Systems biology reveals uncoupling beyond UCP1 in human white fat-derived beige adipocytes

Schematic representation of the framework for evaluation of mechanisms of proton leak in human beige adipocytes. a Commonly measured variables like UCP1 mRNA levels are insufficient to properly characterize the bioenergetics system. We show that measurements of UCP1 protein levels and functional responses are required, and mathematical modeling is important to correctly integrate and interpret the data. b Hypothesis testing with mathematical modeling is an iterative approach used to reject implausible explanations and thereby advance the understanding. Herein, we have used hypothesis testing to unravel an increased uncoupled respiration in BMP4-treated cells. UCP1 uncoupling protein 1, ETC electron transport chain, BMP4 bone morphogenic protein