title: Sterol regulatory element-binding protein-1c mediates increase of postprandial stearic acid, a potential target for improving insulin resistance, in hyperlipidemia.
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.
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Hei Longjiang Province, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chu
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.forename: Lixin
authors.initials: L
authors.lastname: Na
authors.forename: Huimin
authors.initials: H
authors.lastname: Lu
authors.forename: Songtao
authors.initials: S
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000123:Acetyltransferases / Q000235:genetics; D000818:Animals; D000081031:Fatty Acid Elongases; D064429:Fatty Acid Synthases; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D019308:Palmitic Acid / Q000378:metabolism; D019518:Postprandial Period / Q000235:genetics / Q000502:physiology*; D013229:Stearic Acids / Q000097:blood* / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000630955:ELOVL6 protein, human; C000630968:Elovl6 protein, mouse; D013229:Stearic Acids; D051780:Sterol Regulatory Element Binding Protein 1; D019308:Palmitic Acid; C031183:stearic acid; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase