TY - JOUR T1 - Substrate fluxes in brown adipocytes upon adrenergic stimulation and uncoupling protein 1 ablation JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800136 VL - 1 IS - 6 SP - e201800136 AU - Sabine Schweizer AU - Josef Oeckl AU - Martin Klingenspor AU - Tobias Fromme Y1 - 2018/12/01 UR - https://www.life-science-alliance.org/content/1/6/e201800136.abstract N2 - Brown adipocytes are highly specialized cells with the unique metabolic ability to dissipate chemical energy in the form of heat. We determined and inferred the flux of a number of key catabolic metabolites, their changes in response to adrenergic stimulation, and the dependency on the presence of the thermogenic uncoupling protein 1 and/or oxidative phosphorylation. This study provides reference values to approximate flux rates from a limited set of measured parameters in the future and thereby allows to evaluate the plausibility of claims about the capacity of metabolic adaptations or manipulations. From the resulting model, we delineate that in brown adipocytes (1) free fatty acids are a significant contributor to extracellular acidification, (2) glycogen is the dominant glycolytic substrate source in the acute response to an adrenergic stimulus, and (3) the futile cycling of free fatty acids between lipolysis and re-esterification into triglyceride provides a mechanism for uncoupling protein 1–independent, non-shivering thermogenesis in brown adipocytes. ER -