The analysis of the skeletal muscle metabolism is crucial for designing optimal exercise paradigms in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted...

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Published in:	Molecular medicine (Cambridge, Mass.) Vol. 30; no. 1; pp. 80 - 16
Main Authors:	Abi Akar, Elias, Weill, Laure, El Khoury, Mirella, Caradeuc, Cédric, Bertho, Gildas, Boutary, Suzan, Bezier, Cynthia, Clerc, Zoé, Sapaly, Delphine, Bendris, Sabrina, Cheguillaume, Flore, Giraud, Nicolas, Eid, Assaad A, Charbonnier, Frédéric, Biondi, Olivier
Format:	Journal Article
Language:	English
Published:	England BioMed Central 10-06-2024 BMC
Subjects:	Animals Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - therapy Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - therapy Diet, High-Fat - adverse effects Disease Models, Animal Female Insulin Resistance Male Metabolome Metabolomics - methods Mice Mice, Inbred C57BL Mice, Transgenic Mouse models Muscle metabolism Muscle, Skeletal - metabolism Physical Conditioning, Animal Precision exercise Type 2 diabetes mellitus Precision exercise Type 2 diabetes mellitus Mouse models Muscle metabolism
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Summary:	Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription of personalized exercise programs specifically designed to reverse the potential metabolic alterations in skeletal muscle could result in better results. To test this hypothesis, we drew the metabolic signature of the fast-twitch quadriceps muscle, based on a combined unbiased NMR spectroscopy and RT-qPCR study, in several T2DM mouse models of different genetic background (129S1/SvImJ, C57Bl/6J), sex and aetiology (high-fat diet (HFD) or HFD/Streptozotocin (STZ) induction or transgenic MKR (FVB-Tg Ckm-IGF1R*K1003R)1Dlr/J) mice. Three selected mouse models with unique muscular metabolic signatures were submitted to three different swimming-based programs, designed to address each metabolic specificity. We found that depending on the genetic background, the sex, and the mode of T2DM induction, specific muscular adaptations occurred, including depressed glycolysis associated with elevated PDK4 expression, shift to β-oxidation, or deregulation of amino-acid homeostasis. Interestingly, dedicated swimming-based exercises designed to restore specific metabolic alterations in muscle were found optimal in improving systemic T2DM hallmarks, including a significant reduction in insulin resistance, the improvement of glucose homeostasis, and a delay in sensorimotor function alterations. The muscle metabolism constitutes an important clue for the design of precision exercises with potential clinical implications for T2DM patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1528-3658 1076-1551 1528-3658
DOI:	10.1186/s10020-024-00850-7