title: Differential regulation of dihydroceramide desaturase by palmitate versus monounsaturated fatty acids: implications for insulin resistance.
abstract: Much data implicate saturated fatty acids in deleterious processes associated with obesity, diabetes, and the metabolic syndrome. Many of these changes may be due to aberrant generation of bioactive lipids when saturated fatty acid availability to tissues is increased. On the other hand, studies are emerging that implicate the monounsaturated fatty acid oleate in protection from saturated fat mediated toxicity; however, the mechanisms are not well understood. Our data demonstrate a novel role for palmitate in increasing mRNA encoding DES1, which is the enzyme responsible for generating ceramide from its precursor dihydroceramide and thus controls synthesis of the bioactive lipid ceramide. Moreover, co-treatment with oleate prevented the increase in ceramide, and this occurred through attenuation of the increase in message and activity of DES1. Knockdown of DES1 also protected from palmitate-induced insulin resistance, and overexpression of this enzyme ameliorated the protective effect of oleate. Together, these findings provide insight into the mechanisms of oleate-mediated protection against metabolic disease and provide novel evidence for fatty acid-mediated regulation of a key enzyme of ceramide biosynthesis.
authors: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29403, USA.
authors: Wei
authors: W
authors: Hu
authors: Jessica
authors: J
authors: Ross
authors: Tuoyu
authors: T
authors: Geng
authors: Sarah E
authors: SE
authors: Brice
authors: L Ashley
authors: LA
authors: Cowart
mesh_terms: D000818:Animals; D002518:Ceramides / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D007333:Insulin Resistance; D008055:Lipids / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D010168:Palmitates / Q000737:chemistry*; D013107:Sphingolipids / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002518:Ceramides; D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D010168:Palmitates; D013107:Sphingolipids; D014280:Triglycerides; D010088:Oxidoreductases; C108138:dihydroceramide desaturase