title: Resistance to high-fat diet-induced obesity and insulin resistance in mice with very long-chain acyl-CoA dehydrogenase deficiency.
abstract: Mitochondrial fatty acid oxidation provides an important energy source for cellular metabolism, and decreased mitochondrial fatty acid oxidation has been implicated in the pathogenesis of type 2 diabetes. Paradoxically, mice with an inherited deficiency of the mitochondrial fatty acid oxidation enzyme, very long-chain acyl-CoA dehydrogenase (VLCAD), were protected from high-fat diet-induced obesity and liver and muscle insulin resistance. This was associated with reduced intracellular diacylglycerol content and decreased activity of liver protein kinase Cvarepsilon and muscle protein kinase Ctheta. The increased insulin sensitivity in the VLCAD(-/-) mice were protected from diet-induced obesity and insulin resistance due to chronic activation of AMPK and PPARalpha, resulting in increased fatty acid oxidation and decreased intramyocellular and hepatocellular diacylglycerol content.
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Zhang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Christianson
authors.forename: Zhen-Xiang
authors.initials: ZX
authors.lastname: Liu
authors.forename: Liqun
authors.initials: L
authors.lastname: Tian
authors.forename: Cheol Soo
authors.initials: CS
authors.lastname: Choi
authors.forename: Susanne
authors.initials: S
authors.lastname: Neschen
authors.forename: Jianying
authors.initials: J
authors.lastname: Dong
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wood
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology; D009765:Obesity / Q000209:etiology*; D047493:PPAR alpha / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D000074121:Protein Kinase C-theta; D011494:Protein Kinases / Q000378:metabolism
chemical_list: C011439:1,2-diacylglycerol; D004041:Dietary Fats; D004075:Diglycerides; D007328:Insulin; D007527:Isoenzymes; D047493:PPAR alpha; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D011494:Protein Kinases; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta; D000091162:AMP-Activated Protein Kinase Kinases
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