Short-term high fat-feeding results in morphological and metabolic adaptations in the skeletal muscle of C57BL/6J mice.
The prevalence of the metabolic syndrome (MS) is rapidly increasing all over the world. Consequently, there is an urgent need for more effective intervention strategies. Both animal and human studies indicate that lipid oversupply to skeletal muscle can result in insulin resistance, which is one of the characteristics of the MS. C57BL/6J mice were fed a low-fat (10 kcal%) palm oil diet or a high-fat (45 kcal%; HF) palm oil diet for 3 or 28 days. By combining transcriptomics with protein and lipid analyses we aimed to better understand the molecular events underlying the early onset of the MS. Short-term HF feeding led to altered expression levels of genes involved in a variety of biological processes including morphogenesis, energy metabolism, lipogenesis, and immune function. Protein analysis showed increased levels of the myosin heavy chain, slow fiber type protein, and the complexes I, II, III, IV, and V of the oxidative phosphorylation. Furthermore, we observed that the main mitochondrial membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, contained more saturated fatty acids. Altogether, these results point to a morphological as well as a metabolic adaptation by promoting a more oxidative fiber type. We hypothesize that after this early positive adaptation, a continued transcriptional downregulation of genes involved in oxidative phosphorylation will result in decreased oxidative capacity at a later stage. Together with increased saturation of phospholipids of the mitochondrial membrane this can result in decreased mitochondrial function, which is a hallmark observed in insulin resistance and Type 2 diabetes.
de Wilde
Janneke
J
Nutrigenomics Consortium, Top Institute Food and Nutrition, Wageningen, the Netherlands. j.dewilde@hb.unimaas.nl
Mohren
Ronny
R
van den Berg
Sjoerd
S
Boekschoten
Mark
M
Dijk
Ko Willems-Van
KW
de Groot
Philip
P
Müller
Michael
M
Mariman
Edwin
E
Smit
Egbert
E
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage* / Q000633:toxicity; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D000073878:Palm Oil; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010938:Plant Oils / Q000008:administration & dosage* / Q000633:toxicity; D011897:Random Allocation; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors
D001786:Blood Glucose; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D007328:Insulin; D009124:Muscle Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010938:Plant Oils; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000073878:Palm Oil; D005947:Glucose