에너지 항상성 조절 및 비만의 병태생리에 관한 최신지견

Recent Advances in Regulating Energy Homeostasis and Obesity

  • 박미정 (인제대학교 의과대학 상계백병원 소아과)
  • Park, Mi Jung (Department of Pediatrics, Sanggye Paik Hospital, Inje University College of Medicine)
  • 투고 : 2005.01.24
  • 심사 : 2004.01.25
  • 발행 : 2005.02.15

초록

New insights in the complex metabolic pathways and its control mechanism for energy homeostasis have refined our understanding of the pathophysiology of obesity. It is now recognized that there are several additional regulatory mechanism such as peripheral signals including leptin, ghrelin, GLP-1 and PYY and cellular signals including uncoupling proteins and ${\beta}$ Adrenergic receptors, which contribute to the regulation of food intake and energy expenditure, respectively. In addition, the function of adipocyte as an endocrine organ in energy homeostasis has been recently emphasized. Recent findings suggest that elevated levels of adipokines, such as leptin, adiponectin, resistin and TNF-${\alpha}$, in addition to increased free fatty acid level could be related to the pathophysiology of insulin resistance in obesity. For effective treatments and prevention of obesity, further studies on the circuits of neural and endocrine interactions in the regulation of energy homeostasis are needed.

키워드

과제정보

연구 과제 주관 기관 : 인제연구장학재단

참고문헌

  1. Friedman JM. Modern science versus the stigma of obesity. Nat Med 2004;10:563-9 https://doi.org/10.1038/nm0604-563
  2. Webber J. Energy balance in obesity. Proc Nutr Soc 2003; 62:539-43 https://doi.org/10.1079/PNS2003256
  3. Miller J, Rosenbloom A, Silverstein J. Childhood obesity. J Clin Endocrinol Metab 2004;89:4211-8 https://doi.org/10.1210/jc.2004-0284
  4. Flier JS. Obesity wars : molecular progress confronts an expanding epidemic. Cell 2004;23;116:337-50
  5. Yanovski SZ, Yanovski JA. Obesity. N Engl J Med 2002; 346:591-602 https://doi.org/10.1056/NEJMra012586
  6. Hofbauer KG. Molecular pathways to obesity. Int J Obes Relat Metab Disord 2002;26(2 Suppl):18S-27S
  7. Lowell BB, Spiegelman BM. Towards a molecular understanding of adaptive thermogenesis. Nature 2000;404:652-60 https://doi.org/10.1038/35007527
  8. Lowell BB, Bachman ES. Beta-Adrenergic receptors, dietinduced thermogenesis, and obesity. J Biol Chem 2003;278: 29385-8 https://doi.org/10.1074/jbc.R300011200
  9. Gale SM, Castracane VD, Mantzoros CS. Energy homeostasis, obesity and eating disorders : recent advances in endocrinology. J Nutr 2004;134:295-8 https://doi.org/10.1093/jn/134.2.295
  10. Korner J, Leibel RL. To eat or not to eat - how the gut talks to the brain. N Engl J Med 2004;349:926-8 https://doi.org/10.1056/NEJMp038114
  11. Havel PJ. Peripheral signals conveying metabolic information to the brain : short-term and long-term regulation of food intake and energy homeostasis. Exp Biol Med 2001; 226:963-77 https://doi.org/10.1177/153537020122601102
  12. Neary NM, Goldstone AP, Bloom SR. Appetite regulation: from the gut to the hypothalamus. Clin Endocrinol 2004; 60:153-60 https://doi.org/10.1046/j.1365-2265.2003.01839.x
  13. Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2001;40404:661-71
  14. Lubrano-Berthelier C, Cavazos M, Dubern B, Shapiro A, Stunff CL, Zhang S, et al. Molecular genetics of human obesity-associated MC4R mutations. Ann N Y Acad Sci 2003;994:49-57 https://doi.org/10.1111/j.1749-6632.2003.tb03161.x
  15. Park MJ. Neuroendocrine control of food intake. J Korean Pediatr Endocrinol 2002;7:51-60
  16. Jequier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 2002;967:379-88
  17. Meier U, Gressner AM. Endocrine regulation of energy metabolism : review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 2004;50:1511-25 https://doi.org/10.1373/clinchem.2004.032482
  18. Korner J, Aronne LJ. Pharmacological approaches to weight reduction : therapeutic targets. J Clin Endocrinol Metab 2004;89:2616-21 https://doi.org/10.1210/jc.2004-0341
  19. Jandacek RJ, Woods SC. Pharmaceutical approaches to the treatment of obesity. Drug Discov Today 2004;9:874-80 https://doi.org/10.1016/S1359-6446(04)03244-1
  20. Halford JC. Clinical pharmacotherapy for obesity : current drugs and those in advanced development. Curr Drug Targets 2004;5:637-46 https://doi.org/10.2174/1389450043345191
  21. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest 2000;106:473-81 https://doi.org/10.1172/JCI10842
  22. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548-56 https://doi.org/10.1210/jc.2004-0395
  23. Havel PJ. Update on adipocyte hormones : regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 2004;53(1 Suppl):143S-151S https://doi.org/10.2337/diabetes.53.2007.S143
  24. Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell 2001;104:531-43 https://doi.org/10.1016/S0092-8674(01)00240-9
  25. Kersten S. Peroxisome proliferator activated receptors and obesity. European Journal of Pharmacology 2002;440:223-4 https://doi.org/10.1016/S0014-2999(02)01431-0
  26. Kim JB, Park JY. Molecular insights into fat cell differentiation and functional roles of adipocytokines. J Korean Society of Endocrinol 2002;17:1-7
  27. Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med 2004;10:355-61 https://doi.org/10.1038/nm1025
  28. Haluzik M, Parizkova J, Haluzik MM. Adiponectin and its role in the obesity-induced insulin resistance and related complications. Physiol Res 2004;53:123-9
  29. Goldfine AB, Kahn CR. Adiponectin : linking the fat cell to insulin sensitivity. Lancet 2003;362:1431-2 https://doi.org/10.1016/S0140-6736(03)14727-7
  30. Shuldiner AR, Yang R, Gong DW. Resistin, obesity and insulin resistance-the emerging role of the adipocyte as an endocrine organ. N Engl J Med 2001;345:1345-6 https://doi.org/10.1056/NEJM200111013451814
  31. Wolf G. Insulin resistance and obesity : resistin, a hormone secreted by adipose tissue. Nutr Rev 2004;62:389-94 https://doi.org/10.1111/j.1753-4887.2004.tb00009.x
  32. Kadowaki T, Hara K, Yamauchi T, Terauchi Y, Tobe K, Nagai R. Molecular mechanism of insulin resistance and obesity. Exp Biol Med 2003;228:1111-7 https://doi.org/10.1177/153537020322801003
  33. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001;414:799-806 https://doi.org/10.1038/414799a
  34. Flier JS. Diabetes. The missing link with obesity? Nature 2001;409:292-3 https://doi.org/10.1038/35053251
  35. Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 2004;89:2595-600 https://doi.org/10.1210/jc.2004-0372
  36. Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA. The adipocyte : a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab 2001;280:E827-47 https://doi.org/10.1152/ajpendo.2001.280.6.E827
  37. Marette A. Molecular mechanisms of inflammation in obesity- linked insulin resistance. Int J Obes Relat Metab Disord 2003;27(3 Suppl):46S-48S https://doi.org/10.1038/sj.ijo.0802500
  38. Dandona P, Aljada A, Bandyopadhyay A. Inflammation : the link between insulin resistance, obesity and diabetes. Trends Immunol 2004;25:4-7 https://doi.org/10.1016/j.it.2003.10.013