Hyperleptinemia without obesity in male mice lacking androgen receptor in adipose tissue.
Insulin resistance occurs through an inadequate response to insulin by insulin target organs such as liver, muscle, and adipose tissue with consequent insufficient glucose uptake. In previous studies we demonstrated that whole body androgen receptor (AR) knockout (AR(-/y)) mice develop obesity and exhibit insulin and leptin resistance at advanced age. By examining adipose tissue-specific AR knockout (A-AR(-/y)) mice, we found A-AR(-/y) mice were hyperleptinemic but showed no leptin resistance, although body weight and adiposity index of A-AR(-/y) mice were identical with those of male wild-type control mice. Hypotriglyceridemia and hypocholesterolemia found in nonobese A-AR(-/y) mice suggested a beneficial effect of high leptin levels independent of fat deposition. Further examination showed that androgen-AR signaling in adipose tissue plays a direct regulatory role in leptin expression via enhanced estrogen receptor transactivation activity due to elevated intraadipose estrogens. The present study in A-AR(-/y) mice suggests a differential tissue-specific role of AR in energy balance control in males.
Yu
I-Chen
IC
Department of Pathology, George Whipple Laboratory for Cancer Research, and the Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA.
Lin
Hung-Yun
HY
Liu
Ning-Chun
NC
Wang
Ruey-Shen
RS
Sparks
Janet D
JD
Yeh
Shuyuan
S
Chang
Chawnshang
C
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D050218:Body Fat Distribution; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004734:Energy Metabolism / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D020738:Leptin / Q000097:blood* / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D010084:Oxidation-Reduction; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
D020738:Leptin; D008055:Lipids; D011944:Receptors, Androgen; C045073:Cre recombinase; D019426:Integrases