Resistance to high-fat diet-induced obesity and insulin resistance in mice with very long-chain acyl-CoA dehydrogenase deficiency.
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.
Zhang
Dongyan
D
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Christianson
Jennifer
J
Liu
Zhen-Xiang
ZX
Tian
Liqun
L
Choi
Cheol Soo
CS
Neschen
Susanne
S
Dong
Jianying
J
Wood
Philip A
PA
Shulman
Gerald I
GI
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
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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