Loss of stearoyl–CoA desaturase-1 function protects mice against adiposity

TLDR

Stearoyl‑CoA desaturase (SCD) catalyzes the synthesis of monounsaturated fatty acids such as oleate and palmitoleate, and mice possess several SCD isoforms (SCD1–3). SCD1‑deficient mice show reduced body fat, increased insulin sensitivity, resistance to diet‑induced obesity, higher energy expenditure and oxygen consumption, elevated plasma ketone bodies, lower insulin and leptin levels, and a shift toward lipid oxidation with down‑regulated triglyceride synthesis.

Abstract

Stearoyl–CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), which are components of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Several SCD isoforms ( SCD1 - 3 ) exist in the mouse. Here we show that mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased insulin sensitivity, and are resistant to diet-induced weight gain. The protection from obesity involves increased energy expenditure and increased oxygen consumption. Compared with the wild-type mice the SCD1 −/− mice have increased levels of plasma ketone bodies but reduced levels of plasma insulin and leptin. In the SCD1 −/− mice, the expression of several genes of lipid oxidation are up-regulated, whereas lipid synthesis genes are down-regulated. These observations suggest that a consequence of SCD1 deficiency is an activation of lipid oxidation in addition to reduced triglyceride synthesis and storage.