Pyruvate dehydrogenase complex plays a central role in brown adipocyte energy expenditure and fuel utilization during short-term beta-adrenergic activation.
Pyruvate dehydrogenase complex plays a central role in brown adipocyte energy expenditure and fuel utilization during short-term beta-adrenergic activation.
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DOI：
10.1038/s41598-018-27875-3
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发表时间：
2018-06-22
影响因子：
4.6
通讯作者：
Houtkooper RH
中科院分区：
文献类型：
--
作者：
Held NM;Kuipers EN;van Weeghel M;van Klinken JB;Denis SW;Lombès M;Wanders RJ;Vaz FM;Rensen PCN;Verhoeven AJ;Boon MR;Houtkooper RH
棕色脂肪组织（BAT）的激活有助于通过能量耗散为热量的总身体能量消耗。活化的BAT增加脂质和葡萄糖从循环中的清除，但BAT如何适应多种底物的大量流入尚不清楚。为研究β3-肾上腺素能受体（β3-AR）激活对棕色脂肪细胞代谢的影响，采用Seahorse呼吸测定法，在β3-AR激动剂CL 316，243存在或不存在的情况下，将T37 i小鼠前脂肪细胞诱导分化为棕色脂肪细胞。这些棕色脂肪细胞使用的主要底物是脂肪酸，其在活化过程中以及在静息状态下被同等地氧化。基于[U-13 C]-葡萄糖示踪剂的代谢组学研究表明，通过TCA循环的通量受到丙酮酸脱氢酶（PDH）活性的增强和调节。基于脂质中的13 C-示踪剂掺入，似乎大多数葡萄糖通过TCA循环活性被氧化，而一些葡萄糖用于甘油-3-磷酸合成以补充甘油三酯库。总的来说，我们表明，虽然脂肪酸是氧化的主要底物，但葡萄糖也被氧化，以满足短期β3-AR激活期间增加的能量需求。PDH在指导葡萄糖碳氧化中起重要作用。
Activation of brown adipose tissue (BAT) contributes to total body energy expenditure through energy dissipation as heat. Activated BAT increases the clearance of lipids and glucose from the circulation, but how BAT accommodates large influx of multiple substrates is not well defined. The purpose of this work was to assess the metabolic fluxes in brown adipocytes during β3-adrenergic receptor (β3-AR) activation.T37i murine preadipocytes were differentiated into brown adipocytes and we used Seahorse respirometry employing a set of specific substrate inhibitors in the presence or absence of β3-AR agonist CL316,243. The main substrate used by these brown adipocytes were fatty acids, which were oxidized equally during activation as well as during resting condition. [U-13C]-glucose tracer-based metabolomics revealed that the flux through the TCA cycle was enhanced and regulated by pyruvate dehydrogenase (PDH) activity. Based on 13C-tracer incorporation in lipids, it appeared that most glucose was oxidized via TCA cycle activity, while some was utilized for glycerol-3-phosphate synthesis to replenish the triglyceride pool. Collectively, we show that while fatty acids are the main substrates for oxidation, glucose is also oxidized to meet the increased energy demand during short term β3-AR activation. PDH plays an important role in directing glucose carbons towards oxidation.
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DOI：
10.1016/j.tem.2017.01.004
发表时间：
2017-05
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Lee PL;Jung SM;Guertin DA
通讯作者：
Guertin DA
影响因子：
16.6
作者：
Berbée JF;Boon MR;Khedoe PP;Bartelt A;Schlein C;Worthmann A;Kooijman S;Hoeke G;Mol IM;John C;Jung C;Vazirpanah N;Brouwers LP;Gordts PL;Esko JD;Hiemstra PS;Havekes LM;Scheja L;Heeren J;Rensen PC
通讯作者：
Rensen PC
影响因子：
2.3
作者：
Fernandez-Fernandez, Mario;Rodriguez-Gonzalez, Pablo;Garcia Alonso, J. Ignacio
通讯作者：
Garcia Alonso, J. Ignacio
影响因子：
7.7
作者：
Hanssen, Mark J. W.;van der Lans, Anouk A. J. J.;Lichtenbelt, Wouter D. van Marken
通讯作者：
Lichtenbelt, Wouter D. van Marken
影响因子：
56.9
作者：
Haemmerle, G;Lass, A;Zechner, R
通讯作者：
Zechner, R