Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel-dependent mechanisms
Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel-dependent mechanisms
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DOI：
10.1111/bph.13514
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发表时间：
2016-08-01
影响因子：
7.3
通讯作者：
Thyagarajan, Baskaran
中科院分区：
文献类型：
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作者：
Baskaran, Padmamalini;Krishnan, Vivek;Thyagarajan, Baskaran
背景和目的肥胖和代谢性疾病的流行日益严重，需要开发新的策略来预防和治疗这些疾病。目前的研究表明，白色脂肪组织的褐化(WAT)促进了能量消耗，以对抗肥胖。最近的研究表明，激活TRPV1通道可以对抗肥胖。然而，激活TRPV1通道对抗肥胖的机制仍不清楚。实验方法我们利用野生型和TRPV1(-/-)小鼠模型，通过激活TRPV1通道来评估饮食辣椒素诱导WAT褐化程序的效果。我们利用这些小鼠的前脂肪细胞和脂肪垫进行了实验。关键结果辣椒素刺激WAT中棕色脂肪特异的生热解偶联蛋白-1和骨形态发生蛋白-8b的表达。辣椒素通过TRPV1通道依赖性的细胞内钙升高和钙/钙调素激活的蛋白激酶II和AMP激活的蛋白激酶II的磷酸化，促进sirtuin-1的表达和活性，从而触发Wat褐变。辣椒素可增加PPAR 1辅活化子的表达，增强代谢和活动能力。此外，辣椒素刺激依赖sirtuin-1的PPAR和转录因子PRDM-16的脱乙酰化，并促进PPAR-PRDM-16相互作用以诱导Wat褐变。饮食辣椒素不能保护TRPV1(-/-)小鼠不受肥胖的影响。结论和解释我们的结果首次表明，饮食辣椒素激活TRPV1通道会触发Wat的褐变，从而抵消肥胖。我们的结果表明，激活TRPV1通道是一种很有前途的对抗肥胖的策略。
Background and PurposeThe growing epidemic of obesity and metabolic diseases necessitates the development of novel strategies to prevent and treat such diseases. Current research suggests that browning of white adipose tissue (WAT) promotes energy expenditure to counter obesity. Recent research suggests that activation of the TRPV1 channels counters obesity. However, the mechanism by which activation of TRPV1 channels counters obesity still remains unclear.Experimental ApproachWe evaluated the effect of dietary capsaicin to induce a browning program in WAT by activating TRPV1 channels to prevent diet-induced obesity using wild-type and TRPV1(-/-) mouse models. We performed experiments using preadipocytes and fat pads from these mice.Key ResultsCapsaicin stimulated the expression of brown fat-specific thermogenic uncoupling protein-1 and bone morphogenetic protein-8b in WAT. Capsaicin triggered browning of WAT by promoting sirtuin-1 expression and activity via TRPV1 channel-dependent elevation of intracellular Ca2+ and phosphorylation of Ca2+/calmodulin-activated protein kinase II and AMP-activated kinase. Capsaicin increased the expression of PPAR 1 coactivator and enhanced metabolic and ambulatory activity. Further, capsaicin stimulated sirtuin-1-dependent deacetylation of PPAR and the transcription factor PRDM-16 and facilitated PPAR-PRDM-16 interaction to induce browning of WAT. Dietary capsaicin did not protect TRPV1(-/-) mice from obesity.Conclusions and InterpretationsOur results show for the first time that activation of TRPV1 channels by dietary capsaicin triggers browning of WAT to counteract obesity. Our results suggest that activation of TRPV1 channels is a promising strategy to counter obesity.