Nature：脂肪与肌肉之间的联系

专题：Nature报道

本期封面所示为棕色脂肪，在其中，PRDM16的表达被shRNA抑制，肌肉细胞标记为红色，脂肪细胞和其他细胞类型标记为蓝色核。封面美术：Eric Smith。

人体中有两种类型的脂肪组织：一种是棕色脂肪，主要功能是燃烧卡路里，产生身体所需热量；另一种是白色脂肪，用来储存能量。

现在，研究人员获得一个令人吃惊的发现：棕色脂肪是骨骼肌的一种衍生物。这一发现也许会促使我们去重新思考我们关于这两种组织之间关系的观点。以前，关于脂肪发育的大多数模型都认为，棕色和白色脂肪细胞来自同一种成脂肪前体细胞，但体内细胞系跟踪研究表明，棕色脂肪细胞起源于表达Myf5基因（迄今只在肌肉细胞中发现的一种标记）的成骨细胞。PRDM16（一种锌指蛋白，已知能够刺激棕色脂肪选择性基因表达）可强有力地调控肌肉与棕色脂肪之间的双向细胞命运转换。作为棕色脂肪细胞命运的一种支配性调控因子，PRDM16在治疗肥胖症上可能有潜在用途，能够诱导PRDM16在白色脂肪或肌肉前体中表达的化合物也可能有这种作用。

推荐原始出处：

Nature 454, 961-967 (21 August 2008) | doi:10.1038/nature07182

PRDM16 controls a brown fat/skeletal muscle switch

Patrick Seale1, Bryan Bjork2, Wenli Yang1, Shingo Kajimura1, Sherry Chin1, Shihuan Kuang3, Anthony Scimè3, Srikripa Devarakonda1, Heather M. Conroe1, Hediye Erdjument-Bromage4, Paul Tempst4, Michael A. Rudnicki3, David R. Beier2 & Bruce M. Spiegelman1

Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA
Genetics Division, Brigham and Women’s Hospital, Harvard Medical School, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
The Sprott Center for Stem Cell Research, Ottawa Health Research Institute, Molecular Medicine Program, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA

Brown fat can increase energy expenditure and protect against obesity through a specialized program of uncoupled respiration. Here we show by in vivo fate mapping that brown, but not white, fat cells arise from precursors that express Myf5, a gene previously thought to be expressed only in the myogenic lineage. We also demonstrate that the transcriptional regulator PRDM16 (PRD1-BF1-RIZ1 homologous domain containing 16) controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation. Conversely, ectopic expression of PRDM16 in myoblasts induces their differentiation into brown fat cells. PRDM16 stimulates brown adipogenesis by binding to PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and activating its transcriptional function. Finally, Prdm16-deficient brown fat displays an abnormal morphology, reduced thermogenic gene expression and elevated expression of muscle-specific genes. Taken together, these data indicate that PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis.