2012年9月28日 電 /生物谷BIOON/ --近日，Dana-Farber癌癥研究所科學(xué)家證實(shí)翻轉(zhuǎn)在白色脂肪細(xì)胞中新發(fā)現(xiàn)的一種分子開關(guān),，可以使老鼠即使在吃高熱量的飲食情況下也不會(huì)變得肥胖或?qū)е轮炯?xì)胞發(fā)生炎癥反應(yīng),。
相關(guān)研究結(jié)果將刊登在9月28日的Cell雜志上，該研究發(fā)現(xiàn)了一個(gè)能將生熱作用（燃燒卡路里產(chǎn)生熱量）和脂肪細(xì)胞中炎癥的發(fā)展聯(lián)系起來的分子,。這兩個(gè)過程先前被認(rèn)為是獨(dú)立的,。生熱作用在代謝和保持健康體重中起著重要的作用，而炎癥觸發(fā)胰島素抵抗引發(fā)糖尿病,。研究人員Bruce Spiegelman博士等發(fā)現(xiàn)這個(gè)開關(guān)分子TRPV4蛋白質(zhì)在存儲(chǔ)多余熱量的白色脂肪細(xì)胞中是高表達(dá)的,。
在這項(xiàng)研究中，研究人員培育出缺乏TRPV4的小鼠,。在TRPV4不存在的情況下,，白細(xì)胞打開開啟一組基因，消耗能量以產(chǎn)生熱量,，而不是存儲(chǔ)能量成為多余的脂肪,。這種“生熱”過程通常發(fā)生在小動(dòng)物和人類嬰兒應(yīng)對(duì)寒冷環(huán)境時(shí)的棕色或米色脂肪中,。
TRPV4缺陷小鼠被給予一個(gè)高熱量飲食好幾個(gè)星期,，但這些小鼠并沒有變得肥胖，自身脂肪細(xì)胞炎癥和胰島素抵抗的水平反而降低了,。Spiegelman說：我們已經(jīng)確定了上述現(xiàn)象的具體調(diào)控蛋白,，當(dāng)該蛋白被抑制時(shí)可激活米色脂肪組織，抑制炎癥反應(yīng)TRPV4的角色是調(diào)節(jié)脂肪細(xì)胞的生熱作用和炎性反應(yīng),，因此為治療肥胖及相關(guān)代謝性疾病提供了一個(gè)潛在靶點(diǎn),。（生物谷Bioon.com）
doi:10.1016/j.cell.2012.08.034
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TRPV4 Is a Regulator of Adipose Oxidative Metabolism, Inflammation, and Energy Homeostasis
Li Ye, Sandra Kleiner, Jun Wu, Rajan Sah, Rana K. Gupta, Alexander S. Banks, Paul Cohen, Melin J. Khandekar, Pontus Bostr?m, Rina J. Mepani, Dina Laznik, Theodore M. Kamenecka, Xinyi Song, Wolfgang Liedtke, Vamsi K. Mootha, Pere Puigserver, Patrick R. Griffin, David E. Clapham, Bruce M. Spiegelman
PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1α expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1α, UCP1, and cellular respiration. Additionally, it potently controlled the expression of multiple proinflammatory genes involved in the development of insulin resistance. Mice with a null mutation for TRPV4 or wild-type mice treated with a TRPV4 antagonist showed elevated thermogenesis in adipose tissues and were protected from diet-induced obesity, adipose inflammation, and insulin resistance. This role of TRPV4 as a cell-autonomous mediator for both the thermogenic and proinflammatory programs in adipocytes could offer a target for treating obesity and related metabolic diseases.
