1. Sterol Regulatory Element–Binding Protein-1c Mediates Increase of Postprandial Stearic Acid, a Potential Target for Improving Insulin Resistance, in Hyperlipidemia
- Author
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Changhao Sun, Liyan Liu, Lixin Na, Ying Li, Xia Chu, Songtao Li, and Huimin Lu
- Subjects
Male ,medicine.medical_specialty ,Fatty Acid Elongases ,Endocrinology, Diabetes and Metabolism ,Palmitic Acid ,Hyperlipidemias ,Pathophysiology ,Palmitic acid ,Mice ,chemistry.chemical_compound ,Insulin resistance ,Downregulation and upregulation ,Acetyltransferases ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Humans ,Gene Silencing ,Original Research ,chemistry.chemical_classification ,biology ,Fatty acid ,Middle Aged ,Postprandial Period ,medicine.disease ,Mice, Inbred C57BL ,Fatty acid synthase ,Postprandial ,Endocrinology ,Gene Expression Regulation ,Liver ,chemistry ,biology.protein ,Sterol Regulatory Element Binding Protein 1 ,Female ,lipids (amino acids, peptides, and proteins) ,Stearic acid ,Fatty Acid Synthases ,Insulin Resistance ,Stearic Acids ,Acetyl-CoA Carboxylase - Abstract
Elevated serum free fatty acids (FFAs) levels play an important role in the development of insulin resistance (IR) and diabetes. We investigated the dynamic changes and the underlying regulatory mechanism of postprandial FFA profile in hyperlipidemia (HLP) and their relation with insulin sensitivity in both humans and mice. We found that serum stearic acid (SA) is the only fatty acid that is increased dramatically in the postprandial state. The elevation of SA is due to increased insulin-stimulated de novo synthesis mediated by sterol regulatory element–binding protein-1c (SREBP-1c)/acetyl-CoA carboxylase/fatty acid synthase/elongation of long-chain fatty acid family member 6 (ELOVL6) and the elongation of palmitic acid (PA) catalyzed by ELOVL6. Downregulation of SREBP-1c or ELOVL6 by small interfering RNA can reduce SA synthesis in liver and serum SA level, followed by amelioration of IR in HLP mice. However, inhibition of SREBP-1c is more effective in improving IR than suppression of ELOVL6, which resulted in accumulation of PA. In summary, increased postprandial SA is caused by the insulin-stimulated SREBP-1c pathway and elongation of PA in HLP. Reduction of postprandial SA is a good candidate for improving IR, and SREBP-1c is potentially a better target to prevent IR and diabetes by decreasing SA.
- Published
- 2013