期刊
ACTA DIABETOLOGICA
卷 57, 期 7, 页码 819-826出版社
SPRINGER-VERLAG ITALIA SRL
DOI: 10.1007/s00592-020-01490-z
关键词
Unfolded protein response; Skeletal muscle; Obesity; Glucose intolerance; Bariatric surgery
资金
- Lille University-Region Hauts-de-France
- EGID funds
- INSERM
- Contrat Plan Etat Region (CPER)
- Region Hauts-de-France/FEDER
- CTRLLille Pasteur Institute
- European Genomic Institute for Diabetes (E.G.I.D.) [ANR-10-LABX-46]
- European Foundation for the Study of Diabetes (EFSD)
- Fondation Francophone pour la Recherche sur le Diabete (FFRD) - Federation Francaise des Diabetiques (AFD)
- AstraZeneca
- Eli Lilly
- Merck Sharp Dohme (MSD)
- Novo Nordisk
- Sanofi
- Advanced ERC Grant [694717]
- European Research Council (ERC) [694717] Funding Source: European Research Council (ERC)
Aims Not all people with obesity become glucose intolerant, suggesting differential activation of cellular pathways. The unfolded protein response (UPR) may contribute to the development of insulin resistance in several organs, but its role in skeletal muscle remains debated. Therefore, we explored the UPR activation in muscle from non-diabetic glucose tolerant or intolerant patients with obesity and the impact of bariatric procedures. Methods Muscle biopsies from 22 normoglycemic (NG, blood glucose measured 120 min after an oral glucose tolerance test, G120 < 7.8 mM) and 22 glucose intolerant (GI, G120 between 7.8 and 11.1 mM) patients with obesity were used to measure UPR activation by RTqPCR and western blot. Then, UPR was studied in biopsies from 7 NG and 7 GI patients before and 1 year after bariatric surgery. Results Binding immunoglobulin protein (BIP) protein was similar to 40% higher in the GI compared to NG subjects. Contrastingly, expression of the UPR-related genes BIP, activating transcription factor 6 (ATF6) and unspliced X-box binding protein 1 (XBP1u) were significantly lower and C/EBP homologous protein (CHOP) tended to decrease (p = 0.08) in GI individuals. While BIP protein positively correlated with fasting blood glucose (r = 0.38, p = 0.01), ATF6 and CHOP were associated with G120 (r = - 0.38 and r = - 0.41, p < 0.05) and the Matsuda index (r = 0.37 and r = 0.38, p < 0.05). Bariatric surgery improved metabolic parameters, associated with higher CHOP expression in GI patients, while ATF6 tended to increase (p = 0.08). Conclusions CHOP and ATF6 expression decreased in non-diabetic GI patients with obesity and was modified by bariatric surgery. These genes may contribute to glucose homeostasis in human skeletal muscle.
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