Effects of Acute Exercise Combined with Calorie Restriction Initiated Late-in-Life on Insulin Signaling, Lipids and Glucose Uptake in Skeletal Muscle from Old Rats.

We evaluated effects of calorie restriction (CR: consuming 60-65% of ad libitum [AL] intake) initiated late-in-life with or without acute exercise on insulin-stimulated glucose uptake (ISGU) of skeletal muscle by studying 4 groups of 26-month-old rats: sedentary-AL, sedentary-CR (8-week duration), 3-hours post-exercise (3hPEX)-AL and 3hPEX-CR. ISGU was determined in isolated epitrochlearis muscles incubated ±insulin. Muscles were assessed for signaling proteins (immunoblotting) and lipids (mass spectrometry). ISGU from sedentary-CR and 3hPEX-AL exceeded sedentary-AL; 3hPEX-CR exceeded all other groups. Akt (Ser473, Thr308) and Akt substrate of 160 kDa (AS160; Ser588, Thr642, Ser704) phosphorylation levels tracked with ISGU. Among the 477 lipids detected, 114 were altered by CR (including reductions in 15 of 25 acylcarnitines), and 27 were altered by exercise (including reductions in 18 of 22 lysophosphatidylcholines) with only 6 lipids overlapping between CR and exercise. ISGU significantly correlated with 23 lipids, including: acylcarnitine 20:1 (r=0.683), lysophosphatidylethanolamine19:0 (r=-0.662), acylcarnitine 24:0 (r=0.611), and plasmenyl-phosphatidylethanolamine 37:5 (r=-0.603). Muscle levels of ceramides (a lipid class previously linked to insulin resistance) were not altered by CR and/or exercise nor significantly correlated with ISGU, implicating other mechanisms (which potentially involve other lipids identified in this study) for greater ISGU and Akt and AS160 phosphorylation with these interventions.