227-LB: Elevated Plasma Lactate and the Risk for Metabolic Syndrome—Is Skeletal Muscle a Producer or Consumer?

Autor: NICHOLAS T. BROSKEY, TERRY E. JONES, CHUCK J. TANNER, DONGHAI ZHENG, FILIP JEVTOVIC, POLINA KRASSOVSKAIA, LAURA E. MATARESE, RONALD N. CORTRIGHT, ROBERT HICKNER, ERIC J. DEMARIA, WALTER J. PORIES, JOSEPH A. HOUMARD, LYNIS DOHM
Rok vydání: 2022
Předmět:
Zdroj: Diabetes. 71
ISSN: 0012-1797
Popis: Background: The incidence of metabolic diseases is rising and there is a dire need for early detection to implement prevention. Fasting plasma lactate concentrations have been shown to be elevated in individuals with obesity and predictive of type 2 diabetes. An elevated fasting lactate concentration could possibly be the product of a reduction in muscle oxidative capacity and increased muscle lactate output. However, it is unknown how early this is evident, as are the mechanisms involved. Aim: The aim of this study was to determine if fasting lactate concentrations were linked with a reduction in skeletal muscle oxidative capacity in a cohort without metabolic disease. Methods: Young (age 28 ± 7; N=21) overweight (BMI (27.1 ± 0.4 kg/m2) men (n=12) and women (n=9) were recruited for this study. Blood biomarkers were measured in the fasted state and body composition was determined by DXA. Muscle oxidative capacity was measured in skeletal muscle homogenates (vastus lateralis biopsy) using 14C-labeled labeled palmitate and pyruvate. Muscle lactate output was determined by microdialysis during a hyperinsulinemic euglycemic clamp procedure. Results: Elevated lactate was associated with elevated visceral adiposity (R2=.40, p=.003) , elevated triglycerides (R2=.56, p=.0001) , as well as elevations in systolic blood pressure (R2=.39, p=.003) . Subjects with higher lactate had lower ratio of fatty acid oxidation to pyruvate oxidation (ratio R2=.49, p=.002) . Muscle lactate uptake in the basal state of the clamp positively associated with plasma lactate (R2=.92, p= Conclusion: Individuals who are overweight but otherwise healthy have elevated plasma lactate that associates with parameters of the metabolic syndrome. Lactate was associated with a shift from lipid to carbohydrate oxidation. Muscle is a consumer of lactate in the fasted state, whereas adipose tissue may be the source of production postprandially. Disclosure N. T. Broskey: None. E. J. Demaria: None. W. J. Pories: None. J. A. Houmard: None. L. Dohm: None. T. E. Jones: None. C. J. Tanner: None. D. Zheng: None. F. Jevtovic: None. P. Krassovskaia: None. L. E. Matarese: None. R. N. Cortright: None. R. Hickner: None. Funding NIH (R01DK120296)
Databáze: OpenAIRE