Stearoyl-CoA desaturase (SCD) is a regulatory enzyme in lipogenesis, catalyzing the rate-limiting step in the overall de novo synthesis of monounsaturated fatty acids mainly oleate and palmitoleate from stearoyl- and palmitoyl-CoA, respectively. SCD1 deficiency activates metabolic pathways that promote fatty acid β-oxidation and decrease lipogenesis in liver and skeletal muscles. SCD1-/- mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis. In the present study, using the SCD1-/- mouse model, we have shown that SCD1 deficiency causes decrease in fatty acids transport and oxidation in the heart. The concentrations of free fatty acids (FFA) and triglycerides (TG) in blood plasma were significantly lower in SCD1-/- mice compared to wild-type controls. To estimate the rate of the membrane fatty acid transport into the heart of SCD1-/- mice we measured the level of both fatty acid translocase (FAT)/CD36 and fatty acid transport protein (FATP) in isolated cardiomyocyte membranes by Western blotting. The contents of the both proteins were significantly lower in the heart of SCD1-/- mice compared to wild-type mice. Decreased rate of membrane transport of fatty acids into the heart was associated with reduced intracellular lipid levels. The contents of FFA and TG were decreased by 30.6 and 41.9 %, respectively, in the heart of SCD1-/- mice in comparison to wild type mice. The rate of fatty acid oxidation is controlled by the rate of their transfer into the mitochondria through carnitine palmitoyltransferase 1 (CPT1). Both CPT1 protein level and activity were significantly decreased in the heart of SCD1-/- mice in comparison to wild type controls. Consequently, also the rate of palmitoyl-CoA oxidation in the heart of SCD1-/- mice was 37.1% lower compared to wild-type mice. Because FFA and TG contents in both blood plasma and cardiomyocytes are significantly reduced in SCD1-/- mice, it is concluded that SCD1 deficiency, by increasing whole body energy expenditure and reducing lipogenesis, decreases fatty acids availability for utilization by the heart.

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1. Molecular mechanism of lipid-induced insulin resistance – the role of stearoyl-CoA desaturase