Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein.

Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 +/- 11.9 years [mean +/- SD]) than in 137 women (53.2 +/- 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.

[1]  P. de Mazancourt,et al.  Androgen regulation and site specificity of angiotensinogen gene expression and secretion in rat adipocytes. , 2000, American journal of physiology. Endocrinology and metabolism.

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

[3]  H. Azuma,et al.  Molecular pathogenesis of type I congenital plasminogen deficiency: expression of recombinant human mutant plasminogens in mammalian cells. , 1997, Blood.

[4]  T. Funahashi,et al.  Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. , 2001, Diabetes.

[5]  T Nakamura,et al.  Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. , 1999, Circulation.

[6]  C. Kahn,et al.  Insulin signalling and the regulation of glucose and lipid metabolism , 2001, Nature.

[7]  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.

[8]  C S Song,et al.  Regulation of androgen action. , 1999, Vitamins and hormones.

[9]  S. Kihara,et al.  Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages , 2001, Circulation.

[10]  N. Avdalović,et al.  The influence of testosterone on the synthesis and degradation rate of various RNA species in the mouse kidney. , 1975, Biochimica et biophysica acta.

[11]  R. Burcelin,et al.  Acute stimulation of glucose metabolism in mice by leptin treatment , 1997, Nature.

[12]  B. Çakır,et al.  Insulin Resistance in Nonobese Patients with Polycystic Ovary Syndrome , 2001, Hormone Research in Paediatrics.

[13]  V. Schreiber,et al.  Effect of alloxan diabetes on kidney growth in intact and castrated mice. , 1982, Acta endocrinologica.

[14]  T Nakamura,et al.  Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[15]  Philipp E. Scherer,et al.  The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor , 1998, Current Biology.

[16]  M. Saad,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Sexual Dimorphism in Plasma Leptin Concentration* , 2022 .

[17]  P. Björntorp,et al.  Mechanisms Behind Insulin Resistance in Rat Skeletal Muscle After Oophorectomy and Additional Testosterone Treatment , 1996, Diabetes.

[18]  H. Iwatsuka,et al.  Determination of Overall Insulin Sensitivity in Diabetic Mice, KK , 1982, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[19]  T. Funahashi,et al.  cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). , 1996, Biochemical and biophysical research communications.

[20]  S. Yamashita,et al.  Enhanced expression of PAI–1 in visceral fat: Possible contributor to vascular disease in obeisty , 1996, Nature Medicine.

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

[22]  S. Kihara,et al.  Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. , 2002, Journal of the American Society of Nephrology : JASN.

[23]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[24]  R. Hammer,et al.  Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy , 1999, Nature.

[25]  S. Kihara,et al.  Adiponectin, an Adipocyte-Derived Plasma Protein, Inhibits Endothelial NF-&kgr;B Signaling Through a cAMP-Dependent Pathway , 2000, Circulation.

[26]  T Nakamura,et al.  Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. , 1999, Biochemical and biophysical research communications.

[27]  Philipp E. Scherer,et al.  A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes (*) , 1995, The Journal of Biological Chemistry.

[28]  B. Spiegelman,et al.  Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. , 1995, The Journal of clinical investigation.

[29]  B. Spiegelman,et al.  Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. , 1993, Science.

[30]  R. Leibel,et al.  Effects of gender, body composition, and menopause on plasma concentrations of leptin. , 1996, The Journal of clinical endocrinology and metabolism.

[31]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[32]  B. Spiegelman,et al.  Adipogenesis and Obesity: Rounding Out the Big Picture , 1996, Cell.

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

[34]  M. Muraguchi,et al.  Gender-related difference in relationship between insulin resistance and serum leptin level in Japanese type 2 diabetic and non-diabetic subjects. , 2000, Endocrine journal.

[35]  R. Lobo,et al.  The influence of androgens on insulin resistance. , 1984, Fertility and sterility.

[36]  M. Matsuda,et al.  PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. , 2001, Diabetes.

[37]  NoriyukiOuchi,et al.  Adiponectin, an Adipocyte-Derived Plasma Protein, Inhibits Endothelial NF-&kgr;B Signaling Through a cAMP-Dependent Pathway , 2000, Circulation.

[38]  B. Spiegelman,et al.  AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity (*) , 1996, The Journal of Biological Chemistry.

[39]  B. Lowell,et al.  Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. , 1995, The Journal of clinical investigation.

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

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

[42]  NoriyukiOuchi,et al.  Novel Modulator for Endothelial Adhesion Molecules , 1999 .

[43]  T. Funahashi,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resistance , 2022 .