DIET-INDUCED MUSCLE INSULIN-RESISTANCE IN RATS IS AMELIORATED BY ACUTE DIETARY-LIPID WITHDRAWAL OR A SINGLE BOUT OF EXERCISE - PARALLEL RELATIONSHIP BETWEEN INSULIN STIMULATION OF GLUCOSE-UPTAKE AND SUPPRESSION OF LONG-CHAIN FATTY ACYL-COA

Chronic high-fat feeding in rats induces profound whole-body insulin r esistance, mainly due to effects in oxidative skeletal muscle. The mec hanisms of this reaction remain unclear, but local lipid availability has been implicated. The aim of this study was to examine the influenc e of three short-term physiological manipulations intended to lower mu scle lipid availability on insulin sensitivity in high-fat-fed rats. A dult male Wistar rats fed a high-fat diet for 3 weeks were divided int o four groups the day before the study: one group was fed the normal d aily high-fat meal (FM); another group was fed an isocaloric low-fat h igh-glucose meal (GM); a third group was fasted overnight (NM); and a fourth group underwent a single bout of exercise (2-h swim), then were fed the normal high-fat meal (EX). In vivo insulin action was assesse d using the hyperinsulinemic glucose clamp (plasma insulin 745 pmol/l, glucose 7.2 mmol/l). Prior exercise, a single low-fat meal, or fastin g all significantly increased insulin-stimulated glucose utilization, estimated at either the whole-body level (P < 0.01 vs. FM) or in red q uadriceps muscle (EX 18.2, GM 28.1, and NM 19.3 vs. FM 12.6 +/- 1.1 mu mol.100.g(-1).min(-1); P < 0.05), as well as increased insulin suppre ssibility of muscle total long-chain fatty acyl-CoA (LC-CoA), the meta bolically available form of fatty acid (EX 24.0, GM 15.5, and NM 30.6 vs. FM 45.4 nmol/g; P < 0.05). There was a strong inverse correlation between glucose uptake and LC-CoA in red quadriceps during the clamp ( r = -0.7, P = 0.001). Muscle triglyceride was significantly reduced by short-term dietary lipid withdrawal (GM -22 and NM -24% vs. FM; P < 0 .01), but not prior exercise. We concluded that muscle insulin resista nce induced by high-fat feeding is readily ameliorated by three indepe ndent, short-term physiological manipulations. The data suggest that i nsulin resistance is an important factor in the elevated muscle lipid availability induced by chronic high-fat feeding.