Acute Exercise Improves High-Fat Diet-Induced Hepatic Insulin Resistance in Rats: Potential Role of AMP-Activated Protein Kinase
Abstract Number: 997-P
Authors: MARIE-SOLEIL GAUTHIER, RAYNALD BERGERON, MARTIN G. LATOUR, JEAN-MARC LAVOIE.
Institutions: Montr[eacute]al, QC, Canada; Rahway, NJ.
Results: Activation of AMPK with a single AICAR injection has been shown to enhance liver insulin sensitivity in high-fat fed rats (Iglesias et al., Diabetes 51: 2886-2894, 2002). Acute exercise has been shown to increase liver AMPK activity (Park et al., J Biol Chem 277: 32571-32577, 2002). The purpose of the present study was to determine whether an acute bout of treadmill running could improve high-fat diet-induced hepatic insulin resistance in rats and if this could be associated with liver AMPK activation. Male Wistar rats fed a standard (SD) or a high-fat (HF) diet for 3 weeks were submitted to a hyperinsulinemic euglycemic clamp with tracer (D-[3-3H]-glucose) infusion for the determination of endogenous glucose production (EGP). On the day of the experiment, high-fat fed rats were randomly assigned to a group that remained at rest (HF-Rest) or a group that was subjected to 30 min of treadmill running (HF-Ex). At steady-state during the clamp, glucose disappearance rate (Rd) was not different between the groups (P > 0.05). Glucose infusion rate (GIR) and suppression of EGP during the clamp were lower in HF-Rest compared to SD-Rest rats (P < 0.05 and P < 0.07, respectively) indicating a state of hepatic insulin resistance with high-fat feeding. However, GIR and suppression of EGP during the clamp were not different between HF-Ex compared to SD-Rest rats (P > 0.05) indicating an improvement in hepatic insulin sensitivity after acute exercise. Liver phospho-AMPK Thr172 levels were lower in HF-Rest compared to SD-Rest rats (P < 0.05). Liver phospho-AMPK Thr172 levels were completely restored to normal levels in HF-Ex rats (P > 0.05). In conclusion, an acute bout of exercise can improve high-fat diet-induced liver insulin resistance. Activation of liver AMPK could be, in part, responsible for the enhanced action of insulin with acute exercise.