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

Wardle, Sophie L.; Macnaughton, Lindsay S.; McGlory, Chris; Witard, Oliver C.; Dick, James R.; Whitfield, Philip D.; Ferrando, Arny A.; Wolfe, Robert R; Kim, Il-Young; Hamilton, D. Lee; Moran, Colin N.; Tipton, Kevin D.; Galloway, Stuart D.R.

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 AMPKα2 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 AMPKα2 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.

Citation

Wardle, S. L., Macnaughton, L. S., McGlory, C., Witard, O. C., Dick, J. R., Whitfield, P. D., Ferrando, A. A., Wolfe, R. R., Kim, I.-Y., Hamilton, D. L., Moran, C. N., Tipton, K. D., & Galloway, S. D. (2020). Human skeletal muscle metabolic responses to 6 days of high‐fat overfeeding are associated with dietary n‐3PUFA content and muscle oxidative capacity. Physiological Reports, 8(16), Article e14529. https://doi.org/10.14814/phy2.14529

• Journal Article Type: Article
• Acceptance Date: Jul 10, 2020
• Online Publication Date: Aug 26, 2020
• Publication Date: 2020-08
• Deposit Date: Aug 27, 2020
• Publicly Available Date: Aug 27, 2020
• Journal: Physiological Reports
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 16
• Article Number: e14529
• DOI: https://doi.org/10.14814/phy2.14529
• Public URL: https://durham-repository.worktribe.com/output/1293947