Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats.
High levels of dietary fat may contribute to both insulin resistance and obesity in humans but evidence is limited. The euglycemic clamp technique combined with tracer administration was used to study insulin action in vivo in liver and individual peripheral tissues after fat feeding. Basal and nutrient-stimulated metabolic rate was assessed by open-circuit respirometry. Adult male rats were pair-fed isocaloric diets high in either carbohydrate (69% of calories; HiCHO) or fat (59% of calories; HiFAT) for 24 +/- 1 days. Feeding of the HiFAT diet resulted in a greater than 50% reduction in net whole-body glucose utilization at midphysiological insulin levels (90-100 mU/l) due to both reduced glucose disposal and, to a lesser extent, failure to suppress liver glucose output. Major suppressive effects of the HiFAT diet on glucose uptake were found in oxidative skeletal muscles (29-61%) and in brown adipose tissue (BAT; 78-90%), the latter accounting for over 20% of the whole-body effect. There was no difference in basal metabolic rate but thermogenesis in response to glucose ingestion was higher in the HiCHO group. In contrast to their reduced BAT weight, the HiFAT group accumulated more white adipose tissue, consistent with reduced energy expenditure. HiFAT feeding also resulted in major decreases in basal and insulin-stimulated conversion of glucose to lipid in liver (26-60%) and brown adipose tissue (88-90%) with relatively less effect in white adipose (0-43%). We conclude that high-fat feeding results in insulin resistance due mainly to effects in oxidative skeletal muscle and BAT.(ABSTRACT TRUNCATED AT 250 WORDS)
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000209:etiology*; D051381:Rats; D011919:Rats, Inbred Strains
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D005947:Glucose