title: The unfolded protein response in human skeletal muscle is not involved in the onset of glucose tolerance impairment induced by a fat-rich diet.
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.
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, 1, Place Pierre de Coubertin, 1348 Louvain-la-Neuve, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
authors.forename: Karen
authors.initials: K
authors.lastname: Van Proeyen
authors.forename: Marc
authors.initials: M
authors.lastname: Francaux
authors.forename: Peter
authors.initials: P
authors.lastname: Hespel
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D056811:Unfolded Protein Response / Q000187:drug effects / Q000502:physiology*; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D008055:Lipids