Abstract
Citrus flavonoids have been shown to decrease plasma lipid levels, improve glucose tolerance, and attenuate obesity. One possible mechanism underlying these physiological effects is reduction of hepatic levels of the mRNA for stearoyl-CoA desaturase-1 (SCD1), since repression of this enzyme reduces hyperlipidemia and adiposity. Here, we show that citrus flavonoids of two structural classes reduce SCD1 mRNA concentrations in a dose-dependent manner in rat primary hepatocytes. This is the first demonstration of repression of SCD1 by citrus flavonoids, either in vivo or in cultured cells. Furthermore, it is the first use of freshly-isolated hepatocytes from any animal to examine citrus flavonoid action at the mRNA level. This study demonstrates that regulation of SCD1 gene expression may play a role in control of obesity by citrus flavonoids and that rat primary hepatocytes are a physiologically-relevant model system for analyzing the molecular mechanisms of flavonoid action in the liver.
Highlights
Understanding the molecular mechanisms that regulate lipid synthesis and deposition is of paramount importance, since obesity increases the risk of prevalent, lifethreatening diseases such as diabetes and atherosclerosis
An intriguing model proposes that obesity is attenuated by lowering the amount of hepatic and/or adipose stearoyl-CoA desaturase-1 (SCD1), the rate-limiting enzyme in biosynthesis of monounsaturated fatty acids, which are preferred for triglyceride assembly [1]
Citrus Polymethoxylated Flavones (PMFs) regulation of SCD1 mRNA because of the hypothesis that repression of SCD1 plays a key role in control of obesity and diabetes [1], and because of the recent report of citrus flavonoid attenuation of adiposity and insulin resistance in mice fed a high-fat diet [20]
Summary
Understanding the molecular mechanisms that regulate lipid synthesis and deposition is of paramount importance, since obesity increases the risk of prevalent, lifethreatening diseases such as diabetes and atherosclerosis. An intriguing model proposes that obesity is attenuated by lowering the amount of hepatic and/or adipose stearoyl-CoA desaturase-1 (SCD1), the rate-limiting enzyme in biosynthesis of monounsaturated fatty acids, which are preferred for triglyceride assembly [1]. This model is supported by gene knockout or knockdown studies, in which reduction of SCD1 mRNA levels restricted adiposity, insulin resistance, and hepatic lipid accumulation in rodents [2,3,4,5].
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