Although low serum testosterone (T) is associated with metabolic disorders, the mechanism of this association is unclear. The objective of the present study was to investigate the combined effects of T deficiency and a high-fat diet (HFD) on hepatic lipid homeostasis in mice.
Orchiectomized (ORX) mice and sham-operated (SHAM) mice were randomly divided into five groups: SHAM mice fed a standard diet (SD), SHAM mice fed HFD, ORX mice fed SD, ORX mice fed HFD, and ORX mice fed HFD with T supplementation. After 4 weeks of treatment, we investigated the synthesis and secretion of lipids in the liver and detailed serum lipoprotein profiles in each group.
ORX mice fed HFD showed increased hepatic steatosis, markedly decreased serum triglyceride (TG) and TG-VLDL content, and increased serum very small-LDL content. Gene expression analysis revealed that ORX mice fed HFD showed significantly decreased expression of microsomal triglyceride transfer protein, lipin-1, peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ coactivator 1-α, and significantly increased sterol regulatory element-binding protein-1, diacylglycerol acyltransferase-2 and fatty acid synthase. Reduction of hepatic AMPK phosphorylation was observed in ORX mice fed HFD. These perturbations in ORX mice fed HFD were normalized to the levels of SHAM mice fed HFD by T supplementation.
T deficiency is associated with failure of lipid homeostasis mediated by altered expression of genes involved in hepatic assembly and secretion of lipids.
Abbreviations:T (testosterone), AR (androgen receptor), HFD (high-fat diet), SD (standard diet), ORX (orchiectomized), SHAM (sham-operated), PPAR (peroxisome proliferator-activated receptor), SREBP-1 (sterol regulatory element-binding protein 1), DGAT-2 (diacylglycerol acyltransferase 2), FAS (fatty acid synthase), MTP (microsomal transfer protein), Arf-1 (ADP-ribosylation factor-1), PGC-1α (PPAR-γ coactivator 1-α), HPLC (high-performance liquid chromatography), RT-PCR (reverse transcription-polymerase chain reaction)
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Published online: January 18, 2013
Accepted: December 10, 2012
Received: September 29, 2012
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.