Human skeletal muscle metabolic responses to 6 days of high‐fat overfeeding are associated with dietary n‐3PUFA content and muscle oxidative capacity. Issue 16 (26th August 2020)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Physiological reports. Volume 8:Issue 16(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-26
• Subjects: exercise -- fish oil -- insulin resistance -- omega‐3 -- overfeeding -- type 2 diabetes; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.14529
• Languages: English
• ISSNs: 2051-817X

Abstract

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. Abstract : High‐fat high‐energy diets contribute to development of insulin resistance and type 2 diabetes, and n‐3PUFA have been proposed to improve insulin sensitivity. We examined the potential for dietary n‐3PUFA to mitigate negative metabolic consequences of short‐term high‐fat overfeeding in healthy adult males. We report that short‐term high‐fat energy excess over 6 d did not lead to whole body changes in glucose handling, but changes at the cellular level did occur, including an increase in muscle ceramide species. We show that substituting 10% of total fats for n‐3PUFA during a short term high‐fat high‐energy diet appears to lead to early differential modifications in cellular signalling responses linked to metabolic health outcomes, but these findings require replication and further study.