Substrate fluxes in brown adipocytes upon adrenergic stimulation and uncoupling protein 1 ablation.
Substrate fluxes in brown adipocytes upon adrenergic stimulation and uncoupling protein 1 ablation.
复制标题
DOI：
10.26508/lsa.201800136
复制
发表时间：
2018-12
影响因子：
4.4
通讯作者：
Fromme T
中科院分区：
文献类型：
--
作者：
Schweizer S;Oeckl J;Klingenspor M;Fromme T
棕色脂肪细胞中底物通量的定量阐明了细胞外酸化的贡献者，确定了脂解和再酯化的无效循环，并表明了糖原在活化过程中的作用。棕色脂肪细胞是高度特化的细胞，具有独特的代谢能力，以热量的形式耗散化学能。我们确定并推断了一些关键的分解代谢产物的通量，它们对肾上腺素能刺激的反应变化，以及对产热解偶联蛋白1和/或氧化磷酸化存在的依赖性。这项研究提供了参考值，以近似通量率从一组有限的测量参数，在未来，从而允许评估的可信度的要求代谢适应或操纵的能力。从所得模型中，我们描绘了在棕色脂肪细胞中（1）游离脂肪酸是细胞外酸化的重要贡献者，（2）糖原是对肾上腺素能刺激的急性反应中的主要糖酵解底物来源，以及（3）游离脂肪酸在脂解和再酯化成甘油三酯之间的无效循环提供了解偶联蛋白1-独立的机制，棕色脂肪细胞中的非颤抖性产热。
Quantification of substrate fluxes in brown adipocytes clarifies contributors to extracellular acidification, identifies a futile cycle of lipolysis and re-esterification, and suggests a role for glycogen during activation. 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.