Substrate Utilization by Brown Adipose Tissue: What's Hot and What's Not?
Substrate Utilization by Brown Adipose Tissue: What's Hot and What's Not?
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DOI：
10.3389/fendo.2020.571659
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发表时间：
2020
影响因子：
5.2
通讯作者：
Stimson RH
中科院分区：
文献类型：
--
作者：
McNeill BT;Morton NM;Stimson RH
在过去的10年里，我们对人类棕色脂肪组织（BAT）功能的了解迅速增加。这主要是由于强大的非侵入性成像技术的发展，如正电子发射断层扫描，可以使用代谢示踪剂量化BAT的质量和功能。在冷诱导产热过程中BAT的激活是耗散能量以产生热量的有效方式，并且需要利用多种能量底物以实现最佳功能。这引起了人们对激活BAT作为2型糖尿病、血脂异常和肥胖症的潜在治疗靶点的兴趣。在这里，我们提供了一个概述，目前的理解BAT底物利用在人类中，并强调在啮齿动物中发现的其他机制，其中BAT更显着地有助于能量消耗。在产热过程中，BAT表现出显著增加的葡萄糖摄取，这似乎对BAT功能至关重要。然而，葡萄糖没有被完全氧化，大部分转化为乳酸盐。产热的主要能量底物是脂肪酸，从棕色脂肪细胞甘油三酯储存中释放出来。活性BAT还隔离循环脂质以维持最佳产热。最近的证据表明，来自三羧酸循环和糖酵解途径的代谢中间体也在BAT功能中发挥关键作用。了解这些代谢物在调节产热和全身底物利用中的作用可能会阐明治疗BAT激活的新策略。
Our understanding of brown adipose tissue (BAT) function in humans has increased rapidly over the past 10 years. This is predominantly due to the development of powerful non-invasive imaging techniques such as positron emission tomography that can quantify BAT mass and function using metabolic tracers. Activation of BAT during cold–induced thermogenesis is an effective way to dissipate energy to generate heat and requires utilization of multiple energy substrates for optimal function. This has led to interest in the activation of BAT as a potential therapeutic target for type 2 diabetes, dyslipidaemia, and obesity. Here, we provide an overview of the current understanding of BAT substrate utilization in humans and highlight additional mechanisms found in rodents, where BAT more prominently contributes to energy expenditure. During thermogenesis, BAT demonstrates substantially increased glucose uptake which appears to be critical for BAT function. However, glucose is not fully oxidized, with a large proportion converted to lactate. The primary energy substrate for thermogenesis is fatty acids, released from brown adipocyte triglyceride stores. Active BAT also sequesters circulating lipids to sustain optimal thermogenesis. Recent evidence reveals that metabolic intermediates from the tricarboxylic acid cycle and glycolytic pathways also play a critical role in BAT function. Understanding the role of these metabolites in regulating thermogenesis and whole body substrate utilization may elucidate novel strategies for therapeutic BAT activation.
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影响因子：
4.6
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
通讯作者：
Houtkooper RH
影响因子：
4.6
作者：
Jeong JH;Chang JS;Jo YH
通讯作者：
Jo YH
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：
64.5
作者：
Fedorenko A;Lishko PV;Kirichok Y
通讯作者：
Kirichok Y
影响因子：
5.8
作者：
Iwen, K. Alexander;Backhaus, Jenny;Schmid, Sebastian M.
通讯作者：
Schmid, Sebastian M.