Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice

Arch Biochem Biophys. 2017 May 15;622:47-58. doi: 10.1016/j.abb.2017.03.007. Epub 2017 Mar 22.

Abstract

Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor- and lipid/lipoprotein metabolism-related gene expression. Interestingly, we found that hepatic steatosis was accompanied by markedly elevated plasma testosterone levels in male ArKO mice but not in female ArKO mice. Plasma lipoprotein profiles exhibited concurrent decreases in LDL- and small dense LDL-triglyceride (TG) levels in male ArKO mice. Moreover, male mice, but not female mice, exhibited marked elevations in androgen receptor (AR), sterol regulatory element-binding protein 1 (SREBP1), and CD36 expression. These results strongly suggest that Cyp19 gene disruption, which induces a sexually dimorphic response and high plasma testosterone levels in male mice, also induces hepatic steatosis.

Keywords: Aromatase; Cyp19; PPARα; SREBP1; Steatosis; Testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatase / analysis
  • Aromatase / genetics*
  • CD36 Antigens / analysis
  • CD36 Antigens / genetics
  • Estrogens / metabolism
  • Fatty Liver / blood
  • Fatty Liver / genetics*
  • Fatty Liver / metabolism
  • Fatty Liver / pathology*
  • Female
  • Lipid Metabolism*
  • Lipoproteins / blood*
  • Lipoproteins / metabolism
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Mice
  • Mice, Knockout
  • Receptors, Androgen / analysis
  • Receptors, Androgen / genetics
  • Sterol Regulatory Element Binding Protein 1 / analysis
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Testosterone / blood*
  • Testosterone / metabolism
  • Up-Regulation

Substances

  • CD36 Antigens
  • Estrogens
  • Lipoproteins
  • Receptors, Androgen
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Testosterone
  • Aromatase