Neuroendocrine and metabolic effects of adipocyte-derived hormones.

Obesity is characterized by an increase in adipose tissue mass. Contrary to the previous view of adipose tissue as simply an inert tissue devoted to energy storage, studies over the past decade have shown that adipose tissue is actively involved in regulating physiological processes and participates in disease. Adipose tissue secretes factors that exert local and systemic effects. Leptin, pro-inflammatory cytokines, resistin and proteins involved in haemodynamic regulation and coagulation are increased in obesity while adiponectin is reduced. The production of active corticosteroids is also increased in obesity. There is now growing evidence that adipocyte secretory factors regulate energy homoeostasis, as well as cardiovascular and immune systems. Some adipocyte hormones, most notably leptin, act in the brain to influence the neuroendocrine axis and energy balance, whereas adiponectin and resistin exert opposing effects on glucose and lipids. Understanding the actions of adipocyte hormones will provide novel insights into the pathophysiology and treatment of obesity.

[1]  M. G. Myers,et al.  Leptin receptor signaling and the regulation of mammalian physiology , 2008, International Journal of Obesity.

[2]  R. Doherty Obesity-related insulin resistance is reversible after weight loss , 2006, Nature Clinical Practice Endocrinology &Metabolism.

[3]  Anil Kumar Singh,et al.  Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. , 2005, Biochemical and biophysical research communications.

[4]  C. Kusminski,et al.  Role of resistin in obesity, insulin resistance and Type II diabetes. , 2005, Clinical science.

[5]  M. Matsuda,et al.  Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. , 2005, Science.

[6]  P. Stewart,et al.  11β-Hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action , 2005 .

[7]  Eijiro Watanabe,et al.  Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Nimesh Mody,et al.  Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes , 2005, Nature.

[9]  Reiko Ohmori,et al.  Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease. , 2005, Journal of the American College of Cardiology.

[10]  P. Gorden,et al.  Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. , 2005, Diabetes.

[11]  John A Matochik,et al.  Effect of leptin replacement on brain structure in genetically leptin-deficient adults. , 2005, The Journal of clinical endocrinology and metabolism.

[12]  T. Kadowaki,et al.  Adiponectin and adiponectin receptors. , 2005, Endocrine reviews.

[13]  W. Boon,et al.  Estrogen--the good, the bad, and the unexpected. , 2005, Endocrine reviews.

[14]  G. Barsh,et al.  PI3K integrates the action of insulin and leptin on hypothalamic neurons. , 2005, The Journal of clinical investigation.

[15]  P. Scherer,et al.  Adiponectin: a relevant player in PPARγ-agonist-mediated improvements in hepatic insulin sensitivity? , 2005, International Journal of Obesity.

[16]  Anand Rohatgi,et al.  Resistin Is an Inflammatory Marker of Atherosclerosis in Humans , 2005, Circulation.

[17]  M. Birnbaum,et al.  Activation of SOCS-3 by Resistin , 2005, Molecular and Cellular Biology.

[18]  P. Gorden,et al.  The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients. , 2005, Metabolism: clinical and experimental.

[19]  H. Lodish,et al.  Visfatin: A New Adipokine , 2005, Science.

[20]  J. Seckl 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. , 2004, Current opinion in pharmacology.

[21]  T. Hudson,et al.  Human resistin gene polymorphism is associated with visceral obesity and fasting and oral glucose stimulated C-peptide in the Québec Family Study , 2004, Journal of endocrinological investigation.

[22]  A. Volpe,et al.  Recombinant human leptin in women with hypothalamic amenorrhea. , 2004, The New England journal of medicine.

[23]  S. Grinspoon,et al.  Endocrine and metabolic effects of physiologic r-metHuLeptin administration during acute caloric deprivation in normal-weight women. , 2004, The Journal of clinical endocrinology and metabolism.

[24]  M. Reilly,et al.  An Inflammatory Cascade Leading to Hyperresistinemia in Humans , 2004, PLoS medicine.

[25]  J. Yanovski,et al.  Effects of exogenous leptin on satiety and satiation in patients with lipodystrophy and leptin insufficiency. , 2004, The Journal of clinical endocrinology and metabolism.

[26]  I. S. Wood,et al.  Adipokines: inflammation and the pleiotropic role of white adipose tissue , 2004, British Journal of Nutrition.

[27]  H. Münzberg,et al.  N-acetylation of hypothalamic α-melanocyte-stimulating hormone and regulation by leptin , 2004 .

[28]  T. Saruta,et al.  Novel resistin promoter polymorphisms: association with serum resistin level in Japanese obese individuals. , 2004, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[29]  M. Lazar,et al.  Abnormal glucose homeostasis due to chronic hyperresistinemia. , 2004, Diabetes.

[30]  J. Olefsky,et al.  Adenovirus-mediated chronic "hyper-resistinemia" leads to in vivo insulin resistance in normal rats. , 2004, The Journal of clinical investigation.

[31]  B. Monia,et al.  Role of resistin in diet-induced hepatic insulin resistance. , 2004, The Journal of clinical investigation.

[32]  R. Ahima,et al.  Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. , 2004, Diabetes.

[33]  J. Flier,et al.  Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3 , 2004, Nature Medicine.

[34]  A. Yoshimura,et al.  Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity , 2004, Nature Medicine.

[35]  B. Lowell,et al.  Leptin Receptor Signaling in POMC Neurons Is Required for Normal Body Weight Homeostasis , 2004, Neuron.

[36]  Wadih Arap,et al.  Reversal of obesity by targeted ablation of adipose tissue , 2004, Nature Medicine.

[37]  R. Ahima,et al.  ERRATUM: Adiponectin acts in the brain to decrease body weight , 2004, Nature Network Boston.

[38]  Philipp E. Scherer,et al.  Disulfide-Dependent Multimeric Assembly of Resistin Family Hormones , 2004, Science.

[39]  H. Sul,et al.  Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[40]  R. Ahima,et al.  Adiponectin acts in the brain to decrease body weight , 2004, Nature Medicine.

[41]  S. Bouret,et al.  Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding , 2004, Science.

[42]  A. G. Roseberry,et al.  Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin , 2004, Science.

[43]  J. Flier,et al.  Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice. , 2004, Diabetes.

[44]  T. Horvath,et al.  Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[45]  R. L. Richardson,et al.  Adipose tissue angiogenesis. , 2004, Journal of animal science.

[46]  M. Lazar,et al.  Regulation of Fasted Blood Glucose by Resistin , 2004, Science.

[47]  J. Flier Obesity Wars Molecular Progress Confronts an Expanding Epidemic , 2004, Cell.

[48]  H. Münzberg,et al.  N-acetylation of hypothalamic alpha-melanocyte-stimulating hormone and regulation by leptin. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[49]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[50]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[51]  Stephen A. Smith,et al.  Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. , 2003, The Journal of clinical endocrinology and metabolism.

[52]  S. Zolotukhin,et al.  Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[53]  J. Flier,et al.  Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. , 2003, The Journal of clinical investigation.

[54]  W. Banks,et al.  Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. , 2003, American journal of physiology. Endocrinology and metabolism.

[55]  Philippe Froguel,et al.  Cloning of adiponectin receptors that mediate antidiabetic metabolic effects , 2003, Nature.

[56]  J. Chan,et al.  The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. , 2003, The Journal of clinical investigation.

[57]  Alexander S. Banks,et al.  STAT3 signalling is required for leptin regulation of energy balance but not reproduction , 2003, Nature.

[58]  T. Saibara,et al.  Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency. , 2003, The Journal of endocrinology.

[59]  G. Barsh,et al.  Is the energy homeostasis system inherently biased toward weight gain? , 2003, Diabetes.

[60]  H. Lodish,et al.  Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl–CoA carboxylase inhibition and AMP-activated protein kinase activation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[61]  O. Pedersen,et al.  Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism. , 2002, The Journal of clinical endocrinology and metabolism.

[62]  M. Stumvoll,et al.  Resistin and adiponectin--of mice and men. , 2002, Obesity research.

[63]  A. Meseguer,et al.  Sex steroid biosynthesis in white adipose tissue. , 2002, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[64]  P. Dupont,et al.  Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. , 2002, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[65]  B. Lowell,et al.  Adipose tissue mass can be regulated through the vasculature , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[66]  M. Matsuda,et al.  Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 , 2002, Nature Medicine.

[67]  Young-Bum Kim,et al.  PTP1B regulates leptin signal transduction in vivo. , 2002, Developmental cell.

[68]  P. Scherer,et al.  ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism , 2002, Trends in Endocrinology & Metabolism.

[69]  J. Flier,et al.  A Transgenic Model of Visceral Obesity and the Metabolic Syndrome , 2001, Science.

[70]  S. Yao,et al.  Aromatase-deficient (ArKO) mice accumulate excess adipose tissue , 2001, The Journal of Steroid Biochemistry and Molecular Biology.

[71]  John J. Mullins,et al.  Improved Lipid and Lipoprotein Profile, Hepatic Insulin Sensitivity, and Glucose Tolerance in 11β-Hydroxysteroid Dehydrogenase Type 1 Null Mice* , 2001, The Journal of Biological Chemistry.

[72]  S. O’Rahilly,et al.  Metabolism: Partial leptin deficiency and human adiposity , 2001, Nature.

[73]  J. Friedman,et al.  Selective deletion of leptin receptor in neurons leads to obesity. , 2001, The Journal of clinical investigation.

[74]  S. O’Rahilly,et al.  Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. , 2001, Diabetes.

[75]  Y. Terauchi,et al.  The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity , 2001, Nature Medicine.

[76]  P. Scherer,et al.  The adipocyte-secreted protein Acrp30 enhances hepatic insulin action , 2001, Nature Medicine.

[77]  H. Sul,et al.  A Cysteine-rich Adipose Tissue-specific Secretory Factor Inhibits Adipocyte Differentiation* , 2001, The Journal of Biological Chemistry.

[78]  J. Flier,et al.  Divergent Roles of SHP-2 in ERK Activation by Leptin Receptors* , 2001, The Journal of Biological Chemistry.

[79]  H. Lodish,et al.  Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[80]  M. Lazar,et al.  The hormone resistin links obesity to diabetes , 2001, Nature.

[81]  M. Lazar,et al.  A family of tissue-specific resistin-like molecules. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[82]  A. Thorburn,et al.  Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[83]  Clifford B. Saper,et al.  Leptin Regulation of Neuroendocrine Systems , 2000, Frontiers in Neuroendocrinology.

[84]  R. Ahima Leptin and the neuroendocrinology of fasting. , 2000, Frontiers of hormone research.

[85]  J Licinio,et al.  Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defe , 1999, The Journal of clinical endocrinology and metabolism.

[86]  A. Prentice,et al.  Effects of recombinant leptin therapy in a child with congenital leptin deficiency. , 1999, The New England journal of medicine.

[87]  J. Flier,et al.  Regulation of neuronal and glial proteins by leptin: implications for brain development. , 1999, Endocrinology.

[88]  S. Moestrup,et al.  Evidence for an essential role of megalin in transepithelial transport of retinol. , 1999, Journal of the American Society of Nephrology : JASN.

[89]  J. Flier,et al.  Distinct Physiologic and Neuronal Responses to Decreased Leptin and Mild Hyperleptinemia , 1999 .

[90]  C. Mantzoros,et al.  Sex differences in circulating human leptin pulse amplitude: clinical implications. , 1998, The Journal of clinical endocrinology and metabolism.

[91]  J. Halaas,et al.  Leptin and the regulation of body weight in mammals , 1998, Nature.

[92]  K. Clément,et al.  A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction , 1998, Nature.

[93]  J. Flier,et al.  Divergent Signaling Capacities of the Long and Short Isoforms of the Leptin Receptor* , 1997, The Journal of Biological Chemistry.

[94]  R. Sen Aris,et al.  Leptin Inhibits in Vitro Hypothalamic Somatostatin Secretion and Somatostatin mRNA Levels. , 1997, Endocrinology.

[95]  J. Flier,et al.  Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. , 1997, Endocrinology.

[96]  C. Mantzoros,et al.  Human leptin levels are pulsatile and inversely related to pituitary–ardenal function , 1997, Nature Medicine.

[97]  L. Tartaglia,et al.  The Leptin Receptor* , 1997, The Journal of Biological Chemistry.

[98]  J. Flier,et al.  Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. , 1997, Endocrinology.

[99]  C. Mantzoros,et al.  Role of leptin in the neuroendocrine response to fasting , 1996, Nature.

[100]  F. Chehab,et al.  Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin , 1996, Nature Genetics.

[101]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[102]  K. Hummel,et al.  Effects of parabiosis of normal with genetically diabetic mice. , 1969, The American journal of physiology.

[103]  G. C. Kennedy,et al.  The role of depot fat in the hypothalamic control of food intake in the rat , 1953, Proceedings of the Royal Society of London. Series B - Biological Sciences.

[104]  M. Dickie,et al.  Obese, a new mutation in the house mouse. , 1950, The Journal of heredity.