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A 7‐day high‐fat, high‐calorie diet induces fibre‐specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle

journal contribution
posted on 25.02.2020 by KL Whytock, SA Parry, MC Turner, Rachel Woods, Lewis James, Richard Ferguson, M Ståhlman, J Borén, JA Strauss, M Cocks, AJM Wagenmakers, Carl Hulston, SO Shepherd
KEY POINTS: We have recently shown that a high-fat high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days HFHC diet on: 1) skeletal muscle concentration of lipid metabolites, and 2) potential changes in the perilipin (PLIN) content of the lipid droplets (LD) storing IMTG. The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to LD stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance. ABSTRACT: A HFHC diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LD) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LD has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (n = 11 males, n = 2 females) healthy lean individuals (age: 23 ± 2.5 y, BMI: 24.5 ± 2.4 kg m-2 ), following an overnight fast, before and after consuming a high-fat (64% energy) high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+10%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (80%; P < 0.01), also in type I fibres only. We propose that these adaptations to LD support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days HFHC diet.

Funding

National Institute for Health Research (NIHR) Leicester Biomedical Research Centre

History

School

  • Sport, Exercise and Health Sciences

Published in

The Journal of Physiology

Volume

598

Issue

6

Pages

1151-1167

Publisher

Wiley

Version

AM (Accepted Manuscript)

Rights holder

© The Authors. The Journal of Physiology. The Physiological Society.

Publisher statement

This is the peer reviewed version of the following article: WHYTOCK, K.L. ... et al., 2020. A 7‐day high‐fat, high‐calorie diet induces fibre‐specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle. The Journal of Physiology, 598(6), pp. 1151-1167, which has been published in final form at https://doi.org/10.1113/JP279129. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Acceptance date

13/01/2020

Publication date

2020-01-20

Copyright date

2020

ISSN

0022-3751

eISSN

1469-7793

Language

en

Depositor

Dr Carl Hulston. Deposit date: 21 February 2020

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