PT  - JOURNAL ARTICLE
AU  - Sabine Schweizer
AU  - Josef Oeckl
AU  - Martin Klingenspor
AU  - Tobias Fromme
TI  - Substrate fluxes in brown adipocytes upon adrenergic stimulation and uncoupling protein 1 ablation
AID  - 10.26508/lsa.201800136
DP  - 2018 Dec 01
TA  - Life Science Alliance
PG  - e201800136
VI  - 1
IP  - 6
4099  - https://www.life-science-alliance.org/content/1/6/e201800136.short
4100  - https://www.life-science-alliance.org/content/1/6/e201800136.full
SO  - Life Sci. Alliance2018 Dec 01; 1
AB  - 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.