Hepatocyte-specific Selenoi deficiency predisposes mice to hepatic steatosis and obesity

FASEB J. 2024 Jun 15;38(11):e23717. doi: 10.1096/fj.202400575RR.

Abstract

Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise function of Selenoi in the liver remains elusive. In the study, we generated hepatocyte-specific Selenoi conditional knockout (cKO) mice on a high-fat diet to identify the physiological function of Selenoi. The cKO group exhibited a significant increase in body weight, with a 15.6% and 13.7% increase in fat accumulation in white adipose tissue (WAT) and the liver, respectively. Downregulation of the lipolysis-related protein (p-Hsl) and upregulation of the adipogenesis-related protein (Fasn) were observed in the liver of cKO mice. The cKO group also showed decreased oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (p < .05). Moreover, various metabolites of the steroid hormone synthesis pathway were affected in the liver of cKO mice. A potential cascade of Selenoi-phosphatidylethanolamine-steroid hormone synthesis might serve as a core mechanism that links hepatocyte-specific Selenoi cKO to biochemical and molecular reactions. In conclusion, we revealed that Selenoi inhibits body fat accumulation and hepatic steatosis and elevates energy consumption; this protein could also be considered a therapeutic target for such related diseases.

Keywords: energy metabolism; high‐fat diet; obesity; selenoprotein I; steroid hormone synthesis pathway.

MeSH terms

  • Adipose Tissue, White / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Energy Metabolism
  • Ethanolaminephosphotransferase* / genetics
  • Fatty Liver* / etiology
  • Fatty Liver* / genetics
  • Fatty Liver* / metabolism
  • Fatty Liver* / pathology
  • Hepatocytes* / metabolism
  • Lipid Metabolism
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity* / etiology
  • Obesity* / genetics
  • Obesity* / metabolism
  • Selenoproteins* / genetics
  • Selenoproteins* / metabolism

Substances

  • Selenoproteins
  • SELENOI protein, human
  • Ethanolaminephosphotransferase