Simultaneous in vivo multi-organ fluxomics reveals divergent metabolic adaptations in liver, heart, and skeletal muscle during obesity.

ABSTRACT: We present an isotope-based metabolic flux analysis (MFA) approach to simultaneously quantify metabolic fluxes in the liver, heart, and skeletal muscle of individual mice. The platform was scaled to examine metabolic flux adaptations in age-matched cohorts of mice exhibiting varying levels of chronic obesity. We found that severe obesity increases hepatic gluconeogenesis and citric acid cycle flux, accompanied by elevated glucose oxidation in the heart that compensates for impaired fatty acid oxidation. In contrast, skeletal muscle fluxes exhibit an overall reduction in substrate oxidation. These findings demonstrate the dichotomy in fuel utilization between cardiac and skeletal muscle during worsening metabolic disease and demonstrate the divergent effects of obesity on metabolic fluxes i

SUBMITTER: Rahim M 

PROVIDER: S-EPMC12167616 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature