Exercise restores insulin, but not adiponectin, response in skeletal muscle of high-fat fed rodents

Gulli RA, Tishinsky JM, MacDonald T, Robinson LE, Wright DC, Dyck DJ. Exercise restores insulin, but not adiponectin, response in skeletal muscle of high-fat fed rodents. Am J Physiol Regul Integr Comp Physiol 303: R1062-R1070, 2012. First published October 10, 2012; doi:10.1152/ajpregu.00176.2012.-High-fat (HF) diets impair skeletal muscle response to the insulin-sensitizing adipokine adiponectin (Ad) in rodents, preceding the development of insulin resistance. Skeletal muscle insulin response in HF-fed rats can be restored with chronic exercise; whether recovery of skeletal muscle Ad response is necessary for the exercise-induced recovery of insulin-stimulated glucose transport is not known. In the current study, insulin and Ad resistance were induced in rodents with 4 wk of HF feeding (HF4; low-fat fed animals used as control). Rats were then treadmill-exercised (HF5EX1, HF6EX2) or supplemented orally with the pharmacological agent beta-guadinoproprionic acid (GPA; HF(5)GPA(1), HF(6)GPA(2)) for 1 or 2 wk with continued HF feeding. Insulin and Ad responses (glucose transport and palmitate oxidation, respectively) were assessed 48 h after the last exercise bout ex vivo in isolated solei. Insulin response was impaired following 4 wk of HF feeding and improved with 1 and 2 wk of exercise and beta-GPA supplementation (HF5EX1, HF6EX2, HF(5)GPA(1), and HF(6)GPA(2)). The recovery of insulin response generally coincided with improved Akt Thr(308) phosphorylation in HF(5)GPA(1), HF6EX2, and HF(6)GPA(2), although not in HF5EX1. Ad-stimulated palmitate oxidation was not restored with either treatment. Total protein contents of AdipoR1, AdipoR2, APPL1, and APPL2, as well as total and phosphorylated AMPK and ACC were unaltered by diet, exercise, and beta-GPA at the assessed time points. We conclude that the exercise and pharmacologically (beta-GPA)-induced recovery of skeletal muscle insulin response after HF feeding is not dependent on the restoration of Ad response, as assessed ex vivo.