The Complexity of Adipose Tissue

  • Katie M. Troike
  • Kevin Y. Lee
  • Edward O. List
  • Darlene E. BerrymanEmail author


Excess adipose tissue, or obesity, represents one of the most significant public health problems of our time. Obesity and its associated metabolic complications have necessitated the search for alternative therapeutic options aimed at reducing adiposity. However, our understanding of adipose tissue (AT) continues to evolve, revealing a more dynamic and elaborate tissue than once thought and complicating the search for therapeutic targets. A more recent appreciation of the distinct types of adipocytes, depot differences, cellular and extracellular matrix complexity, and the endocrine properties of AT is worthy of discussion as they all contribute to the key homeostatic role played by this tissue. This chapter will introduce these concepts and describe how various AT characteristics are altered in a lipodystrophic and obese state.


White adipose tissue Brown adipose tissue Beige adipocytes Depot-specific differences Lipodystrophy Adipokine Obesity 


  1. Abramson, E. A., & Arky, R. A. (1968). Acute antilipolytic effects of ethyl alcohol and acetate in man. The Journal of Laboratory and Clinical Medicine, 72(1), 105–117.PubMedGoogle Scholar
  2. Antuna-Puente, B., Boutet, E., Vigouroux, C., Lascols, O., Slama, L., Caron-Debarle, M., Khallouf, E., Levy-Marchal, C., Capeau, J., Bastard, J. P., & Magre, J. (2010). Higher adiponectin levels in patients with Berardinelli-Seip congenital lipodystrophy due to seipin as compared with 1-acylglycerol-3-phosphate-o-acyltransferase-2 deficiency. The Journal of Clinical Endocrinology and Metabolism, 95(3), 1463–1468. Scholar
  3. Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., Kuriyama, H., Nishida, M., Yamashita, S., Okubo, K., Matsubara, K., Muraguchi, M., Ohmoto, Y., Funahashi, T., & Matsuzawa, Y. (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochemical and Biophysical Research Communications, 257(1), 79–83.CrossRefPubMedGoogle Scholar
  4. Bamshad, M., Song, C. K., & Bartness, T. J. (1999). CNS origins of the sympathetic nervous system outflow to brown adipose tissue. The American Journal of Physiology, 276(6 Pt 2), R1569–R1578.PubMedGoogle Scholar
  5. Baptiste, C. G., Battista, M. C., Trottier, A., & Baillargeon, J. P. (2010). Insulin and hyperandrogenism in women with polycystic ovary syndrome. The Journal of Steroid Biochemistry and Molecular Biology, 122(1–3), 42–52. Scholar
  6. Berryman, D., Householder, L., Lesende, V., List, E., & Kopchick, J. J. (2015). Living large: What mouse models reveal about growth hormone. In N. A. Berger (Ed.), Murine models, energy, balance, and cancer (pp. 65–95). New York: Springer.CrossRefGoogle Scholar
  7. Berryman, D. E., List, E. O., Sackmann-Sala, L., Lubbers, E., Munn, R., & Kopchick, J. J. (2011). Growth hormone and adipose tissue: Beyond the adipocyte. Growth Hormone & IGF Research, 21(3), 113–123. Scholar
  8. Bindlish, S., Presswala, L. S., & Schwartz, F. (2015). Lipodystrophy: Syndrome of severe insulin resistance. Postgraduate Medicine, 127(5), 511–516. Scholar
  9. Bjorntorp, P. (1990). “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis, 10(4), 493–496.CrossRefPubMedGoogle Scholar
  10. Bluher, M., Patti, M. E., Gesta, S., Kahn, B. B., & Kahn, C. R. (2004). Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression. The Journal of Biological Chemistry, 279(30), 31891–31901. Scholar
  11. Brestoff, J. R., & Artis, D. (2015). Immune regulation of metabolic homeostasis in health and disease. Cell, 161(1), 146–160. Scholar
  12. Carroll, J. F., Chiapa, A. L., Rodriquez, M., Phelps, D. R., Cardarelli, K. M., Vishwanatha, J. K., Bae, S., & Cardarelli, R. (2008). Visceral fat, waist circumference, and BMI: Impact of race/ethnicity. Obesity, 16(3), 600–607. Scholar
  13. Chang, Y. H., Chang, D. M., Lin, K. C., Shin, S. J., & Lee, Y. J. (2011). Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: A meta-analysis and systemic review. Diabetes/Metabolism Research and Reviews, 27(6), 515–527. Scholar
  14. Chau, Y. Y., Bandiera, R., Serrels, A., Martinez-Estrada, O. M., Qing, W., Lee, M., Slight, J., Thornburn, A., Berry, R., McHaffie, S., Stimson, R. H., Walker, B. R., Chapuli, R. M., Schedl, A., & Hastie, N. (2014). Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source. Nature Cell Biology, 16(4), 367–375. Scholar
  15. Chen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., Moore, K. J., Breitbart, R. E., Duyk, G. M., Tepper, R. I., & Morgenstern, J. P. (1996). Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell, 84(3), 491–495.CrossRefPubMedGoogle Scholar
  16. Choe, S. S., Huh, J. Y., Hwang, I. J., Kim, J. I., & Kim, J. B. (2016). Adipose tissue remodeling: Its role in energy metabolism and metabolic disorders. Frontiers in Endocrinology (Lausanne), 7, 30. Scholar
  17. Chusyd, D. E., Wang, D., Huffman, D. M., & Nagy, T. R. (2016). Relationships between rodent white adipose fat pads and human white adipose fat depots. Frontiers in Nutrition, 3, 10. Scholar
  18. Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A. S., & Obin, M. S. (2005). Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. Journal of Lipid Research, 46(11), 2347–2355.CrossRefPubMedGoogle Scholar
  19. Clement, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J. M., Basdevant, A., Bougneres, P., Lebouc, Y., Froguel, P., & Guy-Grand, B. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature, 392(6674), 398–401. Scholar
  20. Crewe, C., An, Y. A., & Scherer, P. E. (2017). The ominous triad of adipose tissue dysfunction: Inflammation, fibrosis, and impaired angiogenesis. The Journal of Clinical Investigation, 127(1), 74–82. Scholar
  21. Curat, C. A., Wegner, V., Sengenes, C., Miranville, A., Tonus, C., Busse, R., & Bouloumie, A. (2006). Macrophages in human visceral adipose tissue: Increased accumulation in obesity and a source of resistin and visfatin. Diabetologia, 49(4), 744–747. Scholar
  22. Cuthbertson, D. J., Steele, T., Wilding, J. P., Halford, J. C., Harrold, J. A., Hamer, M., & Karpe, F. (2017). What have human experimental overfeeding studies taught us about adipose tissue expansion and susceptibility to obesity and metabolic complications? International Journal of Obesity.
  23. Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y. H., Doria, A., Kolodny, G. M., & Kahn, C. R. (2009). Identification and importance of brown adipose tissue in adult humans. The New England Journal of Medicine, 360(15), 1509–1517.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Cypess, A. M., White, A. P., Vernochet, C., Schulz, T. J., Xue, R., Sass, C. A., Huang, T. L., Roberts-Toler, C., Weiner, L. S., Sze, C., Chacko, A. T., Deschamps, L. N., Herder, L. M., Truchan, N., Glasgow, A. L., Holman, A. R., Gavrila, A., Hasselgren, P. O., Mori, M. A., Molla, M., & Tseng, Y. H. (2013). Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nature Medicine, 19(5), 635–639. Scholar
  25. D'Eon, T. M., Souza, S. C., Aronovitz, M., Obin, M. S., Fried, S. K., & Greenberg, A. S. (2005). Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. The Journal of Biological Chemistry, 280(43), 35983–35991. Scholar
  26. de Souza Batista, C. M., Yang, R. Z., Lee, M. J., Glynn, N. M., Yu, D. Z., Pray, J., Ndubuizu, K., Patil, S., Schwartz, A., Kligman, M., Fried, S. K., Gong, D. W., Shuldiner, A. R., Pollin, T. I., & McLenithan, J. C. (2007). Omentin plasma levels and gene expression are decreased in obesity. Diabetes, 56(6), 1655–1661. Scholar
  27. Denis, G. V., & Obin, M. S. (2013). Metabolically healthy obesity: Origins and implications. Molecular Aspects of Medicine, 34(1), 59–70. Scholar
  28. DiGirolamo, M., Fine, J. B., Tagra, K., & Rossmanith, R. (1998). Qualitative regional differences in adipose tissue growth and cellularity in male Wistar rats fed ad libitum. The American Journal of Physiology, 274(5 Pt 2), R1460–R1467.PubMedGoogle Scholar
  29. Duncan, R. E., Ahmadian, M., Jaworski, K., Sarkadi-Nagy, E., & Sul, H. S. (2007). Regulation of lipolysis in adipocytes. Annual Review of Nutrition, 27, 79–101. Scholar
  30. Enerback, S., Jacobsson, A., Simpson, E. M., Guerra, C., Yamashita, H., Harper, M. E., & Kozak, L. P. (1997). Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature, 387(6628), 90–94. Scholar
  31. Fan, W., Yanase, T., Nomura, M., Okabe, T., Goto, K., Sato, T., Kawano, H., Kato, S., & Nawata, H. (2005). Androgen receptor null male mice develop late-onset obesity caused by decreased energy expenditure and lipolytic activity but show normal insulin sensitivity with high adiponectin secretion. Diabetes, 54(4), 1000–1008.CrossRefPubMedGoogle Scholar
  32. Feldmann, H. M., Golozoubova, V., Cannon, B., & Nedergaard, J. (2009). UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metabolism, 9(2), 203–209. Scholar
  33. Fiorenza, C. G., Chou, S. H., & Mantzoros, C. S. (2011). Lipodystrophy: Pathophysiology and advances in treatment. Nature Reviews Endocrinology, 7(3), 137–150. Scholar
  34. Frederich, R. C., Hamann, A., Anderson, S., Lollmann, B., Lowell, B. B., & Flier, J. S. (1995). Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action. Nature Medicine, 1(12), 1311–1314.CrossRefPubMedGoogle Scholar
  35. Garg, A. (2006). Adipose tissue dysfunction in obesity and lipodystrophy. Clinical Cornerstone, 8(Suppl 4), S7–S13.CrossRefPubMedGoogle Scholar
  36. Garg, A. (2011). Clinical review#: Lipodystrophies: Genetic and acquired body fat disorders. The Journal of Clinical Endocrinology and Metabolism, 96(11), 3313–3325. Scholar
  37. Geer, E. B., & Shen, W. (2009). Gender differences in insulin resistance, body composition, and energy balance. Gender Medicine, 6(Suppl 1), 60–75. Scholar
  38. Gesta, S., Bluher, M., Yamamoto, Y., Norris, A. W., Berndt, J., Kralisch, S., Boucher, J., Lewis, C., & Kahn, C. R. (2006). Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proceedings of the National Academy of Sciences of the United States of America, 103(17), 6676–6681.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Giralt, M., & Villarroya, F. (2013). White, brown, beige/brite: Different adipose cells for different functions? Endocrinology, 154(9), 2992–3000. Scholar
  40. Gliemann, J., & Vinten, J. (1974). Lipogenesis and insulin sensitivity of single fat cells. The Journal of Physiology, 236(3), 499–516.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Grove, K. L., Fried, S. K., Greenberg, A. S., Xiao, X. Q., & Clegg, D. J. (2010). A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice. International Journal of Obesity, 34(6), 989–1000. Scholar
  42. Hana, V., Silha, J. V., Justova, V., Lacinova, Z., Stepan, J. J., & Murphy, L. J. (2004). The effects of GH replacement in adult GH-deficient patients: Changes in body composition without concomitant changes in the adipokines and insulin resistance. Clinical Endocrinology, 60(4), 442–450.CrossRefPubMedGoogle Scholar
  43. Haque, W. A., Shimomura, I., Matsuzawa, Y., & Garg, A. (2002). Serum adiponectin and leptin levels in patients with lipodystrophies. The Journal of Clinical Endocrinology and Metabolism, 87(5), 2395. Scholar
  44. Hara, K., Horikoshi, M., Yamauchi, T., Yago, H., Miyazaki, O., Ebinuma, H., Imai, Y., Nagai, R., & Kadowaki, T. (2006). Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care, 29(6), 1357–1362.CrossRefPubMedGoogle Scholar
  45. Harman-Boehm, I., Bluher, M., Redel, H., Sion-Vardy, N., Ovadia, S., Avinoach, E., Shai, I., Kloting, N., Stumvoll, M., Bashan, N., & Rudich, A. (2007). Macrophage infiltration into omental versus subcutaneous fat across different populations: Effect of regional adiposity and the comorbidities of obesity. The Journal of Clinical Endocrinology and Metabolism, 92(6), 2240–2247. Scholar
  46. Heine, P. A., Taylor, J. A., Iwamoto, G. A., Lubahn, D. B., & Cooke, P. S. (2000). Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proceedings of the National Academy of Sciences of the United States of America, 97(23), 12729–12734. Scholar
  47. Hirose, H., Yamamoto, Y., Seino-Yoshihara, Y., Kawabe, H., & Saito, I. (2010). Serum high-molecular-weight adiponectin as a marker for the evaluation and care of subjects with metabolic syndrome and related disorders. Journal of Atherosclerosis and Thrombosis, 17(12), 1201–1211.CrossRefPubMedGoogle Scholar
  48. Horton, T. J., Dow, S., Armstrong, M., & Donahoo, W. T. (2009). Greater systemic lipolysis in women compared with men during moderate-dose infusion of epinephrine and/or norepinephrine. Journal of Applied Physiology, 107(1), 200–210. Scholar
  49. Ibrahim, M. M. (2010). Subcutaneous and visceral adipose tissue: Structural and functional differences. Obesity Reviews: An Official Journal of the International Association for the Study of Obesity, 11(1), 11–18. Scholar
  50. Jeffery, E., Wing, A., Holtrup, B., Sebo, Z., Kaplan, J. L., Saavedra-Pena, R., Church, C. D., Colman, L., Berry, R., & Rodeheffer, M. S. (2016). The adipose tissue microenvironment regulates depot-specific adipogenesis in obesity. Cell Metabolism, 24(1), 142–150. Scholar
  51. Kajimura, S., Spiegelman, B. M., & Seale, P. (2015). Brown and beige fat: Physiological roles beyond heat generation. Cell Metabolism, 22(4), 546–559. Scholar
  52. Katzmarzyk, P. T., Bray, G. A., Greenway, F. L., Johnson, W. D., Newton, R. L., Jr., Ravussin, E., Ryan, D. H., Smith, S. R., & Bouchard, C. (2010). Racial differences in abdominal depot-specific adiposity in white and African American adults. The American Journal of Clinical Nutrition, 91(1), 7–15. Scholar
  53. Kersten, S. (2001). Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Reports, 2(4), 282–286. Scholar
  54. Khan, T., Muise, E. S., Iyengar, P., Wang, Z. V., Chandalia, M., Abate, N., Zhang, B. B., Bonaldo, P., Chua, S., & Scherer, P. E. (2009). Metabolic dysregulation and adipose tissue fibrosis: Role of collagen VI. Molecular and Cellular Biology, 29(6), 1575–1591.CrossRefPubMedGoogle Scholar
  55. Kusminski, C. M., Bickel, P. E., & Scherer, P. E. (2016). Targeting adipose tissue in the treatment of obesity-associated diabetes. Nature Reviews Drug Discovery.
  56. Kwok, K. H., Lam, K. S., & Xu, A. (2016). Heterogeneity of white adipose tissue: Molecular basis and clinical implications. Experimental & Molecular Medicine, 48, e215. Scholar
  57. Lee, K. Y., Yamamoto, Y., Boucher, J., Winnay, J. N., Gesta, S., Cobb, J., Bluher, M., & Kahn, C. R. (2013a). Shox2 is a molecular determinant of depot-specific adipocyte function. Proceedings of the National Academy of Sciences of the United States of America, 110(28), 11409–11414. Scholar
  58. Lee, M. J., Wu, Y., & Fried, S. K. (2013b). Adipose tissue heterogeneity: Implication of depot differences in adipose tissue for obesity complications. Molecular Aspects of Medicine, 34(1), 1–11. Scholar
  59. Lee, Y. H., Kim, S. N., Kwon, H. J., & Granneman, J. G. (2017). Metabolic heterogeneity of activated beige/brite adipocytes in inguinal adipose tissue. Scientific Reports, 7, 39794. Scholar
  60. Lidell, M. E., Betz, M. J., Dahlqvist Leinhard, O., Heglind, M., Elander, L., Slawik, M., Mussack, T., Nilsson, D., Romu, T., Nuutila, P., Virtanen, K. A., Beuschlein, F., Persson, A., Borga, M., & Enerback, S. (2013). Evidence for two types of brown adipose tissue in humans. Nature Medicine, 19(5), 631–634. Scholar
  61. Lofgren, P., Hoffstedt, J., Ryden, M., Thorne, A., Holm, C., Wahrenberg, H., & Arner, P. (2002). Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. The Journal of Clinical Endocrinology and Metabolism, 87(2), 764–771. Scholar
  62. Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007). Obesity induces a phenotypic switch in adipose tissue macrophage polarization. The Journal of Clinical Investigation, 117(1), 175–184. Scholar
  63. Macotela, Y., Boucher, J., Tran, T. T., & Kahn, C. R. (2009). Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism. Diabetes, 58(4), 803–812. Scholar
  64. Majka, S. M., Fox, K. E., Psilas, J. C., Helm, K. M., Childs, C. R., Acosta, A. S., Janssen, R. C., Friedman, J. E., Woessner, B. T., Shade, T. R., Varella-Garcia, M., & Klemm, D. J. (2010). De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific. Proceedings of the National Academy of Sciences of the United States of America, 107(33), 14781–14786. Scholar
  65. Mammi, C., Calanchini, M., Antelmi, A., Cinti, F., Rosano, G. M., Lenzi, A., Caprio, M., & Fabbri, A. (2012). Androgens and adipose tissue in males: A complex and reciprocal interplay. International Journal of Endocrinology, 2012, 789653. Scholar
  66. Maquoi, E., Munaut, C., Colige, A., Collen, D., & Lijnen, H. R. (2002). Modulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity. Diabetes, 51(4), 1093–1101.CrossRefPubMedGoogle Scholar
  67. Mariman, E. C., & Wang, P. (2010). Adipocyte extracellular matrix composition, dynamics and role in obesity. Cellular and Molecular Life Sciences, 67(8), 1277–1292.CrossRefPubMedPubMedCentralGoogle Scholar
  68. Masuzaki, H., Ogawa, Y., Isse, N., Satoh, N., Okazaki, T., Shigemoto, M., Mori, K., Tamura, N., Hosoda, K., Yoshimasa, Y., et al. (1995). Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes, 44(7), 855–858.CrossRefPubMedGoogle Scholar
  69. Matsubara, M., Maruoka, S., & Katayose, S. (2002). Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. European Journal of Endocrinology, 147(2), 173–180.CrossRefPubMedGoogle Scholar
  70. Mattacks, C. A., & Pond, C. M. (1999). Interactions of noradrenalin and tumour necrosis factor alpha, interleukin 4 and interleukin 6 in the control of lipolysis from adipocytes around lymph nodes. Cytokine, 11(5), 334–346. Scholar
  71. Melanson, E. L., Sharp, T. A., Schneider, J., Donahoo, W. T., Grunwald, G. K., & Hill, J. O. (2003). Relation between calcium intake and fat oxidation in adult humans. International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 27(2), 196–203. Scholar
  72. Merkestein, M., Cagampang, F. R., & Sellayah, D. (2014). Fetal programming of adipose tissue function: An evolutionary perspective. Mammalian Genome: Official Journal of the International Mammalian Genome Society, 25(9–10), 413–423. Scholar
  73. Mittendorfer, B., Horowitz, J. F., & Klein, S. (2001). Gender differences in lipid and glucose kinetics during short-term fasting. American Journal of Physiology Endocrinology and Metabolism, 281(6), E1333–E1339.CrossRefPubMedGoogle Scholar
  74. Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., Cheetham, C. H., Earley, A. R., Barnett, A. H., Prins, J. B., & O'Rahilly, S. (1997a). Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature, 387(6636), 903–908.CrossRefPubMedGoogle Scholar
  75. Montague, C. T., Prins, J. B., Sanders, L., Digby, J. E., & O’Rahilly, S. (1997b). Depot- and sex-specific differences in human leptin mRNA expression: Implications for the control of regional fat distribution. Diabetes, 46(3), 342–347.CrossRefPubMedGoogle Scholar
  76. Mori, S., Kiuchi, S., Ouchi, A., Hase, T., & Murase, T. (2014). Characteristic expression of extracellular matrix in subcutaneous adipose tissue development and adipogenesis; comparison with visceral adipose tissue. International Journal of Biological Sciences, 10(8), 825–833. Scholar
  77. Munoz-Garach, A., Cornejo-Pareja, I., & Tinahones, F. J. (2016). Does metabolically healthy obesity exist? Nutrients, 8(6). Scholar
  78. Nedergaard, J., Bengtsson, T., & Cannon, B. (2007). Unexpected evidence for active brown adipose tissue in adult humans. American Journal of Physiology Endocrinology and Metabolism, 293(2), E444–E452. Scholar
  79. Nedergaard, J., Bengtsson, T., & Cannon, B. (2010). Three years with adult human brown adipose tissue. Annals of the New York Academy of Sciences, 1212, E20–E36. Scholar
  80. Nguyen, K. D., Qiu, Y., Cui, X., Goh, Y. P., Mwangi, J., David, T., Mukundan, L., Brombacher, F., Locksley, R. M., & Chawla, A. (2011). Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature, 480(7375), 104–108. Scholar
  81. Nielsen, S., Guo, Z., Albu, J. B., Klein, S., O'Brien, P. C., & Jensen, M. D. (2003). Energy expenditure, sex, and endogenous fuel availability in humans. The Journal of Clinical Investigation, 111(7), 981–988. Scholar
  82. Palmer, A. K., & Kirkland, J. L. (2016). Aging and adipose tissue: Potential interventions for diabetes and regenerative medicine. Experimental Gerontology.
  83. Palmer, B. F., & Clegg, D. J. (2015). The sexual dimorphism of obesity. Molecular and Cellular Endocrinology, 402, 113–119. Scholar
  84. Pasarica, M., Gowronska-Kozak, B., Burk, D., Remedios, I., Hymel, D., Gimble, J., Ravussin, E., Bray, G. A., & Smith, S. R. (2009). Adipose tissue collagen VI in obesity. The Journal of Clinical Endocrinology and Metabolism, 94(12), 5155–5162. Scholar
  85. Peirce, V., Carobbio, S., & Vidal-Puig, A. (2014). The different shades of fat. Nature, 510(7503), 76–83. Scholar
  86. Pond, C. M., & Mattacks, C. A. (1998). In vivo evidence for the involvement of the adipose tissue surrounding lymph nodes in immune responses. Immunology Letters, 63(3), 159–167.CrossRefPubMedGoogle Scholar
  87. Pond, C. M., & Mattacks, C. A. (2002). The activation of the adipose tissue associated with lymph nodes during the early stages of an immune response. Cytokine, 17(3), 131–139. Scholar
  88. Pujol, E., Rodriguez-Cuenca, S., Frontera, M., Justo, R., Llado, I., Kraemer, F. B., Gianotti, M., & Roca, P. (2003). Gender- and site-related effects on lipolytic capacity of rat white adipose tissue. Cellular and Molecular Life Sciences: CMLS, 60(9), 1982–1989. Scholar
  89. Ramis, J. M., Salinas, R., Garcia-Sanz, J. M., Moreiro, J., Proenza, A. M., & Llado, I. (2006). Depot- and gender-related differences in the lipolytic pathway of adipose tissue from severely obese patients. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 17(3–4), 173–180. Scholar
  90. Rosen, E. D., & Spiegelman, B. M. (2014). What we talk about when we talk about fat. Cell, 156(1–2), 20–44. Scholar
  91. Sackmann-Sala, L., Berryman, D. E., Munn, R. D., Lubbers, E. R., & Kopchick, J. J. (2012). Heterogeneity among white adipose tissue depots in male C57BL/6J mice. Obesity (Silver Spring), 20(1), 101–111. Scholar
  92. Saito, M., Okamatsu-Ogura, Y., Matsushita, M., Watanabe, K., Yoneshiro, T., Nio-Kobayashi, J., Iwanaga, T., Miyagawa, M., Kameya, T., Nakada, K., Kawai, Y., & Tsujisaki, M. (2009). High incidence of metabolically active brown adipose tissue in healthy adult humans: Effects of cold exposure and adiposity. Diabetes, 58(7), 1526–1531.CrossRefPubMedPubMedCentralGoogle Scholar
  93. Salans, L. B., & Dougherty, J. W. (1971). The effect of insulin upon glucose metabolism by adipose cells of different size. Influence of cell lipid and protein content, age, and nutritional state. The Journal of Clinical Investigation, 50(7), 1399–1410. Scholar
  94. Sanchez-Gurmaches, J., & Guertin, D. A. (2014). Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nature Communications, 5, 4099. Scholar
  95. Sanchez-Gurmaches, J., Hsiao, W. Y., & Guertin, D. A. (2015). Highly selective in vivo labeling of subcutaneous white adipocyte precursors with Prx1-Cre. Stem Cell Reports, 4(4), 541–550. Scholar
  96. Seale, P., Conroe, H. M., Estall, J., Kajimura, S., Frontini, A., Ishibashi, J., Cohen, P., Cinti, S., & Spiegelman, B. M. (2011). Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. The Journal of Clinical Investigation, 121(1), 96–105. Scholar
  97. Seydoux, J., Muzzin, P., Moinat, M., Pralong, W., Girardier, L., & Giacobino, J. P. (1996). Adrenoceptor heterogeneity in human white adipocytes differentiated in culture as assessed by cytosolic free calcium measurements. Cellular Signalling, 8(2), 117–122.CrossRefPubMedGoogle Scholar
  98. Shao, M., Hepler, C., Vishvanath, L., MacPherson, K. A., Busbuso, N. C., & Gupta, R. K. (2017). Fetal development of subcutaneous white adipose tissue is dependent on Zfp423. Molecular Metabolism, 6(1), 111–124. Scholar
  99. Shen, M., Kumar, S. P., & Shi, H. (2014). Estradiol regulates insulin signaling and inflammation in adipose tissue. Hormone Molecular Biology and Clinical Investigation, 17(2), 99–107. Scholar
  100. Shinoda, K., Luijten, I. H., Hasegawa, Y., Hong, H., Sonne, S. B., Kim, M., Xue, R., Chondronikola, M., Cypess, A. M., Tseng, Y. H., Nedergaard, J., Sidossis, L. S., & Kajimura, S. (2015). Genetic and functional characterization of clonally derived adult human brown adipocytes. Nature Medicine, 21(4), 389–394. Scholar
  101. Soukas, A., Cohen, P., Socci, N. D., & Friedman, J. M. (2000). Leptin-specific patterns of gene expression in white adipose tissue. Genes & Development, 14(8), 963–980.Google Scholar
  102. Spencer, M., Unal, R., Zhu, B., Rasouli, N., McGehee, R. E., Jr., Peterson, C. A., & Kern, P. A. (2011). Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance. The Journal of Clinical Endocrinology and Metabolism, 96(12), E1990–E1998. Scholar
  103. Stout, M. B., Justice, J. N., Nicklas, B. J., & Kirkland, J. L. (2017). Physiological aging: Links among adipose tissue dysfunction, diabetes, and frailty. Physiology (Bethesda), 32(1), 9–19. Scholar
  104. Strissel, K. J., Stancheva, Z., Miyoshi, H., Perfield, J. W., 2nd, DeFuria, J., Jick, Z., Greenberg, A. S., & Obin, M. S. (2007). Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes, 56(12), 2910–2918. Scholar
  105. Stubbins, R. E., Holcomb, V. B., Hong, J., & Nunez, N. P. (2012). Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance. European Journal of Nutrition, 51(7), 861–870. Scholar
  106. Sun, K., Kusminski, C. M., & Scherer, P. E. (2011). Adipose tissue remodeling and obesity. The Journal of Clinical Investigation, 121(6), 2094–2101. Scholar
  107. Sun, K., Park, J., Gupta, O. T., Holland, W. L., Auerbach, P., Zhang, N., Goncalves Marangoni, R., Nicoloro, S. M., Czech, M. P., Varga, J., Ploug, T., An, Z., & Scherer, P. E. (2014). Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction. Nature Communications, 5, 3485. Scholar
  108. Tchernof, A., Belanger, C., Morisset, A. S., Richard, C., Mailloux, J., Laberge, P., & Dupont, P. (2006). Regional differences in adipose tissue metabolism in women: Minor effect of obesity and body fat distribution. Diabetes, 55(5), 1353–1360.CrossRefPubMedGoogle Scholar
  109. Tchkonia, T., Lenburg, M., Thomou, T., Giorgadze, N., Frampton, G., Pirtskhalava, T., Cartwright, A., Cartwright, M., Flanagan, J., Karagiannides, I., Gerry, N., Forse, R. A., Tchoukalova, Y., Jensen, M. D., Pothoulakis, C., & Kirkland, J. L. (2007). Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns. American Journal of Physiology. Endocrinology and Metabolism, 292(1), E298–E307.CrossRefPubMedGoogle Scholar
  110. Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010). Fat tissue, aging, and cellular senescence. Aging Cell, 9(5), 667–684. Scholar
  111. Tchoukalova, Y. D., Votruba, S. B., Tchkonia, T., Giorgadze, N., Kirkland, J. L., & Jensen, M. D. (2010). Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proceedings of the National Academy of Sciences of the United States of America, 107(42), 18226–18231. Scholar
  112. Thomou, T., Mori, M. A., Dreyfuss, J. M., Konishi, M., Sakaguchi, M., Wolfrum, C., Rao, T. N., Winnay, J. N., Garcia-Martin, R., Grinspoon, S. K., Gorden, P., & Kahn, C. R. (2017). Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature.
  113. Townsend, K. L., & Tseng, Y. H. (2015). Of mice and men: Novel insights regarding constitutive and recruitable brown adipocytes. International Journal of Obesity Supplements, 5(Suppl 1), S15–S20. Scholar
  114. Tran, T. T., & Kahn, C. R. (2010). Transplantation of adipose tissue and stem cells: Role in metabolism and disease. Nature Reviews Endocrinology, 6(4), 195–213. Scholar
  115. Troike, K. M., Henry, B. E., Jensen, E. A., Young, J. A., List, E. O., Kopchick, J. J., & Berryman, D. E. (2017). Impact of growth hormone on regulation of adipose tissue. Comprehensive Physiology. Jun 18;7(3):819–840.
  116. Varlamov, O., Chu, M., Cornea, A., Sampath, H., & Roberts, C. T., Jr. (2015). Cell-autonomous heterogeneity of nutrient uptake in white adipose tissue of rhesus macaques. Endocrinology, 156(1), 80–89. Scholar
  117. Vatier, C., Fetita, S., Boudou, P., Tchankou, C., Deville, L., Riveline, J. P., Young, J., Mathivon, L., Travert, F., Morin, D., Cahen, J., Lascols, O., Andreelli, F., Reznik, Y., Mongeois, E., Madelaine, I., Vantyghem, M. C., Gautier, J. F., & Vigouroux, C. (2016). One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes. Diabetes, Obesity and Metabolism, 18(7), 693–697. Scholar
  118. Vijgen, G. H., Bouvy, N. D., Teule, G. J., Brans, B., Schrauwen, P., & van Marken Lichtenbelt, W. D. (2011). Brown adipose tissue in morbidly obese subjects. PLoS One, 6(2), e17247. Scholar
  119. Villarroya, J., Cereijo, R., & Villarroya, F. (2013). An endocrine role for brown adipose tissue? American Journal of Physiology Endocrinology and Metabolism, 305(5), E567–E572. Scholar
  120. Vitali, A., Murano, I., Zingaretti, M. C., Frontini, A., Ricquier, D., & Cinti, S. (2012). The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. Journal of Lipid Research, 53(4), 619–629. Scholar
  121. Wang, G. X., Zhao, X. Y., Meng, Z. X., Kern, M., Dietrich, A., Chen, Z., Cozacov, Z., Zhou, D., Okunade, A. L., Su, X., Li, S., Bluher, M., & Lin, J. D. (2014). The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nature Medicine, 20(12), 1436–1443. Scholar
  122. Wang, H., Liu, L., Lin, J. Z., Aprahamian, T. R., & Farmer, S. R. (2016). Browning of white adipose tissue with roscovitine induces a distinct population of UCP1+ adipocytes. Cell Metabolism, 24(6), 835–847. Scholar
  123. Wang, Q. A., Tao, C., Gupta, R. K., & Scherer, P. E. (2013). Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nature Medicine, 19(10), 1338–1344. Scholar
  124. Wang, S. P., Laurin, N., Himms-Hagen, J., Rudnicki, M. A., Levy, E., Robert, M. F., Pan, L., Oligny, L., & Mitchell, G. A. (2001). The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obesity Research, 9(2), 119–128.CrossRefPubMedGoogle Scholar
  125. Wang, W., & Seale, P. (2016). Control of brown and beige fat development. Nature Reviews. Molecular Cell Biology, 17(11), 691–702. Scholar
  126. Wikstrom, J. D., Mahdaviani, K., Liesa, M., Sereda, S. B., Si, Y., Las, G., Twig, G., Petrovic, N., Zingaretti, C., Graham, A., Cinti, S., Corkey, B. E., Cannon, B., Nedergaard, J., & Shirihai, O. S. (2014). Hormone-induced mitochondrial fission is utilized by brown adipocytes as an amplification pathway for energy expenditure. The EMBO Journal, 33(5), 418–436. Scholar
  127. Wong, R. H., & Sul, H. S. (2010). Insulin signaling in fatty acid and fat synthesis: A transcriptional perspective. Current Opinion in Pharmacology, 10(6), 684–691. Scholar
  128. Wu, J., Bostrom, P., Sparks, L. M., Ye, L., Choi, J. H., Giang, A. H., Khandekar, M., Virtanen, K. A., Nuutila, P., Schaart, G., Huang, K., Tu, H., van Marken Lichtenbelt, W. D., Hoeks, J., Enerback, S., Schrauwen, P., & Spiegelman, B. M. (2012). Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell, 150(2), 366–376. Scholar
  129. Wueest, S., Schoenle, E. J., & Konrad, D. (2012a). Depot-specific differences in adipocyte insulin sensitivity in mice are diet- and function-dependent. Adipocytes, 1(3), 153–156. Scholar
  130. Wueest, S., Yang, X., Liu, J., Schoenle, E. J., & Konrad, D. (2012b). Inverse regulation of basal lipolysis in perigonadal and mesenteric fat depots in mice. American Journal of Physiology Endocrinology and Metabolism, 302(1), E153–E160. Scholar
  131. Xue, R., Lynes, M. D., Dreyfuss, J. M., Shamsi, F., Schulz, T. J., Zhang, H., Huang, T. L., Townsend, K. L., Li, Y., Takahashi, H., Weiner, L. S., White, A. P., Lynes, M. S., Rubin, L. L., Goodyear, L. J., Cypess, A. M., & Tseng, Y. H. (2015). Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes. Nature Medicine, 21(7), 760–768. Scholar
  132. Yaghootkar, H., Scott, R. A., White, C. C., Zhang, W., Speliotes, E., Munroe, P. B., Ehret, G. B., Bis, J. C., Fox, C. S., Walker, M., Borecki, I. B., Knowles, J. W., Yerges-Armstrong, L., Ohlsson, C., Perry, J. R., Chambers, J. C., Kooner, J. S., Franceschini, N., Langenberg, C., Hivert, M. F., Dastani, Z., Richards, J. B., Semple, R. K., & Frayling, T. M. (2014). Genetic evidence for a normal-weight “metabolically obese” phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes, 63(12), 4369–4377. Scholar
  133. Yin, D., Clarke, S. D., Peters, J. L., & Etherton, T. D. (1998). Somatotropin-dependent decrease in fatty acid synthase mRNA abundance in 3T3-F442A adipocytes is the result of a decrease in both gene transcription and mRNA stability. The Biochemical Journal, 331(Pt. 3), 815–820.CrossRefPubMedPubMedCentralGoogle Scholar
  134. Zhu, Y., Gao, Y., Tao, C., Shao, M., Zhao, S., Huang, W., Yao, T., Johnson, J. A., Liu, T., Cypess, A. M., Gupta, O., Holland, W. L., Gupta, R. K., Spray, D. C., Tanowitz, H. B., Cao, L., Lynes, M. D., Tseng, Y. H., Elmquist, J. K., Williams, K. W., Lin, H. V., & Scherer, P. E. (2016). Connexin 43 mediates white adipose tissue beiging by facilitating the propagation of sympathetic neuronal signals. Cell Metabolism, 24(3), 420–433. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Katie M. Troike
    • 1
  • Kevin Y. Lee
    • 2
  • Edward O. List
    • 3
  • Darlene E. Berryman
    • 4
    Email author
  1. 1.The Diabetes Institute, Konneker Research LabsOhio UniversityAthensUSA
  2. 2.Department of Biomedical Sciences, The Diabetes InstituteHeritage College of Osteopathic MedicineAthensUSA
  3. 3.Edison Biotechnology Institute, Konneker Research LabsOhio UniversityAthensUSA
  4. 4.The Diabetes Institute, Department of Biomedical Sciences, Heritage College of Osteopathic MedicineOhio UniversityAthensUSA

Personalised recommendations