title: Testosterone deficiency induces markedly decreased serum triglycerides, increased small dense LDL, and hepatic steatosis mediated by dysregulation of lipid assembly and secretion in mice fed a high-fat diet.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 4weeks of treatment, we investigated the synthesis and secretion of lipids in the liver and detailed serum lipoprotein profiles in each group.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  T deficiency is associated with failure of lipid homeostasis mediated by altered expression of genes involved in hepatic assembly and secretion of lipids.
authors: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Takafumi
authors: T
authors: Senmaru
authors: Michiaki
authors: M
authors: Fukui
authors: Hiroshi
authors: H
authors: Okada
authors: Yusuke
authors: Y
authors: Mineoka
authors: Masahiro
authors: M
authors: Yamazaki
authors: Muneo
authors: M
authors: Tsujikawa
authors: Goji
authors: G
authors: Hasegawa
authors: Jo
authors: J
authors: Kitawaki
authors: Hiroshi
authors: H
authors: Obayashi
authors: Naoto
authors: N
authors: Nakamura
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D005234:Fatty Liver / Q000097:blood* / Q000503:physiopathology; D015870:Gene Expression; D006706:Homeostasis; D050356:Lipid Metabolism / Q000235:genetics; D008077:Lipoproteins, LDL / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009919:Orchiectomy; D011897:Random Allocation; D013739:Testosterone / Q000097:blood* / Q000172:deficiency; D014280:Triglycerides / Q000097:blood*
chemical_list: D004041:Dietary Fats; D008077:Lipoproteins, LDL; D014280:Triglycerides; D013739:Testosterone