Role of Elevated Lactate Levels on Lipid and Carbohydrate Metabolism.

Role of Elevated Lactate Levels on Lipid and Carbohydrate Metabolism.

The purpose of this study is to investigate whether the elevated circulating lactate levels of individuals with metabolic syndrome are responsible for their reduced lipolysis and glucose tolerance. The investigators will conduct an intervention study in which blood lactate levels will be elevated via intravenous infusion of sodium lactate. State of the art metabolic assessment using stable isotopes and indirect calorimetry will be used to study alterations in fat and carbohydrate metabolism.

Individuals with metabolic syndrome and insulin resistance exhibit higher resting lactate concentrations than age-matched counterparts without metabolic disease. Recent studies suggest that lactate is not just a by-product of accelerated glycolysis but a signaling molecule that could even affect gene expression. However, the role of lactate in carbohydrate and fat metabolism at rest and during exercise remains incompletely described.

In this study, the investigators will elevate blood lactate levels in metabolically healthy individuals to levels observed in individuals with metabolic syndrome while measuring fat and carbohydrate metabolism in a fasted state, during exercise, and in response to an oral glucose load (oral glucose tolerance test).

10 metabolically healthy (MH) and 10 metabolically impaired (MI) individuals matched for sex and physical activity will participate in the study. MH will undergo two trials: one with intravenous lactate infusion and the other with isovolumetric saline infusion. The MI group will undergo only the saline trial.

Each trial consists of a 150 min basal period, an exercise period, followed by a 2-hour oral glucose tolerance test (OGTT). During the test, the investigators will:

Measure insulin sensitivity during the OGTT (Matsuda Index). Measure fat and carbohydrate oxidation using indirect calorimetry. Use stable isotope infusion to measure glycerol and glucose turnover rates in plasma using [1,1,2,3,3 2H]-glycerol and [6-6 2H], [U, 13C] - glucose.

Collect blood samples of relevant hormones, metabolites, and cytokines.

Inclusion Criteria:

• Men and women
• >18 years of age
• Women non-pregnant or taking contraceptive medication
• Physically active according to WHO's guidelines
• Metabolic syndrome as IDF 2009 criteria (Alberti et al., Circulation)
• Written and verbal consent to participation

Exclusion Criteria:

• Chronic illness that prevents them from exercising
• Affected blood samples at screening, as assessed by the PI
• Assessed as unsuitable by PI