Working Paper Article Version 1 This version is not peer-reviewed

Simulating Metabolic Flexibility in Low Energy Expenditure Conditions using Genome-scale Metabolic Models

Version 1 : Received: 21 May 2021 / Approved: 24 May 2021 / Online: 24 May 2021 (13:48:29 CEST)

A peer-reviewed article of this Preprint also exists.

Cabbia, A.; Hilbers, P.A.J.; van Riel, N.A.W. Simulating Metabolic Flexibility in Low Energy Expenditure Conditions Using Genome-Scale Metabolic Models. Metabolites 2021, 11, 695. Cabbia, A.; Hilbers, P.A.J.; van Riel, N.A.W. Simulating Metabolic Flexibility in Low Energy Expenditure Conditions Using Genome-Scale Metabolic Models. Metabolites 2021, 11, 695.

Abstract

Metabolic flexibility is the ability of an organism to adapt its energy source based on nutrient availability and energy requirements. In humans, this ability has been linked to cardio-metabolic health and healthy aging. Genome-scale metabolic models have been employed to simulate metabolic flexibility by computing the Respiratory Quotient (RQ), which is defined as the ratio of carbon dioxide produced to oxygen consumed, and varies between values of 0.7 for pure fat metabolism and 1.0 for pure carbohydrate metabolism. While the nutritional determinants of metabolic flexibility are known, the role of low energy expenditure and sedentary behavior in the development of metabolic inflexibility is less studied. In this study we present a new description of metabolic flexibility in genome-scale metabolic models which accounts for energy expenditure, and we study the interactions between physical activity and nutrition in a set of patient-derived models of skeletal muscle metabolism in older adults. The simulations show that fuel choice is sensitive to ATP consumption rate in all models tested. The ability to adapt fuel utilization to energy demands is an intrinsic property of the metabolic network

Keywords

metabolic flexibility, respiratory quotient, energy expenditure

Subject

Biology and Life Sciences, Biology and Biotechnology

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