The Role of Stearoyl-CoA Desaturase in Body Weight Regulation
Section snippets
Role of SCD in Lipid Metabolism
Studies on scd1−/− mice have shown that loss of SCD function decreases the content of tissue triglycerides, cholesterol esters, wax esters, and alkyldiacylglycerols (Miyazaki et al. 2000 and 2001a). Additionally, scd1−/− mice have very low levels of triglycerides in the very low-density lipoprotein (VLDL) and low-density lipoprotein fractions, relative to normal animals (Miyazaki et al. 2000). The expression of scd2 in the liver of scd1−/− mice does not compensate for the scd1 deficiency, nor
SCD1 Deficiency Reduces Obesity of ob/ob Mice
Leptin is an adipocyte-derived liporegulatory hormone that controls lipid homeostasis in nonadipose tissues and was recently found to specifically repress scd1 gene expression and enzymatic activity of hepatic SCD (Cohen et al. 2002). In rodents, mutations in the ob gene can cause leptin deficiency. The ob/ob mice exhibit the full metabolic syndrome of obesity early in life, including hyperlipidemia; elevated free fatty acid levels; and steatosis of liver, heart, skeletal muscle, and pancreatic
SCD and Insulin Signaling
Obesity is often associated with resistance to insulin-stimulated glucose transport in muscles and adipose tissue and to insulin-stimulated suppression of glucose production in the liver (Haffner 2003). These events can, to some extent, be reversed by modest weight loss, which improves insulin signaling and protects pancreatic β cells. Therefore, why is obesity associated with insulin resistance and weight loss with improved insulin signaling? One of the proposed reasons is that excess lipids,
Conclusion
As outlined in this article, the recent studies on SCD provided many new insights into the biology of lipid metabolism and body weight regulation. SCD has been shown to be a critical enzyme in the synthesis of triglycerides, cholesterol esters, and wax esters. Mice with a targeted disruption of scd1 gene are considerably leaner and accumulate less fat than do their wild-type counterparts. Evidence points to direct antisteatotic effects of SCD deficiency on tissues, leading to a reduction in
Acknowledgements
The authors thank Pawel Dobrzyn, Harini Sampath, Seong-Ho Lee, and Makoto Miyazaki for their useful comments during the preparation of this review. This work has been supported by National Institutes of Health grant NIDDK-RO162388 (JMN) and American Heart Association Postdoctoral Fellowship 040051Z (AD).
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