A high-fat high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle

K L Whytock, S A Parry, M C Turner, R M Woods, L J James, R A Ferguson, M Ståhlman, J Borén, J A Strauss, M Cocks, A J M Wagenmakers, C J Hulston, S O Shepherd

Research output: Contribution to journalArticle

Abstract

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. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)(In-press)
JournalJournal of Physiology
Volume(In-press)
Early online date20 Jan 2020
DOIs
Publication statusE-pub ahead of print - 20 Jan 2020
Externally publishedYes

Fingerprint

High Fat Diet
Skeletal Muscle
Triglycerides
Lipids
Insulin
Insulin Resistance
Perilipin-1
Diet
Glucose
Ceramides
Diglycerides
Quadriceps Muscle
Fats
Lipid Droplets
Biopsy
Muscles

Bibliographical note

This article is protected by copyright. All rights reserved.

Keywords

  • high-fat
  • intramuscular triglyceride
  • perilipin
  • confocal immunohistochemistry

Cite this

A high-fat high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle. / Whytock, K L; Parry, S A; Turner, M C; Woods, R M; James, L J; Ferguson, R A; Ståhlman, M; Borén, J; Strauss, J A; Cocks, M; Wagenmakers, A J M; Hulston, C J; Shepherd, S O.

In: Journal of Physiology, Vol. (In-press), 20.01.2020, p. (In-press).

Research output: Contribution to journalArticle

Whytock, KL, Parry, SA, Turner, MC, Woods, RM, James, LJ, Ferguson, RA, Ståhlman, M, Borén, J, Strauss, JA, Cocks, M, Wagenmakers, AJM, Hulston, CJ & Shepherd, SO 2020, 'A high-fat high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle' Journal of Physiology, vol. (In-press), pp. (In-press). https://doi.org/10.1113/JP279129
Whytock, K L ; Parry, S A ; Turner, M C ; Woods, R M ; James, L J ; Ferguson, R A ; Ståhlman, M ; Borén, J ; Strauss, J A ; Cocks, M ; Wagenmakers, A J M ; Hulston, C J ; Shepherd, S O. / A high-fat high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle. In: Journal of Physiology. 2020 ; Vol. (In-press). pp. (In-press).
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abstract = "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. This article is protected by copyright. All rights reserved.",
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T1 - A high-fat high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle

AU - Whytock, K L

AU - Parry, S A

AU - Turner, M C

AU - Woods, R M

AU - James, L J

AU - Ferguson, R A

AU - Ståhlman, M

AU - Borén, J

AU - Strauss, J A

AU - Cocks, M

AU - Wagenmakers, A J M

AU - Hulston, C J

AU - Shepherd, S O

N1 - This article is protected by copyright. All rights reserved.

PY - 2020/1/20

Y1 - 2020/1/20

N2 - 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. This article is protected by copyright. All rights reserved.

AB - 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. This article is protected by copyright. All rights reserved.

KW - high-fat

KW - intramuscular triglyceride

KW - perilipin

KW - confocal immunohistochemistry

U2 - 10.1113/JP279129

DO - 10.1113/JP279129

M3 - Article

VL - (In-press)

SP - (In-press)

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

ER -