Nature：脂肪與肌肉之間的聯系

專題：Nature報道

本期封面所示為棕色脂肪，在其中，PRDM16的表達被shRNA抑制，肌肉細胞標記為紅色，脂肪細胞和其他細胞類型標記為藍色核。封面美術：Eric Smith。

人體中有兩種類型的脂肪組織：一種是棕色脂肪，主要功能是燃燒卡路里，產生身體所需熱量；另一種是白色脂肪，用來儲存能量。

現在，研究人員獲得一個令人吃驚的發現：棕色脂肪是骨骼肌的一種衍生物。這一發現也許會促使我們去重新思考我們關于這兩種組織之間關系的觀點。以前，關于脂肪發育的大多數模型都認為，棕色和白色脂肪細胞來自同一種成脂肪前體細胞，但體內細胞系跟蹤研究表明，棕色脂肪細胞起源于表達Myf5基因（迄今只在肌肉細胞中發現的一種標記）的成骨細胞。PRDM16（一種鋅指蛋白，已知能夠刺激棕色脂肪選擇性基因表達）可強有力地調控肌肉與棕色脂肪之間的雙向細胞命運轉換。作為棕色脂肪細胞命運的一種支配性調控因子，PRDM16在治療肥胖癥上可能有潛在用途，能夠誘導PRDM16在白色脂肪或肌肉前體中表達的化合物也可能有這種作用。

推薦原始出處：

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.