Dysregulation of early gene response to a mixed meal in skeletal muscle in obesity and type 2 diabetes

Makhnovskii, P.A.; Lednev, E.M.; Gavrilova, A.O.; Kurochkina, N.S.; Vepkhvadze, T.F.; Shestakova, M.V.; Popov, D.V.

Авторы: Makhnovskii Pavel A., Lednev Egor M., Gavrilova Alina O., Kurochkina Nadia S., Vepkhvadze Tatiana F., Shestakova Marina V., Popov Daniil V.
Журнал: Physiological Genomics
Том: 55
Номер: 10
Год издания: 2023
Издательство: American Physiological Society
Местоположение издательства: United States
Первая страница: 468
Последняя страница: 477
DOI: 10.1152/physiolgenomics.00046.2023
Аннотация: Obesity- and type 2 diabetes mellitus-induced changes in the expression of protein-coding genes in human skeletal muscle were extensively examined at baseline (after an overnight fast). We aimed to compare the early transcriptomic response to a typical single meal in skeletal muscle of metabolically healthy subjects and obese individuals without and with type 2 diabetes. Transcriptomic response (RNA-seq) to a mixed meal (nutritional drink, ∼25 kJ/kg of body mass) was examined in the vastus lateralis muscle (1 h after a meal) in 7 healthy subjects and 14 obese individuals without or with type 2 diabetes. In all obese individuals, the transcriptome response to a meal was dysregulated (suppressed and altered) and associated with different biological processes compared with healthy control. To search for potential transcription factors regulating transcriptomic response to a meal, the enrichment of transcription factor-binding sites in individual promoters of the human skeletal muscle was examined. In obese individuals, the transcriptomic response is associated with a different set of transcription factors than that in healthy subjects. In conclusion, metabolic disorders are associated with a defect in the regulation of mixed meal/insulin-mediated gene expression-insulin resistance in terms of gene expression. Importantly, this dysregulation occurs in obese individuals without type 2 diabetes, i.e., at the first stage of the development of metabolic disorders.
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Dysregulation of early gene response to a mixed meal in skeletal muscle in obesity and type 2 diabetesстатья

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