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

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.

Fig 1.

Body weight of male and female wild-type and SCD1−/− mice fed a chow or high-fat diet.

Fig 2.

(A) Abdominal view of the fat pad under the skin in 23-week-old male wild-type and SCD1−/− mice. (B) Epididymal fat pads and liver isolated from the wild-type and SCD1−/− mice on a chow diet. (C) Epididymal fat pads and liver isolated from the wild-type and SCD1−/− mice on a high-fat diet. (Bar = 1 cm.) (D) Fat pad weights from mice fed chow and high-fat diets.

Fig 3.

(A) Metabolic rate and oxygen consumption of male mice on a chow diet. (B) Gender-adjusted, normalized total oxygen consumption over a 23-h period. Error bars denote SE.

Fig 4.

(A) Expression levels of lipid oxidation (Left) and lipid synthesis (Right) genes between wild-type and SCD1−/− mice. (B) Quantitative reverse-transcription–PCR of FIAF and FAS gene expression, relative to wild-type mice. 18S RNA was used as a normalization control. (C) Northern blot analysis of lipid oxidation genes and lipid synthesis genes (SREBP-1, FAS, and GPAT) in the wild-type and SCD1−/− mice.

Fig 5.

Plasma glucose levels during the glucose tolerance test of male and female wild-type and SCD1−/− mice.