Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism

Wicks Shawna E.; Vandanmagsar Bolormaa; Haynie Kimberly R.Fuller Scott E.Warfel Jaycob D.Stephens Jacqueline M.Wang MiaoHan XianlinZhang JingyingNoland Robert C.Mynatt Randall L.

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Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism

机译：Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism

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The correlations between intramyocellular lipid (IMCL), decreased fatty acid oxidation (FAO), and insulin resistance have led to the hypothesis that impaired FAO causes accumulation of lipotoxic intermediates that inhibit muscle insulin signaling. Using a skeletal muscle-specific carnitine palmitoyltransferase-1 KO model, we show that prolonged and severe mitochondrial FAO inhibition results in increased carbohydrate utilization, along with reduced physical activity; increased circulating nonesterified fatty acids; and increased IMCLs, diacylglycerols, and ceramides. Perhaps more importantly, inhibition of mitochondrial FAO also initiates a local, adaptive response in muscle that invokes mitochondrial biogenesis, compensatory peroxisomal fat oxidation, and amino acid catabolism. Loss of its major fuel source (lipid) induces an energy deprivation response in muscle coordinated by signaling through AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha) to maintain energy supply for locomotion and survival. At the whole-body level, these adaptations result in resistance to obesity.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第25期|E3300-E3309|共10页
作者
Wicks Shawna E.; Vandanmagsar Bolormaa; Haynie Kimberly R.Fuller Scott E.Warfel Jaycob D.Stephens Jacqueline M.Wang MiaoHan XianlinZhang JingyingNoland Robert C.Mynatt Randall L.;
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作者单位

Pennington Biomed Res Ctr, Gene Nutrient Interact Lab, Baton Rouge, LA 70808 USA;

Pennington Biomed Res Ctr, Adipocyte Biol Lab, Baton Rouge, LA 70808 USA;

Sanford Burnham Med Res Inst, Orlando, FL 32827 USAPennington Biomed Res Ctr, Transgen Core Facil, Baton Rouge, LA 70808 USAPennington Biomed Res Ctr, Skeletal Muscle Metab Lab, Baton Rouge, LA 70808 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
carnitine palmitoyltransferase; muscle; fatty acid; lipid; carbohydrate;

Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism

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