Implication of lipid turnover for the control of energy balance

The ongoing obesity epidemic is a consequence of a progressive energy imbalance. The energy-balance model (EBM) posits that obesity results from an excess in food intake and circulating fuels. A reversal in causality has been proposed recently in the form of the carbohydrate-insulin model (CIM), according to which fat storage drives energy imbalance. Under the CIM, dietary carbohydrates shift energy use in favour of storage in adipose tissue. The dynamics of lipid storage and mobilization could, therefore, be sensitive to changes in carbohydrate intake and represent a measurable component of the CIM. To characterize potential changes in lipid dynamics induced by carbohydrates, mathematical models were used. Here, we propose a coherent mathematical implementation of the CIM-energy deposition model (CIM-EDM), which includes lipid turnover dynamics. Using lipid turnover data previously obtained by radiocarbon dating, we build two cohorts of virtual patients and simulate lipid dynamics during ageing and weight loss. We identify clinically testable lipid dynamic parameters that discriminate between the CIM-EDM and an energy in, energy out implementation of the EBM (EBM-IOM). Using a clinically relevant two-month virtual trial, we additionally identify scenarios and propose mechanisms whereby individuals may respond differently to low-carbohydrate diets. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.