Brown Adipose Tissue Differentiation and Control Mechanism
Abstract: Humans and other mammals have two main adipose tissue depots: white adipose tissue (include visceral- and subcutaneous- white adipose tissue), and brown adipose tissue, each of which possesses unique cell-autonomous properties. In contrast to visceral adipose tissue, which can induce detrimental metabolic ef-fects, subcutaneous white adipose tissue and brown adipose tissue have the potential to benefit metabolism by improving glucose homeostasis and increasing energy consumption. BMP7 (bone morphogenetic proteins7) is one of members of the transforming growth factor-β (TGF-β) superfamily and control multiple key steps of embryonic development and differentiation. In recent studies, people found that BMP7-induced UCP1 ex-pression was markedly diminished in brown preadipocytes deficient in both PRDM16 and PGC (PGC-1α and PGC-1β), it ultimately induces BAT mitochondrial cells in the biological production and cell differentiation. There are two ways in development of brown adipose tissue. These researches indicate the potential to treat obesity and related diseases through activating BMP7 and PRDM16 to produce brown adipose tissue. Re-cently, using 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans showed that adults retain metabolically active BAT depots that can be induced in response to cold and sympathetic nervous system activation. These findings high light BAT as a potenial relevant tar get for pharmacological and gene expression manipulation to combat human obesity. We reviewed the recent re-search progresses of BAT in human and its potential functional significance.
文章引用: 张麟 , 朱万龙 , 蔡金红 , 练硝 , 王政昆 (2011) 褐色脂肪组织分化及其调节机制研究进展。 生物过程， 1， 13-17. doi: 10.12677/bp.2011.12004
 P. Seale, B. Bjork, W. Yang, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature, 2008, 454(7207): 961-967.
 S. Cinti. The adipose organ. Prostaglandins leukot. Essential Fat Acids, 2005, 73: 9-15.
 B. Cannon, J. Nedergaard. Brown adipose tissue: Function and physiological significance. Physiological Reviews, 2004, 84(1): 277-359.
 S. R. Farmer. Molecular determinants of brown adipocyte forma- tion and functio. Genes & De-velopment, 2008, 22: 1269-1275.
 T. T. Tran, C. R. Kahn. Transplantation of adipose tissue and stem cells: role in metabolism and disease. Nature Reviews Endocrinology, 2010, 6: 195-213.
 K. A. Virtanen, M. E. Lidell, J. Orava, et al. Functional brown adipose tissue in healthy adults. The New England Journal of Medicine, 2009, 360: 1518-1525.
 S. Cinti. Transdifferentiation properties of adipocytes in the adipose organ. American Journal of Physiology, 2009, 297(5): E977-E986.
 V. Azzu, M. D. Brand. Degradation of an intramito-chondrial pro- tein by the cytosolic proteasome. Journal of Cell Science, 2010, 123: 578-585.
 G. Frühbeck, P. Sesma and M. A. Burrel. PRDM16: The interconvertible adipo-myocyte switch. Cell Biology, 2009, 19(4): 141- 146.
 B. Cannon, J. Nedergaard. Developmental biology: Neither fat nor flesh. Nature, 2008, 454(7207): 947-948.
 J. A. Timmons, K. Wennmalm, O. Larsson, et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. The Proceeding of National Academic Science USA, 2007, 104(11): 4401-4406.
 M. Crisan, L. Casteilla, L. Lehr, et al. A reservoir of brown adi- pocyte progenitors in human. Skeletal Muscle, 2008, 26(9): 2425- 2433.
 N. Ijichi, K. Ikeda, K. Horie-Inoue, et al. Estrogen-related receptor alpha modulates the expression of adipogenesis-related genes during adipocyte differentiation. Biochemical and Biophysical Research Communications, 2007, 358(3): 813-818.
 M. Uldry, W. Yang, J. St-Pierre, et al. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metabolism, 2006, 3(5): 333-341.
 E. Canalis, A. N. Economides and E. Gazzerro. Bone morphogenetic proteins,their antagonists, and the skeleton. Endocrine Reviews, 2003, 24(2): 218-235.
 C. Song, Z. Guo, Q. Ma, et al. Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochemical and Biophysical Research Communications, 2003, 308(3): 458-462.
 E. Balint, D. Lapointe, H. Drissi, et al. Phenotype discovery by gene expression profiling: Mapping of biological processes linked to BMP-2-mediated osteoblast differentiation. Journal of Cellular Biochemistry, 2003, 89(2): 401-426.
 Y. H. Tseng, E. Kokkotou, T. J. Schulz1, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy ex- penditure. Nature, 2008, 454: 1000-1004.
 J. J. Sekelsky, S. J. Newfeld, L. A. Reftery, et al. Genetic cha-racteri-zation and cloning of mothers againstdpp, a gene required for decapentap legic function in Drosophila melanogaster. Genetics, 1995, 139(3): 1347-1358.
 T. Imamura, M. Takase, A. Nishihara, et al. Smad 6 inhibits sig- naling by the TGF-β superfamily. Nature, 1997, 389(6651): 622- 626.
 N. Mochizuki, S. Shimizu, T. Nagasawa, et al. A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/ EVI1 gene and is transcriptionally activated in t(1;3) (p36;q21)- positive leukemia cells. Blood, 2000, 96(9): 3209-3214.
 P. Seale, S. Kajimura, W. Yang, et al. Transcriptional control of brown fat determination by PRDM16. Cell Biology, 2007, 6(1): 38-54.
 G. Chinnadurai. Transcriptional regulation by C-terminal binding proteins. International Journal of Biochemical Cell Biology, 2007, 39(9): 1593-1607.
 S. Kajimura, P. Seale, T. Tomaru, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes & Devices, 2008, 22(10): 1397-1409.
 S. R. Farmer. Molecular determinants of brown adipocyte forma- tion and function. Genes & Devices, 2008, 22(10): 1269-1275.
 S. R. Farmer. Brown fat and skeletal muscle: Unlikely cousins? Cell, 2008, 134(5): 726-727.
 S. Gesta, Y. H. Tseng and C. R. Kahn. Developmental origin of fat: Tracking obesity to its source. Cell, 2007, 131(2): 242-256.