Session: SAT 338-357-Steroid Hormone Actions
Poster Board SAT-346
Tfm mice were fed a high-cholesterol diet ad libitum for 28 weeks and received either physiological TRT or placebo and were compared to wild-type littermates. Liver, muscle, visceral adipose and subcutaneous adipose tissue mRNA and protein were analysed by qPCR and western blotting for LXR expression and downstream targets involved in lipid metabolism (Acetyl coA carboxylase, ACC; Fatty acid synthase, FAS; Lipoprotein lipase, LPL; Apolipoprotein E, ApoE; ATP-binding cassette transporters, ABC-A1, ABC-G5; Stearoyl-CoA desaturase-1, SCD1), glucose control (Glucose transporter4, GLUT4; Hexokinases, HK2, HK4; Phosphofructokinase, PFK) and master regulators of lipid and glucose metabolism (peroxisome proliferator-activated receptors, PPARα; PPARγ; Sterol regulatory element-binding proteins, Srebp-1; Srepb-2).
LXR was down-regulated in liver and subcutaneous adipose of Tfm mice compared to wild-type with TRT increasing LXR expression. LXR was not altered in muscle or visceral adipose. Downstream targets of LXR were altered in the liver (↑FAS, ↑ACC, ↓ApoE, ↓ABC-A1, ↓HK4, ↓PFK) muscle (↓HK2, ↓GLUT4, ↓PFK) and subcutaneous adipose (↓LPL, ↓ABC-A1, ↓ApoE, ↓HK2, ↓GLUT4, ↓Srebp-1, ↓Srebp-2) of Tfm mice. All other targets in alternate tissues were not affected. TRT in Tfm mice returned hepatic FAS, ACC, ApoE, ABC-A1, HK4; muscle GLUT4 and subcutaneous ApoE, HK2, Srebp-1, Srebp-2 to wild-type levels suggesting both AR-independent and dependent mechanisms.
Testosterone may act through LXR to influence carbohydrate and lipid metabolism as a mechanism to improve insulin resistance which is, in part, independent of the AR.
Disclosure: THJ: Researcher, Bayer Healthcare, Consultant, Bayer Healthcare, Speaker, Bayer Healthcare, Consultant, Eli Lilly & Company, Consultant, Pro Strakan, Researcher, Pro Strakan, Speaker, Pro Strakan, Consultant, Merck, Consultant, Clarus. Nothing to Disclose: DMK, SA, VM, JB, DM, KSC
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