Human skeletal muscle metabolic responses to 6 days of high-fat overfeeding are associated with dietary n-3PUFA content and muscle oxidative capacity

Abstract

Understanding human physiological responses to high-fat energy excess (HFEE) may help combat the development of metabolic disease. We aimed to investigate the impact of manipulating the n-3PUFA content of HFEE diets on whole-body and skeletal muscle markers of insulin sensitivity. Twenty healthy males were overfed (150% energy, 60% fat, 25% carbohydrate, 15% protein) for 6 d. One group (n = 10) received 10% of fat intake as n-3PUFA rich fish oil (HF-FO), and the other group consumed a mix of fats (HF-C). Oral glucose tolerance tests with stable isotope tracer infusions were conducted before, and following, HFEE, with muscle biopsies obtained in basal and insulin-stimulated states for measurement of membrane phospholipids, ceramides, mitochondrial enzyme activities, and PKB and AMPK alpha 2 activity. Insulin sensitivity and glucose disposal did not change following HFEE, irrespective of group. Skeletal muscle ceramide content increased following HFEE (8.5 +/- 1.2 to 12.1 +/- 1.7 nmol/mg, p = .03), irrespective of group. No change in mitochondrial enzyme activity was observed following HFEE, but citrate synthase activity was inversely associated with the increase in the ceramide content (r=-0.52,p = .048). A time by group interaction was observed for PKB activity (p = .003), with increased activity following HFEE in HF-C (4.5 +/- 13.0mU/mg) and decreased activity in HF-FO (-10.1 +/- 20.7 mU/mg) following HFEE. Basal AMPK alpha 2 activity increased in HF-FO (4.1 +/- 0.6 to 5.3 +/- 0.7mU/mg, p = .049), but did not change in HF-C (4.6 +/- 0.7 to 3.8 +/- 0.9mU/mg) following HFEE. We conclude that early skeletal muscle signaling responses to HFEE appear to be modified by dietary n-3PUFA content, but the potential impact on future development of metabolic disease needs exploring.