Adipose tissue stearoyl-CoA desaturase mRNA is increased by obesity and decreased by polyunsaturated fatty acids

Abstract

Stearoyl-CoA desaturase (SCD) is a key regulatory enzyme in the synthesis of unsaturated fatty acids. Although regulation of hepatic SCD by obesity and polyunsaturated fatty acids (PUFA) has been well investigated, no studies have addressed whether similar regulation occurs in adipose tissue. We addressed these questions by feeding control (12% corn oil) and high-PUFA (48% corn oil) diets to lean and obese Zucker rats and analyzing SCD mRNA levels in adipose tissue and liver. We report that SCD mRNA content was dramatically elevated in adipose tissue of obese vs. lean rats on both diets and was significantly decreased by PUFA in both genotypes. Interestingly, we demonstrate that SCD expression was directly downregulated in a dose dependent manner by PUFA in 3T3-L1 adipocytes. We conclude that 1) obese Zucker rats overexpress the SCD gene in both liver and adipose tissue and 2) PUFA directly suppress SCD expression in adipocytes. Further studies will elucidate the mechanisms responsible for obesity- and PUFA-mediated regulation of SCD in adipose cells.

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

“…Thus, it is possible that loss of SCD1 function results in an increase in the concentration of a PPAR␣ activator, perhaps a lipid ligand. The contents of saturated fatty acids (C16:0 and C18:0) are increased, whereas the contents of the polyunsaturated fatty acids of the n-6 and n-3 are not changed in the liver of the SCD1Ϫ͞Ϫ mice (8,10). One possible mechanism for our observations is that the saturated fatty acids induce the signal that activates the PPAR␣ in the SCD1Ϫ͞Ϫ mice, but this has yet to be determined.…”

“…SCD expression is sensitive to dietary factors including polyunsaturated fatty acids, cholesterol and vitamin A, hormonal changes (i.e., insulin and glucagon), developmental processes, temperature changes, thiazolinediones, metals, alcohol, peroxisomal proliferators, and phenolic compounds (3). High SCD activity has been implicated in a wide range of disorders including diabetes, atherosclerosis, cancer, obesity, and viral infection (3,(8)(9)(10)(11)(12)(13).The existence of multiple SCD isoforms in mice (6, 14-18) and rats makes it difficult to determine the role of each isoform in lipid metabolism. New insights into the physiological role of the SCD1 gene and its endogenous products came from recent studies of the asebia mouse strains (ab j and ab 2j ) that have naturally occurring mutations in SCD1 (17-19) as well as a laboratory mouse model with a targeted disruption (SCD1Ϫ͞Ϫ) (6).…”

“…SCD expression is sensitive to dietary factors including polyunsaturated fatty acids, cholesterol and vitamin A, hormonal changes (i.e., insulin and glucagon), developmental processes, temperature changes, thiazolinediones, metals, alcohol, peroxisomal proliferators, and phenolic compounds (3). High SCD activity has been implicated in a wide range of disorders including diabetes, atherosclerosis, cancer, obesity, and viral infection (3,(8)(9)(10)(11)(12)(13).…”

Conjugated linoleic acid and obesity control: efficacy and mechanisms

“…Palmitoleate and oleate are the major monounsaturated fatty acids of membrane phospholipids and triglycerides found in differentiated 3T3-L1 adipocytes in vitro and mouse adipose tissue in vivo. 67 A proper ratio of saturated to unsaturated fatty acids is important in maintaining membrane fluidity; alteration of this ratio can influence a variety of physiological responses, including adiposity, 68 metabolic rate 69 and insulin sensitivity, 70 all of which are affected by CLA.…”

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

“…These fatty acids in the ester form are the major constituents of VLDL-TGs [18]. The saturated/monounsaturated fatty acid ratio modulates the composition of phospholipids in cell membranes and affects membrane fluidity; differences in this ratio are associated with a number of diseases, including diabetes and obesity [19][20][21][22][23].…”