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The unfolded protein response in human skeletal muscle is not involved in the onset of glucose tolerance impairment induced by a fat-rich diet

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Abstract

Endoplasmic reticulum (ER) stress in pancreas, liver, and adipose tissue is a key event in the pathogenesis of obesity-related metabolic disease. Lipid-induced ER stress in liver and adipose tissue leads to inhibition of insulin signaling. Whether this mechanism exists in skeletal muscle is currently unknown. The present study aimed at assessing the ER stress response in skeletal muscle of subjects receiving a hyper-caloric fat-rich diet (HFD). Seven healthy males (20.6 ± 0.5 years; 70.9 ± 3.4 kg) volunteered to participate in the study. They received a hyper-caloric (+30% kcal) fat-rich (50% kcal) diet for 6 weeks. An oral glucose tolerance test (OGTT) was performed, and muscle biopsies were taken before and after HFD. HFD increased body mass by ~3 kg (P = 0.007) and the sum of skinfolds by 15% (P = 0.003). After HFD, blood glucose concentrations were higher during OGTT (two-way ANOVA, P = 0.023; +45% at 20 min, P = 0.002), and fasting plasma insulin level tended to be higher (+20%). HFD increased intramyocellular lipids content by ~50 and 75% in type I (P = 0.0009) and IIa fibers (P = 0.002), respectively. The protein expression of inositol-requiring enzyme 1α, protein kinase R-like ER protein kinase, BiP and calnexin and the mRNA level of spliced X box binding protein-1, CCAAT/enhancer binding protein homologous protein and activating transcription factor 4 were not changed after HFD. Despite the increase in body mass, subcutaneous fat deposits, and intramyocellular lipids content, ER stress markers were unchanged in skeletal muscle of subjects receiving a HFD for 6 weeks. This suggests that the onset of glucose intolerance is not related to ER stress in skeletal muscle.

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Acknowledgments

The authors thank Paul Van Veldhoven, Department Molecular Celbiology, LIPIT, K.U. Leuven, for researching data. The authors would also like to thank Raf Van Dyck, Research Centre for Exercise and Health, Department of Biomedical Kinesiology, K.U. Leuven for the assistance with the dietary analyses and Monique Ramaekers, Research Centre for Exercise and Health, Department of Biomedical Kinesiology, K.U. Leuven, for assistance during the oral glucose tolerance tests. LD has postdoctoral fellowship from the Fonds National de la Recherche Scientifique (Belgium). This study was granted by the Fonds de la Recherche Scientifique Médicale (FRSM 3.4514.) and by the Fonds Spéciaux de Recherche from the Université catholique de Louvain. This study was also supported by grant OT/05/53 from the Katholieke Universiteit Leuven and grant G.0233.05 F from the Fund for Scientific Research-Flanders, Belgium (F.W.O.-Vlaanderen).

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Correspondence to Marc Francaux.

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Communicated by Håkan Westerblad.

L. Deldicque and K. Van Proeyen contributed equally as first authors.

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Deldicque, L., Van Proeyen, K., Francaux, M. et al. The unfolded protein response in human skeletal muscle is not involved in the onset of glucose tolerance impairment induced by a fat-rich diet. Eur J Appl Physiol 111, 1553–1558 (2011). https://doi.org/10.1007/s00421-010-1783-1

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  • DOI: https://doi.org/10.1007/s00421-010-1783-1

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