title: Impaired fat oxidation after a single high-fat meal in insulin-sensitive nondiabetic individuals with a family history of type 2 diabetes.
abstract: Individuals with insulin resistance and type 2 diabetes have an impaired ability to switch appropriately between carbohydrate and fatty acid oxidation. However, whether this is a cause or consequence of insulin resistance is unclear, and the mechanism(s) involved in this response is not completely elucidated. Whole-body fat oxidation and transcriptional regulation of genes involved in lipid metabolism in skeletal muscle were measured after a prolonged fast and after consumption of either high-fat (76%) or high-carbohydrate (76%) meals in individuals with no family history of type 2 diabetes (control, n = 8) and in age- and fatness-matched individuals with a strong family history of type 2 diabetes (n = 9). Vastus lateralis muscle biopsies were performed before and 3 h after each meal. Insulin sensitivity and fasting measures of fat oxidation were not different between groups. However, subjects with a family history of type 2 diabetes had an impaired ability to increase fatty acid oxidation in response to the high-fat meal (P < 0.05). This was related to impaired activation of genes involved in lipid metabolism, including those for peroxisome proliferator-activated receptor coactivator-1alpha (PGC1alpha) and fatty acid translocase (FAT)/CD36 (P < 0.05). Of interest, adiponectin receptor-1 expression decreased 23% after the high-fat meal in both groups, but it was not changed after the high-carbohydrate meal. In conclusion, an impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals. PGC1alpha and FAT/CD36 are likely candidates in mediating this response.
authors: Diabetes and Obesity Program, Garvan Institute of Medical Research, New South Wales, Australia. l.heilbronn@garvan.org.au
authors: Leonie K
authors: LK
authors: Heilbronn
authors: Søren
authors: S
authors: Gregersen
authors: Deepali
authors: D
authors: Shirkhedkar
authors: Dachun
authors: D
authors: Hu
authors: Lesley V
authors: LV
authors: Campbell
mesh_terms: D000328:Adult; D001706:Biopsy; D018955:CD36 Antigens / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D005223:Fats / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006262:Health; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010375:Pedigree; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D022722:Thermogenesis / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D004041:Dietary Fats; D005223:Fats; D006360:Heat-Shock Proteins; D007328:Insulin; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors