人體的脂肪分為白色和棕色兩種,。白色脂肪細胞會儲存攝入體內(nèi)的多余熱量,,如在體內(nèi)積聚過多,,就會形成肥胖,。棕色脂肪則是一種天然耗能型脂肪,,對于維持體溫和能量平衡起著重要的作用,,其細胞中含有大量的線粒體,,可通過燃燒攝入的糖來產(chǎn)生熱量,,而不是以脂肪形式將其存儲起來,。喬斯林糖尿病中心(Joslin Diabetes Center)的一個研究小組曾在去年的研究中證實了棕色脂肪在成人體內(nèi)的活性作用,,近日研究人員再度發(fā)現(xiàn)小鼠白色脂肪組織和骨骼肌中的祖細胞可轉(zhuǎn)化為棕色脂肪細胞。研究論文在線發(fā)表在PNAS雜志上,。
“新研究發(fā)現(xiàn)為研究人員開辟了一條全新的途徑以設(shè)計出誘導(dǎo)內(nèi)源祖細胞分化為成熟的棕色脂肪細胞的新分子,,”論文的資深作者,、哈佛大學(xué)醫(yī)學(xué)院醫(yī)學(xué)系助理教授,、喬斯林糖尿病中心研究員Yu-Hua Tseng博士說,。
“這是一個特別令人興奮的發(fā)現(xiàn),,我們證實其中的一些細胞就位于皮下的白色脂肪組織中,。這意味著獲得這些細胞對于我們來說并不是很難的事情,”Tseng說,。
在新研究中科學(xué)家們對來自小鼠不同脂肪組織和骨骼肌的細胞進行了體外實驗檢測,,研究人員首先用一種稱為Sca1的蛋白標記細胞,然后再用BMP-7蛋白(從前證實是棕色脂肪分化的一個關(guān)鍵因子)處理這些細胞,。研究人員發(fā)現(xiàn)其中大量的細胞均表達棕色脂肪細胞的標記物,。當在細胞中加入糖尿病羅格列酮時,,研究人員發(fā)現(xiàn)皮下白色脂肪組織中祖細胞的轉(zhuǎn)換率明顯升高。過去的研究曾證實羅格列酮可推動棕色脂肪細胞分化,。進而研究人員證實盡管來自不同小鼠脂肪組織和肌肉組織的Sca1陽性祖細胞在分子標記上存在在差異,,它們卻一致地發(fā)生了轉(zhuǎn)變。而當研究人員將BMP-7處理的祖細胞重新注射到小鼠體內(nèi),研究人員發(fā)現(xiàn)這些細胞全都存活并轉(zhuǎn)化形成了成熟的棕色脂肪細胞,。
“目前我們?nèi)匀辉趯ふ胰梭w內(nèi)與Sca1 蛋白相似物,,”Tseng說:“我們同時還對來自不同類型人類脂肪組織的細胞進行了檢測,,我們發(fā)現(xiàn)BMP-7可以誘導(dǎo)來源于人類白色脂肪組織的細胞表達分化棕色脂肪細胞的標記物,。”
“鑒于肥胖是2型糖尿病,、心血管疾病和其他代謝性疾病的主要風(fēng)險因子,,找到能減輕體重的新方法是非常必要的,,”Tseng說:“當然對于一般人群而言飲食和鍛煉仍是減重最好的方法,。但是對于那些具有肥胖遺傳體質(zhì)或是由于體重超標而導(dǎo)致代謝性疾病的人,則迫切需要找到一種高效安全的減肥方法,。新研究結(jié)果朝利用棕色脂肪細胞進行疾病治療邁出了非常重要的一步。”(生物谷Bioon.com)
生物谷推薦原文出處:
PNAS doi: 10.1073/pnas.1010929108
Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat
Tim J. Schulza,b, Tian Lian Huanga, Thien T. Trana, Hongbin Zhanga, Kristy L. Townsenda, Jennifer L. Shadracha,b,c,d, Massimiliano Cerlettia,b,c, Lindsay E. McDougalla, Nino Giorgadzee, Tamara Tchkoniae, Denis Schrierf, Dean Falbf, James L. Kirklande, Amy J. Wagersa,b,c,d, and Yu-Hua Tsenga,b,1
Abstract
Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1+/CD45?/Mac1?; referred to as Sca-1+ progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1+ cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.