tissue. Absence of the mature hormone is responsible for the obese phenotype of ob/ob mice...
  88. pmc Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function
    R S Ahima
    Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 101:1020-7. 1998
    b>Leptin is thought to regulate energy balance through effects on food intake and thermogenesis...
  89. ncbi Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting
    D G Baskin
    Department of Veterans Affairs Puget Sound Health Care System, Department of Medicine, University of Washington, Seattle 98108, USA
    Diabetes 47:538-43. 1998
    The responsiveness of the hypothalamus to the inhibitory effects of leptin on food intake and body weight is influenced by multiple factors, including deficiency of either leptin or leptin receptors (Ob-R)...
  90. ncbi Induction of uncoupling protein expression in brown and white adipose tissue by leptin
    S P Commins
    Department of Medicine, Medical University of South Carolina, Charleston 29425, USA
    Endocrinology 140:292-300. 1999
    ..In ob/ob mice, the absence of leptin affects both components of the energy balance equation, and the mice become morbidly obese after weaning...
  91. 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
    b>Leptin controls feeding behavior and insulin secretion from pancreatic beta-cells. Insulin stimulates the production of leptin, thereby establishing an adipoinsular axis...
  92. ncbi Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting
    T M Mizuno
    Fishberg Center for Neurobiology, Department of Geriatrics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Endocrinology 140:814-7. 1999
    ..Y (NPY) messenger RNA (mRNA), AGRP mRNA is produced in the hypothalamic arcuate nucleus and is elevated in leptin-deficient ob/ob and leptin-resistant db/db mice...
  93. ncbi Altered expression of hepatic CYP2E1 and CYP4A in obese, diabetic ob/ob mice, and fa/fa Zucker rats
    A Enriquez
    Department of Medicine, University of Sydney, Westmead Hospital, New South Wales, Australia
    Biochem Biophys Res Commun 255:300-6. 1999
    ..obesity-related (type II) diabetes, we analyzed the hepatic expression of CYP2E1 and CYP4A in ob/ob mice which are leptin deficient, and fa/fa Zucker rats which have defective leptin receptor function...
  94. ncbi Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus
    I Shimomura
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9046, USA
    J Biol Chem 274:30028-32. 1999
    ..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 ..
  95. ncbi Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice
    A L Mark
    Specialized Center of Research in Hypertension Genetics and the Cardiovascular Center, Department of Internal Medicine, University of Iowa, Iowa City, USA
    J Hypertens 17:1949-53. 1999
    ..ob/ob(Lep(ob)/Lep(ob)) mice have a mutation in the ob gene and are leptin-deficient...
  96. ncbi Requirement for leptin in the induction and progression of autoimmune encephalomyelitis
    G Matarese
    Cattedra di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di Napoli Federico II, Napoli, Italy
    J Immunol 166:5909-16. 2001
    Recent evidence indicates that leptin modifies T cell immunity, and may provide a key link between nutritional deficiency and immune dysfunction...
  97. 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
    We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling...
  98. ncbi Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss
    Paul Cohen
    Laboratory of Molecular Genetics, Center for Studies in Physics and Biology, Rogosin Institute, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 297:240-3. 2002
    b>Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. To examine the mechanism underlying leptin's metabolic actions, we used transcription profiling to identify leptin-regulated genes in ob/ob liver...
  99. ncbi Gene expression profiles of nondiabetic and diabetic obese mice suggest a role of hepatic lipogenic capacity in diabetes susceptibility
    Hong Lan
    Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA
    Diabetes 52:688-700. 2003
    ..We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased...
  100. ncbi Rapid recruitment of inflammatory monocytes is independent of neutrophil migration
    Robert B Henderson
    Leukocyte Adhesion Laboratory, Cancer Research United Kingdom London Research Institute, Lincoln s Inn Fields Laboratories, London WC2A 3PX, UK
    Blood 102:328-35. 2003
    ..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...
  101. 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...

Research Grants43

  1. Transport of neurotrophic cytokines after spinal cord injury
    Weihong Pan; Fiscal Year: 2007
    ..Understanding the mechanisms of cytokine transport at this regulatory interface would help in the design of new approaches to treat SCI. ..
  2. Transport of TNFalpha across the BBB
    Weihong Pan; Fiscal Year: 2008
    ..These transporters could be novel drug targets and therefore provide promising therapeutic potential. [unreadable] [unreadable]..
  3. Conference on Obesity
    Michael Schwartz; Fiscal Year: 2003
    ..Energy homeostasis involves humoral signals such as leptin that create a circuit between peripheral tissues involved in energy storage and utilization and central networks ..
  4. HYPOTHALAMIC PEPTIDES, FOOD INTAKE, AND DIABETES
    Michael Schwartz; Fiscal Year: 2006
    ..neuronal systems in the arcuate nucleus (ARC) of the hypothalamus are regulated by hormones such as insulin and leptin that circulate in proportion to body fat mass has received strong support from studies using this model...
  5. TRH in mediating the bradycardia of caloric restriction
    Steven Swoap; Fiscal Year: 2005
    ..attention being paid to the cardiovascular disease risk linked to the tachycardia that is commonly seen in obese patients...
  6. Integration of Long- and Short-Term Control of Feeding
    Michael Schwartz; Fiscal Year: 2004
    ..Following the cloning of the ob gene, this model was expanded to include the adipocyte hormone, leptin. It has subsequently become evident that many of leptin's CNS effects overlap with those induced by insulin, and ..
  7. Mentored Clinical Research Scholar Program at Iowa
    ALLYN MARK; Fiscal Year: 2007
    ..These and other University research programs extend into the community--statewide and beyond--and include numerous disease registers and a broad network of collaborating institutions. [unreadable] [unreadable] [unreadable]..
  8. ApoB-Proteoglycan Interaction and Atherosclerosis
    Zhouji Chen; Fiscal Year: 2006
    ..Such information will advance our understanding of mechanisms of atherosclerosis and, in turn, facilitate developing new therapeutic strategies to treat atherosclerotic diseases. [unreadable] [unreadable]..
  9. Effect of Leptin on Trophoblast Invasiveness
    Laura Schulz; Fiscal Year: 2006
    I propose to investigate the relationship between leptin and trophobiast invasion...
  10. Role of Leucine Metabolism in Leucine Signaling
    CHRISTOPHER JOHN LYNCH; Fiscal Year: 2010
    ..The implication of our ongoing research is that blocking the first step in BCAA metabolism with a drug, or to a less extent increasing dietary BCAAs, will promote weight loss. ..
  11. Opiate Addiction and HIV-1 Induced Release of Cytokines
    William Banks; Fiscal Year: 2006
    ....
  12. ENERGY HOMEOSTASIS IN HUMAN OBESITY
    Rudolph Leibel; Fiscal Year: 2001
    One third of the U.S. population over the age of 20 (58 million individuals) is obese. The prevalence of obesity in children is approximately 20% and rates of obesity are disproportionately high among Black and Hispanic women...
  13. Regulation of Pulmonary Host Defense by Leptin
    Peter Mancuso; Fiscal Year: 2010
    ..b>Leptin is hormone produced by adipose tissue that is reduced in the energy malnourished and is known to regulate innate ..
  14. A model of obesity-associated severe acute pancreatitis
    Giamila Fantuzzi; Fiscal Year: 2007
    ..of AP patients - for 3 to 5 days induces mild pancreatic damage in non-obese wild type mice, but very severe AP in leptin-deficient, massively obese ob/ob mice...
  15. MOLECULAR DETERMINANTS OF LEPTIN RECEPTOR/JAK2 SIGNALING
    Martin Myers; Fiscal Year: 2007
    This application, entitled, "Molecular Determinants of Leptin Receptor/Jak2 Signaling," is a revised competitive renewal of DK56731...
  16. Matrix Metalloproteinases, Exercise, and Muscle Damage
    David Allen; Fiscal Year: 2008
    ..Finally, subjects will be genotyped for known functional MMP promoter polymorphisms, which will be correlated with MMP levels and muscle damage and soreness following eccentric exercise. ..
  17. REGULATION OF ADIPOCYTE PROTEIN SYNTHESIS BY AMINO ACIDS
    Christopher Lynch; Fiscal Year: 2007
    ..it regulates have critical roles in translational regulation of protein synthesis, adipocyte differentiation, leptin, de novo lipogenesis, cell cycle progression, hypertrophic growth of post-mitotic tissues and tissue morphogenesis...
  18. Role of Leptin in murine modeles of IBD
    Giamila Fantuzzi; Fiscal Year: 2007
    The goal of this project is to investigate the mechanisms by which leptin deficiency regulates susceptibility to intestinal inflammation in mice...
  19. Prevention of skin cancer by green tea polyphenols
    Santosh Katiyar; Fiscal Year: 2009
    ..Importantly, worldwide interest in green tea as a cancer chemopreventive agent for humans is increasing because it is non-toxic, affordable, popular beverage and is effective in a wide range of organs. ..
  20. Intermittent food restriction prevents mammary tumors
    MARGOT CLEARY; Fiscal Year: 2008
    ..1- The protective effect of intermittent restriction/refeeding is mediated by decreased serum IGF-I and leptin and effects on signaling pathways and/or proliferation/apoptosis; 2-The protective effect of intermittent ..
  21. Prion Transport Across the Blood-Brain Barrier
    William Banks; Fiscal Year: 2009
    ..To cause disease, prions must cross the blood-brain barrier to enter the brain. We will determine how prions cross the BBB. Knowing how prions enter the brain should lead to strategies on how to prevent prion diseases. ..
  22. Role of Acetaldehyde in Alcoholic Cardiomyopathy
    Jun Ren; Fiscal Year: 2008
    ..Our long-term goal is to establish the toxic mechanism of acetaldehyde in the development of alcoholic cardiomyopathy so that prevention and treatment can be optimized [unreadable] [unreadable]..
  23. Leptin Signaling in Cardiac Hypertrophy
    LILI BAROUCH; Fiscal Year: 2008
    ..b>Leptin, the ob gene product, is a hormone that regulates energy balance and adipose stores while also exerting ..
  24. ANGIOTENSIN AND CENTRAL NEUROHUMORAL ACTIVATION IN CHF
    Robert Felder; Fiscal Year: 2005
    ..This work will provide new information concerning the role of the central nervous system in the pathophysiology of CHF and will draw attention to the possibility of CNS directed drug therapy for heart failure. ..
  25. Prevention of Photocarcinogenesis by antioxidant
    Santosh Katiyar; Fiscal Year: 2003
    ..abstract_text> ..
  26. Role of glucocorticoids in hypoglycemia unawareness
    Lauren Jacobson; Fiscal Year: 2003
    ..abstract_text> ..
  27. IGF-1, Oxidative Stress and Cardiovascular Aging
    Jun Ren; Fiscal Year: 2002
    ..Our long-term goal is to establish the causal link among IGF-1 deficiency, enhanced oxidative damage and ventricular dysfunction in the progression of cardiovascular aging so that hormonal or antioxidant therapy can be optimized...
  28. CNS Counterregulatory Mechanisms
    Lauren Jacobson; Fiscal Year: 2004
    ..These studies will provide novel information on the neuropharmacology of glucose control that may reveal therapeutic strategies to prevent hypoglycemia unawareness. ..
  29. PTS1 Regulation of Brain Met Enk Levels in Alcoholism
    William Banks; Fiscal Year: 2004
    ..abstract_text> ..
  30. Determinants of Tolerance to Nitrous Oxide Hypothermia
    Karl Kaiyala; Fiscal Year: 2004
    ..These studies have theoretical importance for understanding the mechanisms of drug tolerance and will begin to suggest the physiological basis of individual differences in vulnerability to addiction and drug abuse. ..
  31. Mechanisms of HIV Transport Across the BBB
    William Banks; Fiscal Year: 2004
    ....
  32. Prevention of UV-carcinogenesis by antioxidant
    Santosh Katiyar; Fiscal Year: 2004
    ..abstract_text> ..
  33. Sleep Disordered Breathing and Glucose Regulation
    Vsevolod Polotsky; Fiscal Year: 2006
    ..Furthermore, the absence of the metabolic hormone leptin resulted in a more pronounced hyperglycemic phase in response to IH compared to wildtype mice...
  34. Conference on Obesity
    Rudolph Leibel; Fiscal Year: 2004
    ....
  35. UCP2 in the pathogenesis of steatohepatitis
    GYORGY BAFFY; Fiscal Year: 2005
    ..Knowledge of the biochemical actions and genetic regulation of UCP2 in the liver will advance our understanding about the role of UCP2 and the pathophysiology of SH. ..
  36. ODORANT-RECEPTOR INTERACTIONS IN OLFACTORY NEURONS
    Thomas Getchell; Fiscal Year: 2005
    ..Understanding the signaling regulating neurogenesis in the OE will yield insights into mechanisms for restoring olfactory function compromised by aging, trauma, and neurodegenerative diseases. ..
  37. In Vivo Kinetic Biomarkers of Hepatic Toxicity
    Scott Turner; Fiscal Year: 2005
    ..This work will provide a solid foundation for regulatory approval of our toxicity screen, for extension of our work to other end organs, and for use in humans. ..
  38. Kinetic Biomarkers of Joint Space Molecules in OA
    Scott Turner; Fiscal Year: 2005
    ..These tools may allow significant advances in our basic understanding of the biology of the extracellular matrix in the joint space, with potential application to the prevention and treatment of arthritic disorders. ..
  39. Proanthocyanidins: Novel Skin Cancer Preventive Agent
    Santosh Katiyar; Fiscal Year: 2006
    ..Prevention of skin cancer risk will result to protect and prolong the human health and lives. ..
  40. PHOSPHOINOSITIDE HYDROLYSIS AND BETA CELL SECRETION
    Walter Zawalich; Fiscal Year: 2006
    ..These aims will be accomplished by using sound principles of experimentation and employing isolated islets that retain their in vivo sensitivity to glucose. ..
  41. Neuroadaptive Substrates for Nitrous Oxide Tolerance
    Karl Kaiyala; Fiscal Year: 2006
    ..This work will be the first to identify brain areas activated by a drug-induced hypothermic stimulus and its adaptive consequences. These studies have theoretical importance for understanding and treating drug addiction. ..
  42. Effects of Myostatin Deficiency on Bone Strength
    Mark Hamrick; Fiscal Year: 2007
    ..abstract_text> ..