Oxidation, Interconverting, Releasing, and Storage Flux of Circulating Nutrients in Lean and Obese Mice
Description
Abstract Mammalian tissues feed on nutrients in the blood circulation. At the organism-level, mammalian energy metabolism comprises of oxidation, storage, interconverting, and releasing of circulating nutrients. Though much is known about the individual processes and nutrients, a holistic and quantitative model describing these processes for all major circulating nutrients is lacking. Here, by integrating isotope tracer infusion, mass spectrometry, and isotope gas analyzer measurement, we developed a framework to systematically quantify fluxes through these metabolic processes for 10 major circulating energy nutrients in mice, resulting in an organism-level quantitative flux model of energy metabolism. This model revealed that in wildtype mice circulating nutrients have more dominant metabolic cycling fluxes than their oxidation fluxes, with distinct partition between cycling and oxidation flux for individual circulating nutrients. Applications of this framework in obese mouse models showed on a per animal or lean mass basis extensive elevation of metabolic cycling fluxes in ob/ob mice, but not in diet-induced obese mice. Thus, our framework describes quantitatively the functioning of energy metabolism at the organism-level, valuable for revealing new features of energy metabolism in physiological and disease conditions. Description of Files 1. "oxidation, interconverting, storage, and releasing flux.xlsx": This file details the oxidation, interconversion, release from storage, and futile storage flux of circulating nutrients on a per-animal basis. It includes data for lean C57BL/6J mice (control), obese C57BL/6J mice on a high-fat diet, and ob/ob obese mice. 2. "isotopologues.xlsx": This file presents the averaged carbon labeling in circulating nutrients at isotopic steady state under the infusion of various U-13C-tracers. The columns named as 0, 1, 2, 3, etc., indicate the number of atoms labeled as 13C in the analyte. More data is available in Data S1 – Source Data of the original publication in Cell Metabolism.
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Funding
Paul G. Allen Family Foundation
0034665
National Institutes of Health
R00DK117066
National Institutes of Health
R56DK140139