Work

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

Year: 2025

Type: article

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 in different organs. This multi-tissue MFA technology can be extended to address important questions about in vivo regulation of metabolism and its dysregulation in disease, which cannot be fully answered through studies of single organs or isolated cells/tissues.

Source: Cell Reports

DOI: 10.1016/j.celrep.2025.115591

Authors: Mohsin Rahim, Tomasz K. Bednarski, Clinton M. Hasenour, Deveena R. Banerjee, Irina Trenary, Jamey D. Young

Institution: Vanderbilt University

Language: English

Topic: Metabolomics and Mass Spectrometry Studies

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620