Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Adipocytes as regulators of energy balance and glucose homeostasis

Abstract

Adipocytes have been studied with increasing intensity as a result of the emergence of obesity as a serious public health problem and the realization that adipose tissue serves as an integrator of various physiological pathways. In particular, their role in calorie storage makes adipocytes well suited to the regulation of energy balance. Adipose tissue also serves as a crucial integrator of glucose homeostasis. Knowledge of adipocyte biology is therefore crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. Furthermore, the rational manipulation of adipose physiology is a promising avenue for therapy of these conditions.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Energy homeostasis depends upon the balance between caloric intake and energy expenditure.
Figure 2: Adipocytes regulate energy balance by endocrine and non-endocrine mechanisms.
Figure 3: Glucose homeostasis requires the coordinated actions of various organs.
Figure 4: Adipocytes secrete proteins with varied effects on glucose homeostasis.
Figure 5: Adipocyte-derived non-esterified fatty acids have several effects on glucose homeostasis.

Similar content being viewed by others

References

  1. Mokdad, A. H. et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. J. Am. Med. Assoc. 289, 76–79 (2003).

    Article  Google Scholar 

  2. Bray, G. A. & Bellanger, T. Epidemiology, trends, and morbidities of obesity and the metabolic syndrome. Endocrine 29, 109–117 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Trayhurn, P. Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol. Scand. 184, 285–293 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Pond, C. M. The Fats of Life (Cambridge Univ. Press, Cambridge, 1998).

    Book  Google Scholar 

  5. Giorgino, F., Laviola, L. & Eriksson, J. W. Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies. Acta Physiol. Scand. 183, 13–30 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Green, H. & Kehinde, O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 5, 19–27 (1975).

    Article  CAS  PubMed  Google Scholar 

  7. Farmer, S.R. Transcriptional control of adipocyte formation. Cell Metab. 4, 263–273 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hansen, J. B. & Kristiansen, K. Regulatory circuits controlling white versus brown adipocyte differentiation. Biochem. J. 398, 153–168 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rosen, E. D. et al. C/EBPα induces adipogenesis through PPARγ: a unified pathway. Genes Dev. 16, 22–26 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rosen, E. D. et al. PPARγ is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4, 611–617 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Tontonoz, P., Hu, E. & Spiegelman, B. M. Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell 79, 1147–1156 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Oishi, Y. et al. Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab. 1, 27–39 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Mori, T. et al. Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J. Biol. Chem. 280, 12867–12875 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Banerjee, S. S. et al. The Kruppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-γ expression and adipogenesis. J. Biol. Chem. 278, 2581–2584 (2003).

    Article  PubMed  CAS  Google Scholar 

  15. Chen, Z., Torrens, J. I., Anand, A., Spiegelman, B. M. & Friedman, J. M. Krox20 stimulates adipogenesis via C/EBPβ-dependent and -independent mechanisms. Cell Metab. 1, 93–106 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Akerblad, P., Lind, U., Liberg, D., Bamberg, K. & Sigvardsson, M. Early B-cell factor (O/E-1) is a promoter of adipogenesis and involved in control of genes important for terminal adipocyte differentiation. Mol. Cell Biol. 22, 8015–8025 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hansen, J. B. et al. Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation. Proc. Natl Acad. Sci. USA 101, 4112–4117 (2004).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Scime, A. et al. Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1α. Cell Metab. 2, 283–295 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Picard, F. et al. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell 111, 931–941 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Puigserver, P. et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92, 829–839 (1998).

    Article  CAS  PubMed  Google Scholar 

  21. Puigserver, P. Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-α. Int. J. Obes. (Lond.) 29 (Suppl. 1), S5–S9 (2005).

    Article  CAS  Google Scholar 

  22. Uldry, M. et al. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab. 3, 333–341 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Schwartz, M. W. et al. Is the energy homeostasis system inherently biased toward weight gain? Diabetes 52, 232–238 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Abizaid, A., Gao, Q. & Horvath, T. L. Thoughts for food: brain mechanisms and peripheral energy balance. Neuron 51, 691–702 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Mauer, M. M., Harris, R. B. & Bartness, T. J. The regulation of total body fat: lessons learned from lipectomy studies. Neurosci. Biobehav. Rev. 25, 15–28 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Friedman, J. M. Leptin and the regulation of body weight. Harvey Lect. 95, 107–136 (1999).

    CAS  PubMed  Google Scholar 

  27. Friedman, J. M. The function of leptin in nutrition, weight, and physiology. Nutr. Rev. 60, S1–S14 (2002).

    Article  PubMed  Google Scholar 

  28. Halaas, J. L. et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543–546 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Pelleymounter, M. A. et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–543 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P. & Baskin, D. G. Identification of targets of leptin action in rat hypothalamus. J. Clin. Invest. 98, 1101–1106 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bjorbaek, C. & Kahn, B. B. Leptin signaling in the central nervous system and the periphery. Recent Prog. Horm. Res. 59, 305–331 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Fei, H. et al. Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc. Natl Acad. Sci. USA 94, 7001–7005 (1997).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  33. Balthasar, N. et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493–505 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Grill, H. J. Distributed neural control of energy balance: contributions from hindbrain and hypothalamus. Obesity (Silver Spring) 14 (Suppl. 5), 216S–221S (2006).

    Google Scholar 

  35. Bartness, T. J. & Bamshad, M. Innervation of mammalian white adipose tissue: implications for the regulation of total body fat. Am. J. Physiol. 275, R1399–R1411 (1998).

    CAS  PubMed  Google Scholar 

  36. Bartness, T. J., Kay Song, C., Shi, H., Bowers, R. R. & Foster, M. T. Brain–adipose tissue cross talk. Proc. Nutr. Soc. 64, 53–64 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Yamada, T. et al. Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: neuronal involvement in food-intake regulation. Cell Metab. 3, 223–229 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Bachman, E. S. et al. βAR signaling required for diet-induced thermogenesis and obesity resistance. Science 297, 843–845 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  39. Lowell, B. B. et al. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366, 740–742 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  40. Enerback, S. et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387, 90–94 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A. & Wakil, S. J. Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291, 2613–2616 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  42. Parker, M. G., Christian, M. & White, R. The nuclear receptor co-repressor RIP140 controls the expression of metabolic gene networks. Biochem. Soc. Trans. 34, 1103–1106 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Qi, L. et al. TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science 312, 1763–1766 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  44. Herman, M. A. & Kahn, B. B. Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony. J. Clin. Invest. 116, 1767–1775 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tirone, T. A. & Brunicardi, F. C. Overview of glucose regulation. World J. Surg. 25, 461–467 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Kahn, B. B. Lilly lecture 1995. Glucose transport: pivotal step in insulin action. Diabetes 45, 1644–1654 (1996).

    Article  CAS  PubMed  Google Scholar 

  47. Schwartz, M. W. et al. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes 45, 531–535 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Farooqi, I. S. et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 110, 1093–1103 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S. & Goldstein, J. L. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401, 73–76 (1999).

    Article  ADS  CAS  PubMed  Google Scholar 

  50. Oral, E. A. et al. Leptin-replacement therapy for lipodystrophy. N. Engl. J. Med. 346, 570–578 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Heymsfield, S. B. et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. J. Am Med. Assoc. 282, 1568–1575 (1999).

    Article  CAS  Google Scholar 

  52. Minokoshi, Y. et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415, 339–343 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  53. Kamohara, S., Burcelin, R., Halaas, J. L., Friedman, J. M. & Charron, M. J. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389, 374–377 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  54. Kieffer, T. J. & Habener, J. F. The adipoinsular axis: effects of leptin on pancreatic β-cells. Am. J. Physiol. Endocrinol. Metab. 278, E1–E14 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Covey, S. D. et al. The pancreatic β cell is a key site for mediating the effects of leptin on glucose homeostasis. Cell Metab. 4, 291–302 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Kadowaki, T. et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest. 116, 1784–1792 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Waki, H. et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J. Biol. Chem. 278, 40352–40363 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Pajvani, U. B. et al. Structure–function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications for metabolic regulation and bioactivity. J. Biol. Chem. 278, 9073–9085 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Yamauchi, T. et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423, 762–769 (2003).

    Article  ADS  CAS  PubMed  Google Scholar 

  60. Hug, C. et al. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc. Natl Acad. Sci. USA 101, 10308–10313 (2004).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  61. Arita, Y. et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. 257, 79–83 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Yatagai, T. et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus. Metabolism 52, 1274–1278 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Hotta, K. et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 50, 1126–1133 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Kubota, N. et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J. Biol. Chem. 277, 25863–25866 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Ma, K. et al. Increased β-oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J. Biol. Chem. 277, 34658–34661 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Maeda, N. et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature Med. 8, 731–737 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  67. Nawrocki, A. R. et al. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor γ agonists. J. Biol. Chem. 281, 2654–2660 (2006).

    Article  CAS  PubMed  Google Scholar 

  68. Kubota, N. et al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J. Biol. Chem. 281, 8748–8755 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Maeda, N. et al. PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50, 2094–2099 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Winzell, M. S., Nogueiras, R., Dieguez, C. & Ahren, B. Dual action of adiponectin on insulin secretion in insulin-resistant mice. Biochem. Biophys. Res. Commun. 321, 154–160 (2004).

    Article  PubMed  CAS  Google Scholar 

  71. Fukuhara, A. et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307, 426–430 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  72. Stephens, J. M. & Vidal-Puig, A. J. An update on visfatin/pre-B cell colony-enhancing factor, an ubiquitously expressed, illusive cytokine that is regulated in obesity. Curr. Opin. Lipidol. 17, 128–131 (2006).

    Article  CAS  PubMed  Google Scholar 

  73. Yang, H., Lavu, S. & Sinclair, D. A. Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity? Exp. Gerontol. 41, 718–726 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Yang, R. Z. et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am. J. Physiol. Endocrinol. Metab. 290, E1253–E1261 (2006).

    Article  CAS  PubMed  Google Scholar 

  75. Hotamisligil, G. S. The role of TNFα and TNF receptors in obesity and insulin resistance. J. Intern. Med. 245, 621–625 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821–1830 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Carey, A. L. et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55, 2688–2697 (2006).

    Article  CAS  PubMed  Google Scholar 

  78. Rotter, V., Nagaev, I. & Smith, U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-α, overexpressed in human fat cells from insulin-resistant subjects. J. Biol. Chem. 278, 45777–45784 (2003).

    Article  CAS  PubMed  Google Scholar 

  79. Hirosumi, J. et al. A central role for JNK in obesity and insulin resistance. Nature 420, 333–336 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  80. Shoelson, S. E., Lee, J. & Yuan, M. Inflammation and the IKKβ/IκB/NF-κB axis in obesity- and diet-induced insulin resistance. Int. J. Obes. Relat. Metab. Disord. 27 (Suppl. 3), S49–S52 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Howard, J. K. & Flier, J. S. Attenuation of leptin and insulin signaling by SOCS proteins. Trends Endocrinol. Metab. 17, 365–371 (2006).

    Article  CAS  PubMed  Google Scholar 

  82. Houstis, N., Rosen, E. D. & Lander, E. S. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440, 944–948 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  83. Steppan, C. M. et al. A family of tissue-specific resistin-like molecules. Proc. Natl Acad. Sci. USA 98, 502–506 (2001).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  84. Steppan, C. M. et al. The hormone resistin links obesity to diabetes. Nature 409, 307–312 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  85. Banerjee, R. R. et al. Regulation of fasted blood glucose by resistin. Science 303, 1195–1198 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  86. Steppan, C. M. & Lazar, M. A. The current biology of resistin. J. Intern. Med. 255, 439–447 (2004).

    Article  CAS  PubMed  Google Scholar 

  87. Patel, S. D., Rajala, M. W., Rossetti, L., Scherer, P. E. & Shapiro, L. Disulfide-dependent multimeric assembly of resistin family hormones. Science 304, 1154–1158 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  88. Kaser, S. et al. Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem. Biophys. Res. Commun. 309, 286–290 (2003).

    Article  CAS  PubMed  Google Scholar 

  89. Patel, L. et al. Resistin is expressed in human macrophages and directly regulated by PPARγ activators. Biochem. Biophys. Res. Commun. 300, 472–476 (2003).

    Article  CAS  PubMed  Google Scholar 

  90. Yang, Q. et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436, 356–362 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  91. Graham, T. E. et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N. Engl. J. Med. 354, 2552–2563 (2006).

    Article  CAS  PubMed  Google Scholar 

  92. Roden, M. et al. Mechanism of free fatty acid-induced insulin resistance in humans. J. Clin. Invest. 97, 2859–2865 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Roden, M. et al. Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans. Diabetes 49, 701–707 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Griffin, M. E. et al. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes 48, 1270–1274 (1999).

    Article  CAS  PubMed  Google Scholar 

  95. Schmitz-Peiffer, C. et al. Alterations in the expression and cellular localization of protein kinase C isozymes epsilon and theta are associated with insulin resistance in skeletal muscle of the high-fat-fed rat. Diabetes 46, 169–178 (1997).

    Article  CAS  PubMed  Google Scholar 

  96. Paolisso, G. et al. Does free fatty acid infusion impair insulin action also through an increase in oxidative stress? J. Clin. Endocrinol. Metab. 81, 4244–4248 (1996).

    Article  CAS  PubMed  Google Scholar 

  97. Hajduch, E. et al. Ceramide impairs the insulin-dependent membrane recruitment of protein kinase B leading to a loss in downstream signalling in L6 skeletal muscle cells. Diabetologia 44, 173–183 (2001).

    Article  CAS  PubMed  Google Scholar 

  98. Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015–3025 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Song, M. J., Kim, K. H., Yoon, J. M. & Kim, J. B. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. Biochem. Biophys. Res. Commun. 346, 739–745 (2006).

    Article  CAS  PubMed  Google Scholar 

  100. Eldor, R. & Raz, I. Lipotoxicity versus adipotoxicity — the deleterious effects of adipose tissue on beta cells in the pathogenesis of type 2 diabetes. Diabetes Res. Clin. Pract. 74, S3–S8 (2006).

    Article  CAS  Google Scholar 

  101. Lowell, B. B. & Shulman, G. I. Mitochondrial dysfunction and type 2 diabetes. Science 307, 384–387 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  102. Simha, V. & Garg, A. Lipodystrophy: lessons in lipid and energy metabolism. Curr. Opin. Lipidol. 17, 162–169 (2006).

    Article  CAS  PubMed  Google Scholar 

  103. Yamauchi, T. et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature Med. 7, 941–946 (2001).

    Article  CAS  PubMed  Google Scholar 

  104. Weisberg, S. P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).

    Article  CAS  PubMed  PubMed Central  MathSciNet  Google Scholar 

  105. Weisberg, S. P. et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J. Clin. Invest. 116, 115–124 (2006).

    Article  CAS  PubMed  Google Scholar 

  106. Kanda, H. et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest. 116, 1494–1505 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kamei, N. et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J. Biol. Chem. 281, 26602–26614 (2006).

    Article  CAS  PubMed  Google Scholar 

  108. Di Gregorio, G. B. et al. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes 54, 2305–2313 (2005).

    Article  CAS  PubMed  Google Scholar 

  109. Gnudi, L., Tozzo, E., Shepherd, P. R., Bliss, J. L. & Kahn, B. B. High level overexpression of glucose transporter-4 driven by an adipose-specific promoter is maintained in transgenic mice on a high fat diet, but does not prevent impaired glucose tolerance. Endocrinology 136, 995–1002 (1995).

    Article  CAS  PubMed  Google Scholar 

  110. Abel, E. D. et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 409, 729–733 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  111. Fukuchi, K. et al. Radionuclide imaging metabolic activity of brown adipose tissue in a patient with pheochromocytoma. Exp. Clin. Endocrinol. Diabetes 112, 601–603 (2004).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank B. Lowell and M. Herman for a critical reading of the manuscript.

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosen, E., Spiegelman, B. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444, 847–853 (2006). https://doi.org/10.1038/nature05483

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05483

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing