ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes

Science Translational Medicine

Volumn 6, Issue 247, 2014, Pages

  Ussar, Siegfried ^a,b   Lee, Kevin Y ^a   Dankel, Simon N ^a,c,d   Boucher, Jeremie ^a,e   Haering, Max Felix ^a   Kleinridders, Andre ^a   Thomou, Thomas ^a   Xue, Ruidan ^a   Macotela, Yazmin ^a,f   Cypess, Aaron M ^a   Tseng, Yu Hua ^a   Mellgren, Gunnar ^c,d   Kahn, C Ronald ^a  

^a JOSLIN DIABETES CENTER   (United States)

^b INSTITUTE OF EPIDEMIOLOGY   (Germany)

^c UNIVERSITY OF BERGEN   (Norway)

^d HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^e ASTRAZENECA R AND D   (Sweden)

^f INSTITUTO DE NEUROBIOLOGÍA   (Mexico)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPONECTIN; CELL SURFACE PROTEIN; PROTEIN ASC 1; PROTEIN P2RX5; PROTEIN PAT2; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1; AMINO ACID TRANSPORTER; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; BIOLOGICAL MARKER; COTRANSPORTER; P2RX5 PROTEIN, HUMAN; P2RX5 PROTEIN, MOUSE; PURINERGIC P2X5 RECEPTOR; SLC36A2 PROTEIN, HUMAN; SLC36A2 PROTEIN, MOUSE; SLC7A10 PROTEIN, HUMAN; SLC7A10 PROTEIN, MOUSE;

ADIPOSE TISSUE; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BEIGE ADIPOSE TISSUE; BROWN ADIPOSE TISSUE; CELL DIFFERENTIATION; CELL SURFACE; CLINICAL ARTICLE; COMPUTER MODEL; CONTROLLED STUDY; FEMALE; GENETIC DATABASE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; REGULATORY MECHANISM; WHITE ADIPOSE TISSUE; 129 MOUSE; ANIMAL; BIOLOGY; BROWN ADIPOCYTE; C57BL MOUSE; CELL MEMBRANE; COLD; DISEASE MODEL; DRUG EFFECTS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; OBESITY; TIME; WHITE ADIPOCYTE;

ADIPOCYTES, BROWN; ADIPOCYTES, WHITE; ADRENERGIC BETA-3 RECEPTOR AGONISTS; AMINO ACID TRANSPORT SYSTEM Y+; AMINO ACID TRANSPORT SYSTEMS, NEUTRAL; ANIMALS; BIOMARKERS; CELL MEMBRANE; COLD TEMPERATURE; COMPUTATIONAL BIOLOGY; DISEASE MODELS, ANIMAL; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HUMANS; MALE; MICE; MICE, 129 STRAIN; MICE, INBRED C57BL; OBESITY; RECEPTORS, PURINERGIC P2X5; SYMPORTERS; TIME FACTORS;

EID: 84926486610     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3008490     Document Type: Article

References (34)

1. T. Tchkonia, M. Lenburg, T. Thomou, N. Giorgadze, G. Frampton, T. Pirtskhalava, A. Cartwright, M. Cartwright, J. Flanagan, I. Karagiannides, N. Gerry, R. A. Forse, Y. Tchoukalova, M. D. Jensen, C. Pothoulakis, J. L. Kirkland, Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns. Am. J. Physiol. Endocrinol. Metab. 292, E298-E307 (2007). (Pubitemid 46052953)
2. J. S. Flier, Obesity wars: Molecular progress confronts an expanding epidemic. Cell 116, 337-350 (2004). (Pubitemid 38167322)
3. J. Boucher, M. A. Mori, K. Y. Lee, G. Smyth, C. W. Liew, Y. Macotela, M. Rourk, M. Bluher, S. J. Russell, C. R. Kahn, Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling. Nat. Commun. 3, 902 (2012).
4. R. Atit, S. K. Sgaier, O. A. Mohamed, M. M. Taketo, D. Dufort, A. L. Joyner, L. Niswander, R. A. Conlon, β-Catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse. Dev. Biol. 296, 164-176 (2006). (Pubitemid 44061762)
5. P. Seale, B. Bjork, W. Yang, S. Kajimura, S. Chin, S. Kuang, A. Scimè, S. Devarakonda, H. M. Conroe, H. Erdjument-Bromage, P. Tempst, M. A. Rudnicki, D. R. Beier, B. M. Spiegelman, PRDM16 controls a brown fat/skeletal muscle switch. Nature 454, 961-967 (2008).
6. Y. H. Tseng, A. M. Cypess, C. R. Kahn, Cellular bioenergetics as a target for obesity therapy. Nat. Rev. Drug Discov. 9, 465-482 (2010).
7. J. Wu, P. Boström, L. M. Sparks, L. Ye, J. H. Choi, A. H. Giang, M. Khandekar, K. A. Virtanen, P. Nuutila, G. Schaart, K. Huang, H. Tu, W. D. van Marken Lichtenbelt, J. Hoeks, S. Enerbäck, P. Schrauwen, B. M. Spiegelman, Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366-376 (2012).
8. W. Liu, T. Shan, X. Yang, S. Liang, P. Zhang, Y. Liu, X. Liu, S. Kuang, A heterogeneous lineage origin underlies the phenotypic and molecular differences of white and beige adipocytes. J. Cell Sci. 126, 3527-3532 (2013).
9. M. Rosenwald, A. Perdikari, T. Rülicke, C. Wolfrum, Bi-directional interconversion of brite and white adipocytes. Nat. Cell Biol. 15, 659-667 (2013).
10. S. Gesta, M. Blüher, Y. Yamamoto, A. W. Norris, J. Berndt, S. Kralisch, J. Boucher, C. Lewis, C. R. Kahn, Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc. Natl. Acad. Sci. U. S. A. 103, 6676-6681 (2006).
11. K. I. Stanford, R. J. Middelbeek, K. L. Townsend, D. An, E. B. Nygaard, K. M. Hitchcox, K. R. Markan, K. Nakano, M. F. Hirshman, Y. H. Tseng, L. J. Goodyear, Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J. Clin. Invest. 123, 215-223 (2013).
12. M. Saito, Y. Okamatsu-Ogura, M. Matsushita, K. Watanabe, T. Yoneshiro, J. Nio-Kobayashi, T. Iwanaga, M. Miyagawa, T. Kameya, K. Nakada, Y. Kawai, M. Tsujisaki, High incidence of metabolically active brown adipose tissue in healthy adult humans: Effects of cold exposure and adiposity. Diabetes 58, 1526-1531 (2009).
13. A. M. Cypess, S. Lehman, G. Williams, I. Tal, D. Rodman, A. B. Goldfine, F. C. Kuo, E. L. Palmer, Y. H. Tseng, A. Doria, G. M. Kolodny, C. R. Kahn, Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509-1517 (2009).
14. W. D. van Marken Lichtenbelt, J. W. Vanhommerig, N. M. Smulders, J. M. Drossaerts, G. J. Kemerink, N. D. Bouvy, P. Schrauwen, G. J. Teule, Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360, 1500-1508 (2009).
15. A. M. Cypess, A. P. White, C. Vernochet, T. J. Schulz, R. Xue, C. A. Sass, T. L. Huang, C. Roberts-Toler, L. S. Weiner, C. Sze, A. T. Chacko, L. N. Deschamps, L. M. Herder, N. Truchan, A. L. Glasgow, A. R. Holman, A. Gavrila, P. O. Hasselgren, M. A. Mori, M. Molla, Y. H. Tseng, Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat. Med. 19, 635-639 (2013).
16. N. Z. Jespersen, T. J. Larsen, L. Peijs, S. Daugaard, P. Homøe, A. Loft, J. O. N. G. J. de, N. Mathur, B. Cannon, J. Nedergaard, B. K. Pedersen, K. Møller, C. Scheele, A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metab. 17, 798-805 (2013).
17. T. B. Waldén, I. R. Hansen, J. A. Timmons, B. Cannon, J. Nedergaard, Recruited vs. nonrecruited molecular signatures of brown, "brite", and white adipose tissues. Am. J. Physiol. Endocrinol. Metab. 302, E19-E31 (2012).
18. K. Y. Lee, S. J. Russell, S. Ussar, J. Boucher, C. Vernochet, M. A. Mori, G. Smyth, M. Rourk, C. Cederquist, E. D. Rosen, B. B. Kahn, C. R. Kahn, Lessons on conditional gene targeting in mouse adipose tissue. Diabetes 62, 864-874 (2013).
19. Y. Fukasawa, H. Segawa, J. Y. Kim, A. Chairoungdua, D. K. Kim, H. Matsuo, S. H. Cha, H. Endou, Y. Kanai, Identification and characterization of a Na+-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D- and L-amino acids. J. Biol. Chem. 275, 9690-9698 (2000). (Pubitemid 30185202)
20. J. Nakauchi, H. Matsuo, D. K. Kim, A. Goto, A. Chairoungdua, S. H. Cha, J. Inatomi, Y. Shiokawa, K. Yamaguchi, I. Saito, H. Endou, Y. Kanai, Cloning and characterization of a human brain Na+-independent transporter for small neutral amino acids that transports D-serine with high affinity. Neurosci. Lett. 287, 231-235 (2000). (Pubitemid 30339391)
21. Y. Macotela, B. Emanuelli, M. A. Mori, S. Gesta, T. J. Schulz, Y. H. Tseng, C. R. Kahn, Intrinsic differences in adipocyte precursor cells from different white fat depots. Diabetes 61, 1691-1699 (2012).
22. J. A. Cox, O. Barmina, M. M. Voigt, Gene structure, chromosomal localization, cDNA cloning and expression of themouse ATP-gated ionotropic receptor P2X5 subunit. Gene 270, 145-152 (2001). (Pubitemid 32525810)
23. K. T. Lê, M. Paquet, D. Nouel, K. Babinski, P. Ségué la, Primary structure and expression of a naturally truncated human P2X ATP receptor subunit from brain and immune system. FEBS Lett. 418, 195-199 (1997). (Pubitemid 27514445)
24. Y. Yamamoto, S. Gesta, K. Y. Lee, T. T. Tran, P. Saadatirad, C. R. Kahn, Adipose depots possess unique developmental gene signatures. Obesity 18, 872-878 (2010).
25. V. L. Veum, S. N. Dankel, J. Gjerde, H. J. Nielsen, M. H. Solsvik, C. Haugen, B. J. Christensen, T. Hoang, D. J. Fadnes, C. Busch, V. Våge, J. V. Sagen, G. Mellgren, The nuclear receptors NUR77, NURR1 and NOR1 in obesity and during fat loss. Int. J. Obes. 36, 1195-1202 (2012).
26. S. Gesta, Y. H. Tseng, C. R. Kahn, Developmental origin of fat: Tracking obesity to its source. Cell 131, 242-256 (2007). (Pubitemid 47576146)
27. M. E. Lidell, M. J. Betz, S. Enerbäck, Two types of brown adipose tissue in humans. Adipocyte 3, 63-66 (2014).
28. A. R. Rutter, R. L. Fradley, E. M. Garrett, K. L. Chapman, J. M. Lawrence, T. W. Rosahl, S. Patel, Evidence from gene knockout studies implicates Asc-1 as the primary transporter mediating D-serine reuptake in the mouse CNS. Eur. J. Neurosci. 25, 1757-1766 (2007). (Pubitemid 46550015)
29. X. Xie, T. Dumas, L. Tang, T. Brennan, T. Reeder, W. Thomas, R. D. Klein, J. Flores, B. F. O'Hara, H. C. Heller, P. Franken, Lack of the alanine-serine-cysteine transporter 1 causes tremors, seizures, and early postnatal death in mice. Brain Res. 1052, 212-221 (2005). (Pubitemid 41116780)
30. M. Garcia-Guzman, F. Soto, B. Laube, W. Stühmer, Molecular cloning and functional expression of a novel rat heart P2X purinoceptor. FEBS Lett. 388, 123-127 (1996). (Pubitemid 26226344)
31. R. A. North, Molecular physiology of P2X receptors. Physiol. Rev. 82, 1013-1067 (2002).
32. J. Nedergaard, B. Cannon, UCP1 mRNA does not produce heat. Biochim. Biophys. Acta 1831, 943-949 (2013).
33. Y. C. Chen, A. M. Cypess, Y. C. Chen, M. Palmer, G. Kolodny, C. R. Kahn, K. K. Kwong, Measurement of human brown adipose tissue volume and activity using anatomic MR imaging and functional MR imaging. J. Nucl. Med. 54, 1584-1587 (2013).
34. S. Ussar, O. Bezy, M. Blüher, C. R. Kahn, Glypican-4 enhances insulin signaling via interaction with the insulin receptor and serves as a novel adipokine. Diabetes 61, 2289-2298 (2012).