Improved methodologies for the study of adipose biology: Insights gained and opportunities ahead

Journal of Lipid Research

Volumn 55, Issue 4, 2014, Pages 605-624

  Wang, Qiong A ^a   Scherer, Philipp E ^a,b   Gupta, Rana K ^a  

^a Department of Internal Medicine Touchstone Diabetes Center ^*  (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Adipogenesis; Energy metabolism; Obesity

Indexed keywords

ADIPOCYTOKINE; CRE RECOMBINASE; FATTY ACID BINDING PROTEIN 4;

ADIPOCYTE; ADIPOGENESIS; BODY FAT DISTRIBUTION; BROWN ADIPOSE TISSUE; CELL DIFFERENTIATION; CELL FUNCTION; CELL LINEAGE; CELL TRANSPLANTATION; ENERGY METABOLISM; FAT MASS; GENE EXPRESSION; GENE TARGETING; GLUCOSE METABOLISM; HUMAN; HYPOXEMIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID METABOLISM; LIPID STORAGE; LIPOGENESIS; LIPOLYSIS; MACROPHAGE; MESENCHYME CELL; MITOCHONDRION; NONHUMAN; OBESITY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; WHITE ADIPOSE TISSUE; ADIPOSE TISSUE; ANIMAL; ANIMAL MODEL; ANTIBODY SPECIFICITY; CELL TRACKING; CULTURE TECHNIQUE; CYTOLOGY; PHYSIOLOGY;

ADIPOCYTES; ADIPOGENESIS; ADIPOSE TISSUE; ANIMALS; CELL CULTURE TECHNIQUES; CELL LINEAGE; CELL TRACKING; ENERGY METABOLISM; GENE EXPRESSION; HUMANS; LIPID METABOLISM; MODELS, ANIMAL; ORGAN SPECIFICITY;

EID: 84897413090     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.R046441     Document Type: Review

References (219)

1. Green, H., and O. Kehinde. 1974. Sublines of mouse 3T3 cells that accumulate lipid. Cell. 1 : 113-116.
2. Rosen, E. D., and B. M. Spiegelman. 2014. What we talk about when we talk about fat. Cell. 156 : 20-44.
3. Cristancho, A. G., and M. A. Lazar. 2011. Forming functional fat: a growing understanding of adipocyte differentiation. Nat. Rev. Mol. Cell Biol. 12 : 722-734.
4. Cannon, B., and J. Nedergaard. 2004. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84 : 277-359.
5. Gesta, S., M. Bluher, Y. Yamamoto, A. W. Norris, J. Berndt, S. Kralisch, J. Boucher, C. Lewis, and C. R. Kahn. 2006. Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc. Natl. Acad. Sci. USA. 103 : 6676-6681.
6. Vidal, H. 2001. Gene expression in visceral and subcutaneous adipose tissues. Ann. Med. 33 : 547-555.
7. Vohl, M. C., R. Sladek, J. Robitaille, S. Gurd, P. Marceau, D. Richard, T. J. Hudson, and A. Tchernof. 2004. A survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men. Obes. Res. 12 : 1217-1222.
8. Kissebah, A. H., and G. R. Krakower. 1994. Regional adiposity and morbidity. Physiol. Rev. 74 : 761-811.
9. Seale, P., B. Bjork, W. Yang, S. Kajimura, S. Chin, S. Kuang, A. Scime, S. Devarakonda, H. M. Conroe, H. Erdjument-Bromage, et al. 2008. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 454 : 961-967.
10. Wu, J., P. Boström, L. M. Sparks, L. Ye, J. H. Choi, A-H. Giang, M. Khandekar, K. A. Virtanen, P. Nuutila, G. Schaart, et al. 2012. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 150 : 366-376.
11. Wu, J., P. Cohen, and B. M. Spiegelman. 2013. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev. 27 : 234-250.
12. Villanueva, C. J., L. Vergnes, J. Wang, B. G. Drew, C. Hong, Y. Tu, Y. Hu, X. Peng, F. Xu, E. Saez, et al. 2013. Adipose subtype-selective recruitment of TLE3 or Prdm16 by PPAR γ specifies lipid storage versus thermogenic gene programs. Cell Metab. 17 : 423-435.
13. Seale, P., S. Kajimura, W. Yang, S. Chin, L. M. Rohas, M. Uldry, G. Tavernier, D. Langin, and B. M. Spiegelman. 2007. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 6 : 38-54.
14. Uldry, M., W. Yang, J. St-Pierre, J. Lin, P. Seale, and B. M. Spiegelman. 2006. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation.Cell Metab. 3 : 333-341.
15. Rajakumari, S., J. Wu, J. Ishibashi, H. W. Lim, A. H. Giang, K. J.Won, R. R. Reed, and P. Seale. 2013. EBF2 determines and maintains brown adipocyte identity. Cell Metab. 17 : 562-574
16. Puigserver, P., Z. Wu, C. W. Park, R. Graves, M. Wright, and B. M. Spiegelman. 1998. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 92 : 829-839.
17. Cohen, P., J. D. Levy, Y. Zhang, A. Frontini, D. P. Kolodin, K. J. Svensson, J. C. Lo, X. Zeng, L. Ye, M. J. Khandekar, et al. 2014. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell. 156 : 304-316.
18. Lee, K. Y., Y. Yamamoto, J. Boucher, J. N. Winnay, S. Gesta, J. Cobb, M. Blüher, and C. R. Kahn. 2013. Shox2 is a molecular determinant of depot-specific adipocyte function. Proc. Natl. Acad. Sci. USA. 110 : 11409-11414.
19. Xu, L., V. Panel, X. Ma, C. Du, L. Hugendubler, O. Gavrilova, A. Liu, T. McLaughlin, K. H. Kaestner, and E. Mueller. 2013. The winged helix transcription factor foxa3 regulates adipocyte differentiationand depot-selective fat tissue expansion. Mol. Cell. Biol. 33 : 3392-3399.
20. Jaworski, K., E. Sarkadi-Nagy, R. E. Duncan, M. Ahmadian, and H.S. Sul. 2007. Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue. Am. J. Physiol. Gastrointest. Liver Physiol. 293 : G1-G4.
21. Rohm, M., A. Sommerfeld, D. Strzoda, A. Jones, T. P. Sijmonsma, G. Rudofsky, C. Wolfrum, C. Sticht, N. Gretz, M. Zeyda, et al. 2013. Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue. Cell Metab. 17 : 575-585.
22. Fujimoto, Y., Y. Nakagawa, A. Satoh, K. Okuda, A. Shingyouchi, A. Naka, T. Matsuzaka, H. Iwasaki, K. Kobayashi, N. Yahagi, et al. 2013. TFE3 controls lipid metabolism in adipose tissue of male mice by suppressing lipolysis and thermogenesis. Endocrinology 154 : 3577-3588.
23. Eguchi, J., X. Wang, S. Yu, E. E. Kershaw, P. C. Chiu, J. Dushay, J. L. Estall, U. Klein, E. Maratos-Flier, and E. D. Rosen. 2011. Transcriptional control of adipose lipid handling by IRF4. Cell Metab. 13 : 249-259.
24. Rodbell, M. 1964. Metabolism of isolated fat cells. I. Effects ofhormones on glucose metabolism and lipolysis. J. Biol. Chem. 239 : 375-380.
25. Hollenberg, C. H., and A. Vost. 1969. Regulation of DNA synthesis in fat cells and stromal elements from rat adipose tissue. J. Clin. Invest. 47 : 2485-2498.
26. Berry, R., E. Jeffery, and M. S. Rodeheffer. 2014. Weighing in onadipocyte precursors. Cell Metab. 19 : 8-20
27. Crossno, J. T., Jr ., S. M. Majka, T. Grazia, R. G. Gill, and D. J. Klemm. 2006. Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells. J. Clin. Invest. 116 : 3220-3228.
28. Majka, S. M., Y. Barak, and D. J. Klemm. 2011. Concise review: adipocyte origins: weighing the possibilities. Stem Cells. 29 : 1034-1040.
29. Majka, S. M., K. E. Fox, J. C. Psilas, K. M. Helm, C. R. Childs, A. S.Acosta, R. C. Janssen, J. E. Friedman, B. T. Woessner, T. R. Shade, et al. 2010. De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific. Proc. Natl. Acad. Sci. USA. 107 : 14781-14786.
30. Rodeheffer, M. S., K. Birsoy, and J. M. Friedman. 2008. Identification of white adipocyte progenitor cells in vivo. Cell. 135 : 240-249.
31. Berry, R., and M. S. Rodeheffer. 2013. Characterization of the adipocyte cellular lineage in vivo. Nat. Cell Biol. 15 : 302-308.
32. Takakura, N., H. Yoshida, Y. Ogura, H. Kataoka, and S. Nishikawa. 1997. PDGFR alpha expression during mouse embryogenesis: immunolocalization analyzed by whole-mount immunohistostaining using the monoclonal anti-mouse PDGFR alpha antibody APA5. J. Histochem. Cytochem. 45 : 883-893.
33. Joe, A. W., L. Yi, A. Natarajan, F. Le Grand, L. So, J. Wang, M. A. Rudnicki, and F. M. Rossi. 2010. Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat. Cell Biol. 12 : 153-163.
34. Lee, Y. H., A. P. Petkova, E. P. Mottillo, and J. G. Granneman. 2012. In vivo identification of bipotential adipocyte progenitors recruited by beta3-adrenoceptor activation and high-fat feeding. Cell Metab. 15 : 480-491.
35. Uezumi, A., S. Fukada, N. Yamamoto, S. Takeda, and K. Tsuchida. 2010. Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat. Cell Biol. 12 : 143-152.
36. Wassermann, F. 1926. The fat organs of man: development, structure and systematic place of the so-called adipose tissue. Z. Zellforsch. Microskop. Anat. Abt. Histochem. 3 : 325-329.
37. Tang, W., D. Zeve, J. M. Suh, D. Bosnakovski, M. Kyba, R. E. Hammer, M. D. Tallquist, and J. M. Graff. 2008. White fat progenitor cells reside in the adipose vasculature. Science. 322 : 583-586.
38. Gupta, R. K., R. J. Mepani, S. Kleiner, J. C. Lo, M. J. Khandekar, P. Cohen, A. Frontini, D. C. Bhowmick, L. Ye, S. Cinti, et al. 2012. Zfp423 expression identifies committed preadipocytes and localizesto adipose endothelial and perivascular cells. Cell Metab. 15 : 230-239.
39. Wassermann, F. 1960. Electron microscopic investigation of the surface structures of the fat cell and of their changes during depletion of cell. Z. Zellforsch. Microsk. Anat. 52 : 778-800.
40. Napolitano, L. 1963. The differentiation of white adipose cells. an electron microscope study. J. Cell Biol. 18 : 663-679.
41. Shan, T., W. Liu, and S. Kuang. 2013. Fatty acid binding protein 4 expression marks a population of adipocyte progenitors in white and brown adipose tissues. FASEB J. 27 : 277-287.
42. Armani, A., C. Mammi, V. Marzolla, M. Calanchini, A. Antelmi, G. M. Rosano, A. Fabbri, and M. Caprio. 2010. Cellular models for understanding adipogenesis, adipose dysfunction, and obesity. J. Cell. Biochem. 110 : 564-572.
43. Poulos, S. P., M. V. Dodson, and G. J. Hausman. 2010. Cell line models for differentiation: preadipocytes and adipocytes. Exp. Biol. Med. (Maywood). 235 : 1185-1193.
44. Wolins, N. E., B. K. Quaynor, J. R. Skinner, A. Tzekov, C. Park, K.Choi, and P. E. Bickel. 2006. OP9 mouse stromal cells rapidly differentiate into adipocytes: characterization of a useful new model of adipogenesis. J. Lipid Res. 47 : 450-460.
45. Green, H., and M. Meuth. 1974. An established pre-adipose cell line and its differentiation in culture. Cell. 3 : 127-133.
46. Green, H., and O. Kehinde. 1975. An established preadipose cellline and its differentiation in culture II. Factors affecting the adipose conversion. Cell. 5 : 19-27.
47. Kuri-Harcuch, W., and H. Green. 1977. Increasing activity of enzymeson pathway of triacylglycerol synthesis during adipose conversion of 3T3 cells. J. Biol. Chem. 252 : 2158-2160.
48. Mandrup, S., T. M. Loftus, O. A. MacDougald, F. P. Kuhajda, and M. D. Lane. 1997. Obese gene expression at in vivo levels by fat pads derived from s.c. implanted 3T3-F442A preadipocytes. Proc.Natl. Acad. Sci. USA. 94 : 4300-4305.
49. Farmer, S. R. 2006. Transcriptional control of adipocyte formation. Cell Metab. 4 : 263-273.
50. Gupta, R. K., Z. Arany, P. Seale, R. J. Mepani, L. Ye, H. M. Conroe, Y. A. Roby, H. Kulaga, R. R. Reed, and B. M. Spiegelman. 2010. Transcriptional control of preadipocyte determination by Zfp423. Nature. 464 : 619-623.
51. Cristancho, A. G., M. Schupp, M. I. Lefterova, S. Cao, D. M. Cohen, C. S. Chen, D. J. Steger, and M. A. Lazar. 2011. Repressor transcription factor 7-like 1 promotes adipogenic competency in precursor cells. Proc. Natl. Acad. Sci. USA. 108 : 16271-16276.
52. Todaro, G. J., and H. Green. 1963. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J. Cell Biol. 17 : 299-313.
53. Siersbæk, R., R. Nielsen, S. John, M. H. Sung, S. Baek, A. Loft, G. L. Hager, and S. Mandrup. 2011. Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis. EMBO J. 30 : 1459-1472.
54. Nielsen, R., T. A. Pedersen, D. Hagenbeek, P. Moulos, R. Siersbaek, E. Megens, S. Denissov, M. Borgesen, K. J. Francoijs, S. Mandrup, et al. 2008. Genome-wide profiling of PPARgamma:RXR and RNA polymerase II occupancy reveals temporal activation of distinct metabolic pathways and changes in RXR dimer composition during adipogenesis. Genes Dev. 22 : 2953-2967.
55. Steger, D. J., G. R. Grant, M. Schupp, T. Tomaru, M. I. Lefterova, J. Schug, E. Manduchi, C. J. Stoeckert, Jr ., and M. A. Lazar. 2010. Propagation of adipogenic signals through an epigenomic transition state. Genes Dev. 24 : 1035-1044.
56. Mikkelsen, T. S., Z. Xu, X. Zhang, L. Wang, J. M. Gimble, E. S. Lander, and E. D. Rosen. 2010. Comparative epigenomic analysis of murine and human adipogenesis. Cell. 143 : 156-169.
57. Hu, E., P. Liang, and B. M. Spiegelman. 1996. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 271 : 10697-10703.
58. Steppan, C. M., S. T. Bailey, S. Bhat, E. J. Brown, R. R. Banerjee ,. M. Wright, H. R. Patel, R. S. Ahima, and M. A. Lazar. 2001. The hormone resistin links obesity to diabetes. Nature. 409 : 307-312
59. Scherer, P. E., S. Williams, M. Fogliano, G. Baldini, and H. F. Lodish. 1995. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. 270 : 26746-26749.
60. Chawla, A., and M. A. Lazar. 1994. Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival. Proc. Natl. Acad. Sci. USA. 91 : 1786-1790.
61. Tontonoz, P., E. Hu, and B. M. Spiegelman. 1994. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 79 : 1147-1156.
62. Soukas, A., N. D. Socci, B. D. Saatkamp, S. Novelli, and J. M. Friedman. 2001. Distinct transcriptional profiles of adipogenesis in vivo and in vitro. J. Biol. Chem. 276 : 34167-34174.
63. Rentsch, J., and M. Chiesi. 1996. Regulation of ob gene mRNA levels in cultured adipocytes. FEBS Lett. 379 : 55-59.
64. Van, R. L., and D. A. Roncari. 1977. Isolation of fat cell precursors from adult rat adipose tissue. Cell Tissue Res. 181 : 197-203.
65. Poznanski, W. J., I. Waheed, and R. Van. 1973. Human fat cell precursors. orphologic and metabolic differentiation in culture. Lab. Invest. 29 : 570-576.
66. Van, R. L., C. E. Bayliss, and D. A. Roncari. 1976. Cytological and enzymological characterization of adult human adipocyte precursors in culture. J. Clin. Invest. 58 : 699-704. Deleted in proof.
67. Cawthorn, W. P., E. L. Scheller, and O. A. MacDougald. 2012. Adipose tissue stem cells meet preadipocyte commitment: going back to the future. J. Lipid Res. 53 : 227-246.
68. Fasshauer, M., J. Klein, K. Ueki, K. M. Kriauciunas, M. Benito, M. F. White, and C. R. Kahn. 2000. Essential role of insulin receptor substrate-2 in insulin stimulation of Glut4 translocation and glucose uptake in brown adipocytes. J. Biol. Chem. 275 : 25494-25501.
69. Tchkonia, T., N. Giorgadze, T. Pirtskhalava, T. Thomou, M. DePonte, A. Koo, R. A. Forse, D. Chinnappan, C. Martin-Ruiz, T. von Zglinicki, et al. 2006. Fat depot-specific characteristics are retained in strains derived from single human preadipocytes. Diabetes. 55 : 2571-2578.
70. Macotela, Y., B. Emanuelli, M. A. Mori, S. Gesta, T. J. Schulz, Y. H. Tseng, and C. R. Kahn. 2012. Intrinsic differences in adipocyte precursor cells from different white fat depots. Diabetes. 61 : 1691-1699.
71. Maslowska, M. H., A. D. Sniderman, L. D. MacLean, and K. Cianflone. 1993. Regional differences in triacylglycerol synthesis in adipose tissue and in cultured preadipocytes. J. Lipid Res. 34 : 219-228.
72. Wang, Q. A., C. Tao, R. K. Gupta, and P. E. Scherer. 2013. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat. Med. 19 : 1338-1344.
73. Karastergiou, K., S. R. Smith, A. S. Greenberg, and S. K. Fried. 2012. Sex differences in human adipose tissues-the biology of pear shape. Biol. Sex Differ. 3 : 13.
74. Shi, H., R. J. Seeley, and D. J. Clegg. 2009. Sexual differences in the control of energy homeostasis. Front. Neuroendocrinol. 30 : 396-404.
75. Davis, K. E., M. D. Neinast, K. Sun, W. M. Skiles, J. D. Bills, J. A. Zehr, D. Zeve, L. D. Hahner, D. W. Cox, L. M. Gent, et al. 2013. The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis. Mol. Metab. 2 : 227-242.
76. Tchkonia, T., D. E. Morbeck, T. Von Zglinicki, J. Van Deursen, J. Lustgarten, H. Scrable, S. Khosla, M. D. Jensen, and J. L. Kirkland. 2010. Fat tissue, aging, and cellular senescence. Aging Cell. 9 : 667-684.
77. Ando, H., H. Yanagihara, Y. Hayashi, Y. Obi, S. Tsuruoka, T. Takamura, S. Kaneko, and A. Fujimura. 2005. Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology. 146 : 5631-5636.
78. Zvonic, S., A. A. Ptitsyn, S. A. Conrad, L. K. Scott, Z. E. Floyd, G. Kilroy, X. Wu, B. C. Goh, R. L. Mynatt, and J. M. Gimble. 2006. Characterization of peripheral circadian clocks in adipose tissues. Diabetes. 55 : 962-970.
79. Bray, M. S., and M. E. Young. 2007. Circadian rhythms in the development of obesity: potential role for the circadian clock within the adipocyte. Obes. Rev. 8 : 169-181.
80. Gerhart-Hines, Z., D. Feng, M. J. Emmett, L. J. Everett, E. Loro, E. R. Briggs, A. Bugge, C. Hou, C. Ferrara, P. Seale, et al. 2013. The nuclear receptor Rev-erb α controls circadian thermogenic plasticity. Nature. 503 : 410-413.
81. Hirsch, J., and P. W. Han. 1969. Cellularity of rat adipose tissue: effects of growth, starvation, and obesity. J. Lipid Res. 10 : 77-82.
82. Stiles, J. W., A. A. Francendese, and E. J. Masoro. 1975. Influence of age on size and number of fat cells in the epididymal depot. Am. J. Physiol. 229 : 1561-1568.
83. Yang, M. U., E. Presta, and P. Bjorntorp. 1990. Refeeding after fasting in rats: effects of duration of starvation and refeeding on food efficiency in diet-induced obesity. Am. J. Clin. Nutr. 51 : 970-978.
84. Spalding, K. L., E. Arner, P. O. Westermark, S. Bernard, B. A. Buchholz, O. Bergmann, L. Blomqvist, J. Hoffstedt, E. Naslund, T. Britton, et al. 2008. Dynamics of fat cell turnover in humans. Nature. 453 : 783-787.
85. Sun, K., C. M. Kusminski, and P. E. Scherer. 2011. Adipose tissue remodeling and obesity. J. Clin. Invest. 121 : 2094-2101.
86. Kim, J-Y., E. van de Wall, M. Laplante, A. Azzara, M. E. Trujillo, S. M. Hofmann, T. Schraw, J. L. Durand, H. Li, G. Li, et al. 2007. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J. Clin. Invest. 117 : 2621-2637.
87. Kusminski, C. M., W. L. Holland, K. Sun, J. Park, S. B. Spurgin, Y. Lin, G. R. Askew, J. A. Simcox, D. A. McClain, C. Li, et al. 2012. MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity. Nat. Med. 18 : 1539-1549.
88. Jo, J., O. Gavrilova, S. Pack, W. Jou, S. Mullen, A. E. Sumner, S. W. Cushman, and V. Periwal. 2009. Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLOS Comput. Biol. 5 : e1000324.
89. Joe, A. W., L. Yi, Y. Even, A. W. Vogl, and F. Rossi. 2009. Depotspecific differences in adipogenic progenitor abundance and proliferative response to high-fat diet. Stem Cells. 27 : 2563-2570.
90. Dor, Y., J. Brown, O. I. Martinez, and D. A. Melton. 2004. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature. 429 : 41-46.
91. Jopling, C., E. Sleep, M. Raya, M. Marti, A. Raya, and J. C. Izpisua Belmonte. 2010. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature. 464 : 606-609.
92. Sun, K., I. W. Asterholm, C. M. Kusminski, A. C. Bueno, Z. V. Wang, J. W. Pollard, R. A. Brekken, and P. E. Scherer. 2012. Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc. Natl. Acad. Sci. USA. 109., 5874-5879.
93. Perl, A-K. T., S. E. Wert, A. Nagy, C. G. Lobe, and J. A. Whitsett. 2002. Early restriction of peripheral and proximal cell lineages during formation of the lung. Proc. Natl. Acad. Sci. USA. 99 : 10482-10487.
94. Soriano, P. 1999. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet. 21 : 70-71.
95. Himms-Hagen, J., A. Melnyk, M. C. Zingaretti, E. Ceresi, G. Barbatelli, and S. Cinti. 2000. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am. J. Physiol. Cell Physiol. 279 : C670-C681.
96. Barbatelli, G., I. Murano, L. Madsen, Q. Hao, M. Jimenez, K. Kristiansen, J. P. Giacobino, R. De Matteis, and S. Cinti. 2010. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am. J. Physiol. Endocrinol. Metab. 298 : E1244-E1253.
97. Rosenwald, M., A. Perdikari, T. Rülicke, and C. Wolfrum. 2013. Bi-directional interconversion of brite and white adipocytes. Nat. Cell Biol. 15 : 659-667.
98. Rivers, L. E., K. M. Young, M. Rizzi, F. Jamen, K. Psachoulia, A. Wade, N. Kessaris, and W. D. Richardson. 2008. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat. Neurosci. 11 : 1392-1401.
99. Spiegelman, B. M., and J. S. Flier. 2001. Obesity and the regulation of energy balance. Cell. 104 : 531-543.
100. Kühn, R., and R. M. Torres. 2002. Cre/loxP recombination system and gene targeting. Methods Mol. Biol. 180 : 175-204.
101. He, W., Y. Barak, A. Hevener, P. Olson, D. Liao, J. Le, M. Nelson, E. Ong, J. M. Olefsky, and R. M. Evans. 2003. Adipose-specific peroxisome proliferator-activated receptor γ knockout causes insulin resistance in fat and liver but not in muscle. Proc. Natl. Acad. Sci. USA. 100 : 15712-15717.
102. Barlow, C., M. Schroeder, J. Lekstrom-Himes, H. Kylefjord, C-X. Deng, A. Wynshaw-Boris, B. M. Spiegelman, and K. G. Xanthopoulos. 1997. Targeted expression of Cre recombinase to adipose tissue of transgenic mice directs adipose-specific excision of loxP-flanked gene segments. Nucleic Acids Res. 25 : 2543-2545.
103. Ross, S. R., R. A. Graves, A. Greenstein, K. A. Platt, H. L. Shyu, B. Mellovitz, and B. M. Spiegelman. 1990. A fat-specific enhancer is the primary determinant of gene expression for adipocyte P2 in vivo. Proc. Natl. Acad. Sci. USA. 87 : 9590-9594.
104. Graves, R. A., P. Tontonoz, K. A. Platt, S. R. Ross, and B. M. Spiegelman. 1992. Identification of a fat cell enhancer: Analysis of requirements for adipose tissue-specific gene expression. J. Cell. Biochem. 49 : 219-224.
105. Lee, K. Y., S. J. Russell, S. Ussar, J. Boucher, C. Vernochet, M. A. Mori, G. Smyth, M. Rourk, C. Cederquist, E. D. Rosen, et al. 2013. Lessons on conditional gene targeting in mouse adipose tissue. Diabetes. 62 : 864-874.
106. Mullican, S. E., T. Tomaru, C. A. Gaddis, L. C. Peed, A. Sundaram, and M. A. Lazar. 2013. A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methods. Mol. Endocrinol. 27 : 127-134.
107. Makowski, L., J. B. Boord, K. Maeda, V. R. Babaev, K. T. Uysal, M. A. Morgan, R. A. Parker, J. Suttles, S. Fazio, G. S. Hotamisligil, et al. 2001. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat. Med. 7 : 699-705.
108. Urs, S., A. Harrington, L. Liaw, and D. Small. 2006. Selective expression of an aP2/fatty acid binding protein 4-Cre transgene in non-adipogenic tissues during embryonic development. Transgenic Res. 15 : 647-653.
109. Wang, Z. V., Y. Deng, Q. A. Wang, K. Sun, and P. E. Scherer. 2010. Identification and characterization of a promoter cassette conferring adipocyte-specific gene expression. Endocrinology. 151 : 2933-2939.
110. Herman, M. A., O. D. Peroni, J. Villoria, M. R. Schon, N. A. Abumrad, M. Bluher, S. Klein, and B. B. Kahn. 2012. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature. 484 : 333-338.
111. Kleiner, S., R. J. Mepani, D. Laznik, L. Ye, M. J. Jurczak, F. R. Jornayvaz, J. L. Estall, D. Chatterjee Bhowmick, G. I. Shulman, and B. M. Spiegelman. 2012. Development of insulin resistance in mice lacking PGC-1 α in adipose tissues. Proc. Natl. Acad. Sci. USA. 109 : 9635-9640
112. Zeve, D., J. Seo, J. M. Suh, D. Stenesen, W. Tang, E. D. Berglund, Y. Wan, L. J. Williams, A. Lim, M. J. Martinez, et al. 2012. Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake. Cell Metab. 15 : 492-504.
113. Tallquist, M. D., K. E. Weismann, M. Hellstrom, and P. Soriano. 2000. Early myotome specification regulates PDGFA expression and axial skeleton development. Development. 127 : 5059-5070.
114. Lepper, C., and C. M. Fan. 2010. Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells. Genesis. 48 : 424-436.
115. Ohno, H., K. Shinoda, K. Ohyama, L. Z. Sharp, and S. Kajimura. 2013. EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature. 504 : 163-167.
116. Sanchez-Gurmaches, J., C. M. Hung, C. A. Sparks, Y. Tang, H. Li, and D. A. Guertin. 2012. PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell Metab. 16 : 348-362.
117. Schulz, T. J., P. Huang, T. L. Huang, R. Xue, L. E. McDougall, K. L. Townsend, A. M. Cypess, Y. Mishina, E. Gussoni, and Y. H. Tseng. 2013. Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat. Nature. 495 : 379-383.
118. Rudnicki, M. A., P. N. Schnegelsberg, R. H. Stead, T. Braun, H-H. Arnold, and R. Jaenisch. 1993. MyoD or Myf-5 is required for the formation of skeletal muscle. Cell. 75 : 1351-1359.
119. Borycki, A-G., B. Brunk, S. Tajbakhsh, M. Buckingham, C. Chiang, and C. Emerson. 1999. Sonic hedgehog controls epaxial muscle determination through Myf5 activation. Development. 126 : 4053-4063.
120. Guerra, C., P. Navarro, A. M. Valverde, M. Arribas, J. Brüning, L. P. Kozak, C. R. Kahn, and M. Benito. 2001. Brown adipose tissuespecific insulin receptor knockout shows diabetic phenotype without insulin resistance. J. Clin. Invest. 108 : 1205-1213.
121. Imai, T., M. Jiang, P. Chambon, and D. Metzger. 2001. Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor α mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes. Proc. Natl. Acad. Sci. USA. 98 : 224-228.
122. Sassmann, A., S. Offermanns, and N. Wettschureck. 2010. Tamoxifen-inducible Cre-mediated recombination in adipocytes. Genesis. 48 : 618-625.
123. Barros, R. P., C. Gabbi, A. Morani, M. Warner, and J-Å. Gustafsson. 2009. Participation of ER α and ER β in glucose homeostasis in skeletal muscle and white adipose tissue. Am. J. Physiol. Endocrinol. Metab. 297 : E124-E133.
124. Huh, W. J., S. S. Khurana, J. H. Geahlen, K. Kohli, R. A. Waller, and J. C. Mills. 2012. Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach. Gastroenterology. 142 : 21-24.
125. Blüher, M. 2013. Importance of estrogen receptors in adipose tissue function. Mol. Metab. 2 : 130-132.
126. Reinert, R. B., J. Kantz, A. A. Misfeldt, G. Poffenberger, M. Gannon, M. Brissova, and A. C. Powers. 2012. Tamoxifen-induced Cre-loxP recombination is prolonged in pancreatic islets of adult mice. PLoS ONE. 7 : e33529.
127. Tschöp, M. H., J. R. Speakman, J. R. Arch, J. Auwerx, J. C. Brüning, L. Chan, R. H. Eckel, R. V. Farese, Jr ., J. E. Galgani, C. Hambly, et al. 2012. A guide to analysis of mouse energy metabolism. Nat. Methods. 9 : 57-63.
128. Zhang, J., Y. Zhang, T. Sun, F. Guo, S. Huang, M. Chandalia, N. Abate, D. Fan, H. B. Xin, Y. E. Chen, et al. 2013. Dietary obesityinduced Egr-1 in adipocytes facilitates energy storage via suppression of FOXC2. Sci. Rep. 3 : 1476.
129. Alekseev, A. E., S. Reyes, S. Yamada, D. M. Hodgson-Zingman, S. Sattiraju, Z. Zhu, A. Sierra, M. Gerbin, W. A. Coetzee, D. J. Goldhamer, et al. 2010. Sarcolemmal ATP-sensitive K(+) channels control energy expenditure determining body weight. Cell Metab 11 : 58-69.
130. Fischer-Posovszky, P., Q. A. Wang, I. W. Asterholm, J. M. Rutkowski, and P. E. Scherer. 2011. Targeted deletion of adipocytes by apoptosis leads to adipose tissue recruitment of alternatively activated M2 macrophages. Endocrinology. 152 : 3074-3081.
131. Guilherme, A., J. V. Virbasius, V. Puri, and M. P. Czech. 2008. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat. Rev. Mol. Cell Biol. 9 : 367-377.
132. Ouchi, N., J. L. Parker, J. J. Lugus, and K. Walsh. 2011. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11 : 85-97.
133. Lumeng, C. N., J. L. Bodzin, and A. R. Saltiel. 2007. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117 : 175-184.
134. Lumeng, C. N., J. B. DelProposto, D. J. Westcott, and A. R. Saltiel. 2008. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes. 57 : 3239-3246.
135. Sung, H. K., K. O. Doh, J. E. Son, J. G. Park, Y. Bae, S. Choi, S. M. Nelson, R. Cowling, K. Nagy, I. P. Michael, et al. 2013. Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metab. 17 : 61-72.
136. Nishimura, S., I. Manabe, M. Nagasaki, K. Eto, H. Yamashita, M. Ohsugi, M. Otsu, K. Hara, K. Ueki, S. Sugiura, et al. 2009. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med. 15 : 914-920.
137. Stolarczyk, E., C. T. Vong, E. Perucha, I. Jackson, M. A. Cawthorne, E. T. Wargent, N. Powell, J. B. Canavan, G. M. Lord, and J. K. Howard. 2013. Improved insulin sensitivity despite increased visceral adiposity in mice deficient for the immune cell transcription factor T-bet. Cell Metab. 17 : 520-533.
138. Feng, D., Y. Tang, H. Kwon, H. Zong, M. Hawkins, R. N. Kitsis, and J. E. Pessin. 2011. High-fat diet-induced adipocyte cell death occurs through a cyclophilin D intrinsic signaling pathway independent of adipose tissue inflammation. Diabetes. 60 : 2134-2143.
139. Sun, K., N. Halberg, M. Khan, U. J. Magalang, and P. E. Scherer. 2013. Selective inhibition of hypoxia-inducible factor 1alpha ameliorates adipose tissue dysfunction. Mol. Cell. Biol. 33 : 904-917.
140. Semenza, G. L. 2000. Surviving ischemia: adaptive responses mediated by hypoxia-inducible factor 1. J. Clin. Invest. 106 : 809-812.
141. Ozcan, U., Q. Cao, E. Yilmaz, A-H. Lee, N. N. Iwakoshi, E. Ozdelen, G. Tuncman, C. Gorgun, L. H. Glimcher, and G. S. Hotamisligil. 2004. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 306 : 457-461.
142. Hosogai, N., A. Fukuhara, K. Oshima, Y. Miyata, S. Tanaka, K. Segawa, S. Furukawa, Y. Tochino, R. Komuro, M. Matsuda, et al. 2007. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes. 56 : 901-911.
143. Huang, G., and D. S. Greenspan. 2012. ECM roles in the function of metabolic tissues. Trends Endocrinol. Metab. 23 : 16-22.
144. Khan, T., E. S. Muise, P. Iyengar, Z. V. Wang, M. Chandalia, N. Abate, B. B. Zhang, P. Bonaldo, S. Chua, and P. E. Scherer. 2009. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29 : 1575-1591.
145. Divoux, A., J. Tordjman, D. Lacasa, N. Veyrie, D. Hugol, A. Aissat ,A. Basdevant, M. Guerre-Millo, C. Poitou, J. D. Zucker, et al. 2010. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes. 59 : 2817-2825.
146. Jonker, J. W., J. M. Suh, A. R. Atkins, M. Ahmadian, P. Li, J. Whyte, M. He, H. Juguilon, Y. Q. Yin, C. T. Phillips, et al. 2012. A PPARgamma-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis. Nature. 485 : 391-394.
147. Halberg, N., T. Khan, M. E. Trujillo, I. Wernstedt-Asterholm, A. D. Attie, S. Sherwani, Z. V. Wang, S. Landskroner-Eiger, S. Dineen, U. J. Magalang, et al. 2009. Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Mol. Cell. Biol. 29 : 4467-4483.
148. Miki, T., K. Minami, L. Zhang, M. Morita, T. Gonoi, T. Shiuchi, Y. Minokoshi, J-M. Renaud, and S. Seino. 2002. ATP-sensitive potassium channels participate in glucose uptake in skeletal muscle and adipose tissue. Am. J. Physiol. Endocrinol. Metab. 283 :E1178-E1184.
149. Mittendorfer, B. 2005. Insulin resistance: sex matters. Curr. Opin. Clin. Nutr. Metab. Care. 8 : 367-372.
150. Abel, E. D., O. Peroni, J. K. Kim, Y. B. Kim, O. Boss, E. Hadro, T. Minnemann, G. I. Shulman, and B. B. Kahn. 2001. Adiposeselective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 409 : 729-733.
151. Voshol, P. J., M. C. Jong, V. E. H. Dahlmans, D. Kratky, S. Levak-Frank, R. Zechner, J. A. Romijn, and L. M. Havekes. 2001. In muscle-specific lipoprotein lipase-overexpressing mice, muscle triglyceride content is increased without inhibition of insulin-stimulated whole-body and muscle-specific glucose uptake. Diabetes. 50 : 2585-2590.
152. Jones, J. R., C. Barrick, K-A. Kim, J. Lindner, B. Blondeau, Y. Fujimoto, M. Shiota, R. A. Kesterson, B. B. Kahn, and M. A. Magnuson. 2005. Deletion of PPAR γ in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance. Proc. Natl. Acad. Sci. USA. 102 : 6207-6212.
153. Arkan, M. C., A. L. Hevener, F. R. Greten, S. Maeda, Z-W. Li, J. M. Long, A. Wynshaw-Boris, G. Poli, J. Olefsky, and M. Karin. 2005. IKK-β links inflammation to obesity-induced insulin resistance. Nat. Med. 11 : 191-198.
154. Guo, H., D. Jin, Y. Zhang, W. Wright, M. Bazuine, D. A. Brockman, D. A. Bernlohr, and X. Chen. 2010. Lipocalin-2 deficiency impairs thermogenesis and potentiates diet-induced insulin resistance in mice. Diabetes. 59 : 1376-1385.
155. Macotela, Y., J. Boucher, T. T. Tran, and C. R. Kahn. 2009. Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism. Diabetes. 58 : 803-812.
156. Le, H. T., S. Ponniah, and C. J. Pallen. 2004. Insulin signaling and glucose homeostasis in mice lacking protein tyrosine phosphatase α. Biochem. Biophys. Res. Commun. 314 : 321-329.
157. Yu, X., N. Shen, M. L. Zhang, F. Y. Pan, C. Wang, W. P. Jia, C. Liu, Q. Gao, X. Gao, B. Xue, et al. 2011. Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice. EMBO J. 30 : 3754-3765.
158. Sutanto, M. M., K. K. Ferguson, H. Sakuma, H. Ye, M. J. Brady, and R. N. Cohen. 2010. The silencing mediator of retinoid and thyroid hormone receptors (SMRT) regulates adipose tissue accumulation and adipocyte insulin sensitivity in vivo. J. Biol. Chem. 285 : 18485-18495.
159. Unger, R. H., and A. D. Cherrington. 2012. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J. Clin. Invest. 122 : 4-12.
160. Duncan, R. E., M. Ahmadian, K. Jaworski, E. Sarkadi-Nagy, and H. S. Sul. 2007. Regulation of lipolysis in adipocytes. Annu. Rev. Nutr. 27 : 79-101.
161. Large, V., S. Reynisdottir, D. Langin, K. Fredby, M. Klannemark, C. Holm, and P. Arner. 1999. Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J. Lipid Res. 40 : 2059-2066.
162. Reynisdottir, S., D. Langin, K. Carlstrom, C. Holm, S. Rossner, and P. Arner. 1995. Effects of weight reduction on the regulationof lipolysis in adipocytes of women with upper-body obesity. Clin. Sci. (Lond). 89: 421-429.
163. Wang, S. P., N. Laurin, J. Himms-Hagen, M. A. Rudnicki, E. Levy, M. F. Robert, L. Pan, L. Oligny, and G. A. Mitchell. 2001. The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes. Res. 9 : 119-128.
164. Holm, C. 2003. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem. Soc. Trans. 31 : 1120-1124.
165. Vaughan, M., J. E. Berger, and D. Steinberg. 1964. Hormonesensitive lipase and monoglyceride lipase activities in adipose tissue. J. Biol. Chem. 239 : 401-409.
166. Villena, J. A., S. Roy, E. Sarkadi-Nagy, K. H. Kim, and H. S. Sul. 2004. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J. Biol. Chem. 279 : 47066-47075.
167. Zimmermann, R., J. G. Strauss, G. Haemmerle, G. Schoiswohl, R. Birner-Gruenberger, M. Riederer, A. Lass, G. Neuberger, F. Eisenhaber, A. Hermetter, et al. 2004. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science. 306 : 1383-1386.
168. Haemmerle, G., R. Zimmermann, M. Hayn, C. Theussl, G. Waeg, E. Wagner, W. Sattler, T. M. Magin, E. F. Wagner, and R. Zechner. 2002. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J. Biol Chem. 277 : 4806-4815.
169. Lampidonis, A. D., E. Rogdakis, G. E. Voutsinas, and D. J. Stravopodis. 2011. The resurgence of hormone-sensitive lipase (HSL) in mammalian lipolysis. Gene. 477 : 1-11.
170. Haemmerle, G., A. Lass, R. Zimmermann, G. Gorkiewicz, C. Meyer, J. Rozman, G. Heldmaier, R. Maier, C. Theussl, S. Eder, et al. 2006. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science. 312 : 734-737.
171. Ahmadian, M., M. J. Abbott, T. Tang, C. S. Hudak, Y. Kim, M. Bruss, M. K. Hellerstein, H. Y. Lee, V. T. Samuel, G. I. Shulman, et al. 2011. Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype. Cell Metab. 13 : 739-748.
172. Lass, A., R. Zimmermann, G. Haemmerle, M. Riederer, G. Schoiswohl, M. Schweiger, P. Kienesberger, J. G. Strauss, G. Gorkiewicz, and R. Zechner. 2006. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab. 3 : 309-319.
173. Soni, K. G., R. Lehner, P. Metalnikov, P. O'Donnell, M. Semache, W. Gao, K. Ashman, A. V. Pshezhetsky, and G. A. Mitchell. 2004. Carboxylesterase 3 (EC 3.1.1.1) is a major adipocyte lipase. J. Biol. Chem. 279 : 40683-40689.
174. Jenkins, C. M., D. J. Mancuso, W. Yan, H. F. Sims, B. Gibson, and R. W. Gross. 2004. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J. Biol. Chem. 279 : 48968-48975.
175. Tornqvist, H., and P. Belfrage. 1976. Purification and some properties of a monoacylglycerol-hydrolyzing enzyme of rat adipose tissue. J. Biol. Chem. 251 : 813-819.
176. Brasaemle, D. L., B. Rubin, I. A. Harten, J. Gruia-Gray, A. R. Kimmel, and C. Londos. 2000. Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. J. Biol. Chem. 275 : 38486-38493.
177. Souza, S. C., K. V. Muliro, L. Liscum, P. Lien, M. T. Yamamoto, J. E. Schaffer, G. E. Dallal, X. Wang, F. B. Kraemer, M. Obin, et al. 2002. Modulation of hormone-sensitive lipase and protein kinase A-mediated lipolysis by perilipin A in an adenoviral reconstituted system. J. Biol. Chem. 277 : 8267-8272.
178. Sztalryd, C., G. Xu, H. Dorward, J. T. Tansey, J. A. Contreras, A. R. Kimmel, and C. Londos. 2003. Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation. J. Cell Biol. 161 : 1093-1103.
179. Tansey, J. T., A. M. Huml, R. Vogt, K. E. Davis, J. M. Jones, K. A. Fraser, D. L. Brasaemle, A. R. Kimmel, and C. Londos. 2003. Functional studies on native and mutated forms of perilipins. A role in protein kinase A-mediated lipolysis of triacylglycerols. J. Biol. Chem. 278 : 8401-8406.
180. Miyoshi, H., S. C. Souza, H. H. Zhang, K. J. Strissel, M. A. Christoffolete, J. Kovsan, A. Rudich, F. B. Kraemer, A. C. Bianco, M. S. Obin, et al. 2006. Perilipin promotes hormone-sensitive lipase-mediated adipocyte lipolysis via phosphorylation-dependent and-independent mechanisms. J. Biol. Chem. 281 : 15837-15844.
181. Brasaemle, D. L. 2010. Lipolysis control: the plot thickens. Cell Metab. 11 : 173-174.
182. Marcinkiewicz, A., D. Gauthier, A. Garcia, and D. L. Brasaemle. 2006. The phosphorylation of serine 492 of perilipin a directs lipid droplet fragmentation and dispersion. J. Biol. Chem. 281 : 11901-11909.
183. Moore, H. P., R. B. Silver, E. P. Mottillo, D. A. Bernlohr, and J. G. Granneman. 2005. Perilipin targets a novel pool of lipid droplets for lipolytic attack by hormone-sensitive lipase. J. Biol. Chem. 280 : 43109-43120.
184. Rohm, M., A. Sommerfeld, D. Strzoda, A. Jones, T. P. Sijmonsma, G. Rudofsky, C. Wolfrum, C. Sticht, N. Gretz, M. Zeyda, et al. 2013. Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue. Cell Metab. 17 : 575-585.
185. Mennes, E., C. M. Dungan, S. Frendo-Cumbo, D. L. Williamson, and D. C. Wright. Aging-associated reductions in lipolytic and mitochondrial proteins in mouse adipose tissue are not rescued by metformin treatment. J. Gerontol. A Biol. Sci. Med. Sci. Epub ahead of print. October 14, 2013; doi:10.1093/gerona/ glt156.
186. Grujic, D., V. S. Susulic, M-E. Harper, J. Himms-Hagen, B. A. Cunningham, B. E. Corkey, and B. B. Lowell. 1997. Beta3-adrenergic receptors on white and brown adipocytes mediate beta3-selective agonist-induced effects on energy expenditure, insulin secretion, and food intake. A study using transgenic and gene knockout mice. J. Biol. Chem. 272 : 17686-17693.
187. Asterholm, I. W., D. I. Mundy, J. Weng, R. G. Anderson, and P. E. Scherer. 2012. Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1. Cell Metab. 15 : 171-185.
188. Kusminski, C. M., and P. E. Scherer. 2012. Mitochondrial dysfunction in white adipose tissue. Trends Endocrinol. Metab. 23 : 435-443.
189. Bartelt, A., O. T. Bruns, R. Reimer, H. Hohenberg, H. Ittrich, K. Peldschus, M. G. Kaul, U. I. Tromsdorf, H. Weller, C. Waurisch, et al. 2011. Brown adipose tissue activity controls triglyceride clearance. Nat. Med. 17 : 200-205.
190. Wei, X., D. Wang, Y. Yang, M. Xia, D. Li, G. Li, Y. Zhu, Y. Xiao, and W. Ling. 2011. Cyanidin-3-O-β-glucoside improves obesity and triglyceride metabolism in KK-Ay mice by regulating lipoprotein lipase activity. J. Sci. Food Agric. 91 : 1006-1013.
191. Khanade, J. M., and M. C. Nath. 1961. Lipogenesis in adipose tissue of rats fed different diets. Am. J. Physiol. 201 : 1041-1043.
192. Lodhi, I. J., L. Yin, A. P. Jensen-Urstad, K. Funai, T. Coleman, J. H. Baird, M. K. El Ramahi, B. Razani, H. Song, F. Fu-Hsu, et al. 2012. Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPAR γ activation to decrease diet-induced obesity. Cell Metab. 16 : 189-201.
193. Marcelino, H., C. Veyrat-Durebex, S. Summermatter, D. Sarafian, J. Miles-Chan, D. Arsenijevic, F. Zani, J-P. Montani, J. Seydoux, G. Solinas, et al. 2013. A role for adipose tissue de novo lipogenesis in glucose homeostasis during catch-up growth a Randle cycle favoring fat storage. Diabetes. 62 : 362-372.
194. Strawford, A., F. Antelo, M. Christiansen, and M. K. Hellerstein. 2004. Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O. Am. J. Physiol. Endocrinol. Metab. 286 : E577-E588.
195. Acheson, K. J., J. P. Flatt, and E. Jequier. 1982. Glycogen synthesis versus lipogenesis after a 500 gram carbohydrate meal in man. Metabolism. 31 : 1234-1240.
196. Hellerstein, M. K. 1999. De novo lipogenesis in humans: metabolic and regulatory aspects. Eur. J. Clin. Nutr. 53 ( Suppl 1 ): S53-S65.
197. Hellerstein, M. K., J. M. Schwarz, and R. A. Neese. 1996. Regulation of hepatic de novo lipogenesis in humans. Annu. Rev. Nutr. 16 : 523-557.
198. Hoffstedt, J., D. Förster, and P. Löfgren. 2007. Impaired subcutaneous adipocyte lipogenesis is associated with systemic insulin resistance and increased apolipoprotein B/AI ratio in men and women. J. Intern. Med. 262 : 131-139.
199. Ranganathan, G., R. Unal, I. Pokrovskaya, A. Yao-Borengasser, B. Phanavanh, B. Lecka-Czernik, N. Rasouli, and P. A. Kern. 2006. The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment. J. Lipid Res. 47 : 2444-2450.
200. Scherer, T., J. O'Hare, K. Diggs-Andrews, M. Schweiger, B. Cheng, C. Lindtner, E. Zielinski, P. Vempati, K. Su, S. Dighe, et al. 2011. Brain insulin controls adipose tissue lipolysis and lipogenesis. Cell Metab. 13 : 183-194.
201. Buettner, C., E. D. Muse, A. Cheng, L. Chen, T. Scherer, A. Pocai, K. Su, B. Cheng, X. Li, J. Harvey-White, et al. 2008. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat. Med. 14 : 667-675.
202. Jiang, L., Q. Wang, Y. Yu, F. Zhao, P. Huang, R. Zeng, R. Z. Qi, W. Li, and Y. Liu. 2009. Leptin contributes to the adaptive responses of mice to high-fat diet intake through suppressing the lipogenic pathway. PLoS ONE. 4 : e6884.
203. Wang, Q., L. Jiang, J. Wang, S. Li, Y. Yu, J. You, R. Zeng, X. Gao, L. Rui, W. Li, et al. 2009. Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice. Hepatology. 49 : 1166-1175.
204. Klöting, N., M. Fasshauer, A. Dietrich, P. Kovacs, M. R. Schön, M. Kern, M. Stümvoll, and M. Bluher. 2010. Insulin-sensitive obesity. Am. J. Physiol. Endocrinol. Metab. 299 : E506-E515.
205. Nedergaard, J., T. Bengtsson, and B. Cannon. 2011. New powers of brown fat: fighting the metabolic syndrome. Cell Metab. 13 : 238-240.
206. Virtue, S., and A. Vidal-Puig. 2013. Assessment of brown adipose tissue function. Front. Physiol. 4 : 128.
207. Deleted in proof. 210. Harms, M., and P. Seale. 2013. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 19 : 1252-1263.
208. Whittle, A. J., S. Carobbio, L. Martins, M. Slawik, E. Hondares, M. J. Vázquez, D. Morgan, R. I. Csikasz, R. Gallego, S. Rodriguez-Cuenca, et al. 2012. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell. 149 : 871-885.
209. Taha, M. F., M. R. Valojerdi, and S. J. Mowla. 2006. Effect of bone morphogenetic protein-4 (BMP-4) on adipocyte differentiation from mouse embryonic stem cells. Anat. Histol. Embryol. 35 : 271-278.
210. Tseng, Y. H., E. Kokkotou, T. J. Schulz, T. L. Huang, J. N. Winnay, C. M. Taniguchi, T. T. Tran, R. Suzuki, D. O. Espinoza, Y. Yamamoto, et al. 2008. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature. 454 : 1000-1004.
211. Tang, Q. Q., T. C. Otto, and M. D. Lane. 2004. Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc. Natl. Acad. Sci. USA. 101 : 9607-9611.
212. Green, H., and O. Kehinde. 1979. Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. J. Cell. Physiol. 101 : 169-171.
213. Kajimura, S., P. Seale, K. Kubota, E. Lunsford, J. V. Frangioni, S. P. Gygi, and B. M. Spiegelman. 2009. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature. 460 : 1154-1158.
214. Kang, S., P. Akerblad, R. Kiviranta, R. K. Gupta, S. Kajimura, M. J. Griffin, J. Min, R. Baron, and E. D. Rosen. 2012. Regulation of early adipose commitment by Zfp521. PLoS Biol. 10 : e1001433.
215. Van, R. L., and D. A. Roncari. 1982. Complete differentiation in vivo of implanted cultured adipocyte precursors from adult rats. Cell Tissue Res. 225 : 557-566.
216. Asterholm, I. W., N. Halberg, and P. E. Scherer. 2007. Mouse models of lipodystrophy key reagents for the understanding of the metabolic syndrome. Drug Discov. Today Dis. Models. 4 : 17-24.
217. Shepherd, P. R., L. Gnudi, E. Tozzo, H. Yang, F. Leach, and B. B. Kahn. 1993. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. J. Biol. Chem. 268 : 22243-22246.
218. Keller, C., M. S. Hansen, C. M. Coffin, and M. R. Capecchi. 2004. Pax3: Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin. Genes Dev. 18 : 2608-2613.
219. Lepper, C., S. J. Conway, and C-M. Fan. 2009. Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements. Nature. 460 : 627-631.