Retinol saturase modulates lipid metabolism and the production of reactive oxygen species

Arch Biochem Biophys. 2017 Nov 1:633:93-102. doi: 10.1016/j.abb.2017.09.009. Epub 2017 Sep 18.

Abstract

Retinol saturase (RetSat) catalyzes the saturation of double bonds of all-trans-retinol leading to the production of dihydroretinoid metabolites. Beside its role in retinoid metabolism, there is evidence that RetSat modulates the cellular response to oxidative stress and plays critical roles in adipogenesis and the accumulation of lipids. Here, we explore the relationship between RetSat, lipid metabolism and oxidative stress using in vitro and in vivo models with altered expression of RetSat. Our results reveal that RetSat is a potent modulator of the cellular response to oxidative stress and the generation of reactive oxygen species (ROS). The levels of reactive aldehydes products of lipid peroxidation, as measured based on thiobarbituric acid reactivity, are increased in RetSat overexpressing cells and, conversely, reduced in cells and tissues with reduced or absent expression of RetSat compared to controls. Despite increased weight gain, neutral lipid accumulation and alterations in hepatic lipid composition, RetSat-/- mice exhibit normal responses to insulin. In conclusion, our findings further expand upon the role of RetSat in oxidative stress and lipid metabolism and could provide insight in the significance of alterations of RetSat expression as observed in metabolic disorders.

Keywords: Adiposity; Lipid metabolism; Oxidative stress; Retinoid metabolism; Vitamin A.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cell Survival / drug effects
  • Embryo, Mammalian
  • Fatty Acids / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / enzymology*
  • Gene Expression
  • Insulin / pharmacology
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics*
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NIH 3T3 Cells
  • Oxidative Stress
  • Oxidoreductases Acting on CH-CH Group Donors / deficiency
  • Oxidoreductases Acting on CH-CH Group Donors / genetics*
  • Reactive Oxygen Species / metabolism*
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Fatty Acids
  • Insulin
  • Reactive Oxygen Species
  • Thiobarbituric Acid Reactive Substances
  • Oxidoreductases Acting on CH-CH Group Donors
  • retinol saturase (all trans retinol 13,14 reductase), mouse