high fat diet-induced changes in mouse muscle mitochondrial phospholipids do not impair mitochondrial respiration despite insulin resistance高脂肪食源性老鼠肌肉线粒体磷脂的变化不影响线粒体呼吸尽管胰岛素抵抗.pdfVIP

High Fat Diet-Induced Changes in Mouse Muscle Mitochondrial Phospholipids Do Not Impair Mitochondrial Respiration Despite Insulin Resistance 1. 1,2 . 1,2 2,3 Joris Hoeks , Janneke de Wilde * , Martijn F. M. Hulshof , Sjoerd A. A. van den Berg , Gert Schaart4, Ko Willems van Dijk1,3,5, Egbert Smit1,2, Edwin C. M. Mariman1,2 1 Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands, 2 Top Institute Food and Nutrition, Nutrigenomics Consortium, Wageningen, The Netherlands, 3 Department of Human Genetics, University Medical Center Leiden, Leiden, The Netherlands, 4 Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands, 5 Department of Internal Medicine, University Medical Center Leiden, Leiden, The Netherlands Abstract Background: Type 2 diabetes mellitus and muscle insulin resistance have been associated with reduced capacity of skeletal muscle mitochondria, possibly as a result of increased intake of dietary fat. Here, we examined the hypothesis that a prolonged high-fat diet consumption (HFD) increases the saturation of muscle mitochondrial membrane phospholipids causing impaired mitochondrial oxidative capacity and possibly insulin resistance. Methodology: C57BL/6J mice were fed an 8-week or 20-week low fat diet (10 kcal%; LFD) or HFD (45 kcal%). Skeletal muscle mitochondria were isolated and fatty acid (FA) composition of skeletal muscle mitochondrial phospholipids was analyzed by thin-layer chromatography followed by GC. High-resolution respirometry was used to assess oxidation o