Introduction and Objective: Altered carbohydrate or lipid metabolism are characteristic of metabolic dysfunction in obesity. Bariatric surgery is an effective treatment for obesity that induces rapid remission of metabolic dysfunction, suggesting early reprogramming. Skeletal muscle (Skm) is a major contributor to whole body metabolism; thus it is a critical tissue for understanding these changes. However, the outcomes of surgery on resolving perturbations in whole-body and Skm substrate metabolism are underexplored. To identify systemic and Skm metabolic changes following bariatric surgery that may underly resolution of metabolic dysfunction.Methods: Sedentary females (N=9), aged 38.2±7.7yrs, with severe obesity (BMI 46.1±3.7kg/m2), were examined 0-8 weeks before and 4-6 weeks after bariatric surgery. A Skm biopsy from the vastus lateralis was used to isolate primary human skeletal muscle stem cells (HSkMCs) and blood taken at each fasted visit. Whole-body substrate oxidation was assessed via indirect calorimetry. Intrinsic substrate oxidation from HSkMCs was analyzed using 14C labeled glucose, oleate, and palmitate.Results: We observed a significant decrease in whole-body respiratory quotient (-8.9±7.1%, p=0.04) and fasting insulin (-52.2±19.6%, p=0.002), whereas free fatty acids (30.1±28.7%, p=0.03) and beta-hydroxybutyrate levels increased post-surgery (684.4±838.8%, p=0.005). Surgery did not induce any alterations in HSkMCs substrate oxidation.Conclusion: These observations indicate an early shift to greater lipid utilization at the whole-body level following surgery, evidenced by reduced carbohydrate oxidation and increased circulating lipid derived substrates. In contrast, HSkMC substrate metabolism displayed no altered preferences, suggesting a metabolic reprogramming driven by systemic factors potentially contributing to other tissue changes, rather than intrinsic changes in HSkMC.
G. Tiralla: None. D. Zheng: None. C.J. Tanner: None. M. Chumakova-Orin: None. W.J. Pories: None. L. Dohm: None. J.A. Houmard: None. N.T. Broskey: None.
R01DK120296R01DK137945
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