Project R-17012

Defining the potential of lactate and ketone bodies to potentiate exercise therapy in metabolic syndrome (Research)

Metabolic syndrome (MetS) affects ~30% of adults worldwide, imposing an enormous burden on both individual health and healthcare systems. Central to its pathophysiology are chronically elevated circulating free fatty acids (FFAs) and impaired mitochondrial function, which reinforce insulin resistance and metabolic inflexibility. Although exercise is the most potent intervention to target both defects, individuals with MetS exhibit blunted training adaptations and poor adherence, limiting its therapeutic impact. Interestingly, preliminary data from our group showed that elevating blood lactate and ketone bodies through ingestion of a novel lactate-ketone ester (LaKe) robustly suppresses circulating FFAs. Furthermore, we and others have shown that both metabolites independently improve glycaemic control and mitochondrial adaptations. This project will therefore investigate whether LaKe, by targeting the two central metabolic defects underlying MetS, can amplify the metabolic benefits of exercise in this population. Work package (WP) 1 will determine the acute effects of LaKe on circulating [FFA], glucose tolerance, and the serum lipidome at rest and during exercise. WP2 will assess whether 12-week LaKe supplementation during exercise training enhances insulin sensitivity, mitochondrial function, and the skeletal muscle lipidome compared to exercise alone. As such, this project will establish whether LaKe represents a viable adjunct to exercise therapy in individuals with MetS.

01 November 2026 - 31 October 2030