A Single Session of Endurance Exercise Protects Against Fatty-Acid Induced Insulin Resistance

Abstract

Although the insulin sensitizing effects of exercise are well described, it is not known if a single session of exercise can protect against fatty acid-induced insulin resistance. PURPOSE: Determine if performing a single session of exercise prevents or attenuates the reduction in insulin sensitivity found in response to an elevation in plasma fatty acid concentration. METHODS: Five, lean healthy women (26±2 yr, BMI=21.7±0.8 kg·m−2) performed two separate trials, each lasting 2d. In both trials, insulin sensitivity (Si) was measured in the morning of Day 1 using an intravenous glucose tolerance test (IVGTT). In the afternoon of Day 1, subjects either remained sedentary (SED) or exercised (EX) for 90 min at ∼65% VO2peak. During both trials, a 20% lipid emulsion with heparin was started (0.11 g fat·kg-1·h−1) at 1900h and was continued for 17h until the end of the trial on Day 2. Blood samples were taken overnight for measurement of plasma fatty acid concentrations and indirect calorimetry was used to measure whole-body fatty acid oxidation. In the morning of Day 2, a muscle biopsy was obtained to measure basal phosphorylation of c-Jun N-terminal kinase (p-JNK), which is known to play a key role in fatty acid-induced inhibition of insulin signaling. A second IVGTT was performed after the muscle biopsy. RESULTS: The lipid infusions increased overnight plasma fatty acid concentration ∼2. 5-fold (p<0.01) compared with fasting levels in both SED and EX, and plasma fatty acid concentration during the IVGTT on Day 2 was ∼4-fold higher than Day 1 (p<0.002). During SED, the lipid infusion reduced Si by ∼25% (S1: 4.0±0.6 vs. 3.0±0.4 μU·min−1mL−1 for Day 1 and Day 2, respectively, p<0.05). However, this fatty acid-induced reduction in Si was completely prevented in EX. In fact, despite the elevated fatty acid availability, EX significantly increased Si by∼25% (4.0±0.7vs. 5.1±0.7 μU·min−1·mL−1 for Day 1 and Day 2, respectively, p<0.05). Furthermore, fatty acid oxidation throughout the lipid infusion was ∼40% higher in EX compared with SED (p<0.006) and basal muscle p-JNK (normalized to total JNK abundance) was ∼60% lower in EX compared with SED (p=0.07). CONCLUSIONS: Fatty acid-induced impairment of insulin sensitivity can be completely prevented by a single session of endurance exercise. This protective effect of exercise may be mediated through enhanced partitioning of excess fatty acids toward oxidation, and a resultant reduction in the phosphorylation/activation of inflammatory factors, such as JNK, which are known to impair insulin signaling.