Stearoyl‐CoA desaturase: a new therapeutic target of liver steatosis

Abstract

Stearoyl-CoA desaturase (SCD) is the rate limiting enzyme catalyzing the biosynthesis of monounsaturated fatty acids, mainly oleate and palmitoleoate, which are used as substrates for the synthesis of triglycerides, wax esters, cholesterol esters, and phospholipids. Recent studies have shown that SCD1, the main SCD isoform expressed in liver, is a key player in the regulation of lipid metabolism. SCD1 deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis. SCD1 was found to be specifically repressed during leptin-mediated weight loss and leptin-deficient ob/ob mice lacking SCD1 showed markedly reduced adiposity, despite higher food intake. In addition, SCD1 deficiency completely corrects the hypometabolic phenotype and hepatic steatosis of ob/ob mice, and attenuates fasting-induced liver steatosis in peroxisome proliferator-activated receptor-a -deficient mice. Consequently, increased SCD activity has been found in humans and animals which accumulate significant amounts of lipids in liver, whereas SCD1 deficiency ameliorates both high-fat diet induced and genetically induced hepatic steatosis. Much evidence indicates that the direct anti-steatotic effect of SCD1 deficiency stems from increased fatty acid oxidation and reduced lipid synthesis. In this review we discuss our current understanding of the role of SCD1 in regulation of hepatic lipid partitioning and test the hypothesis that pharmacological manipulation of SCD might be of benefit in the treatment of non-alcoholic fatty liver disease. Drug Dev.

Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases

“…Of note, rising FFA (C16:1) is able to increase insulin sensitivity [45]. SCD, with its main isoform SCD1 expressed in liver [46], was activated in CHB, CIR and HCC, characterized by reversely decreasing ratio of saturated FFAs to monounsaturated FFAs (Fig. 3).…”

“…3). The benefit of SCD1 deficiency to increase FAO and inhibit lipid synthesis has been reviewed [46], concluding that increased SCD activity in humans and animals is related to significantly accumulated lipids in liver [46]. And the significantly decreased ratio of saturated FFAs to monounsaturated FFAs in CIR and HCC compared with CHB indicated that the SCD activity increased with the severity of liver diseases.…”

Stearoyl‐CoA desaturase: A novel control point of lipid metabolism and insulin sensitivity

“…Mice with a targeted disruption in the SCD1 gene have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity [7][8][9][10]. SCD1 was found to be specifically repressed during leptin-mediated weight loss, and leptin-deficient ob/ob mice lacking SCD1 showed markedly reduced adiposity, despite higher food intake [11].…”

Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart

“…Stearoyl-CoA desaturase (SCD), the rate-limiting enzyme in the biosynthesis of monounsaturated FAs, has recently been shown to be a critical control point in regulation of liver and skeletal muscle metabolism (12,13,27). Studies of a mouse model with a targeted disruption of the SCD1 gene have provided evidence that lack of SCD1 function increases energy expenditure and basal thermogenesis (27) and significantly reduces body adiposity (23,29).…”