Эффекты бариатрических операций на уровень гормонов, регулирующих массу тела. В чем основа успеха?

Растущая заболеваемость ожирением и сахарным диабетом 2 типа сделала бариатрическую хирургию широко распространенным методом лечения. Эффективность бариатрических операций в лечении ожирения и сопутствующих метаболических нарушений хорошо освещена в литературе. Тем не менее, результаты этих вмешательств не всегда коррелируют с типом операции. По-прежнему до конца не изучены механизмы влияния бариатрических вмешательств на инсулинорезистенность, энтеро-инсулярную ось, адипокины. Понимание этих механизмов позволит более точно определять показания к хирургическому лечению и повысить эффективность операции у конкретного пациента. Обзор посвящен влиянию различных типов бариатрических операций на уровень гормонов жировой ткани и желудочно-кишечного тракта, участвующих в регуляции аппетита, жирового и углеводного обмена. В статье рассмотрены современные представления о воздействии бариатрических вмешательств на метаболические нарушения при ожирение.

1. Oecd. Health at a Glance: Europe. OECD Publishing; 2013.

2. TOS/AHA/ACC Guideline for the Management of Overweight and Obesity in Adults: A Practice Guidelines and The Obesity Society Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. 2013.

3. Standards of medical care in diabetes – 2013. American Diabetes Association. American Diabetes Association. Diabetes Care 2013;36(1):11–66.

4. Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, et al. Weight and Type 2 Diabetes after Bariatric Surgery: Systematic Review and Meta-analysis. The American Journal of Medicine 2009;122(3):248–256. doi: 10.1016/j.amjmed.2008.09.041.

5. Kim J, van de Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J. Clin. Invest 2007;117(9):2621–2637. Available from: PMID: 17717599. doi: 10.1172/JCI31021.

6. Lembo G, Vecchione C, Fratta L, Marino G, Trimarco V, d'Amati G, et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 2000;49(2):293–297. doi: 10.2337/diabetes.49.2.293.

7. Bouloumie A, Marumo T, Lafontan M, Busse R. Leptin induces oxidative stress in human endothelial cells. FASEB J 1999;13(10):1231–8.

8. Quehenberger P, Exner M, Sunder-Plassmann R, Ruzicka K, Bieglmayer C, Endler G, et al. Leptin Induces Endothelin-1 in Endothelial Cells In Vitro. Circulation Research 2002;90(6):711–718. PMID: 11934840. doi: 10.1161/01.RES.0000014226.74709.90.

9. Bouloumie A, Drexler HCA, Lafontan M, Busse R. Leptin, the Product of Ob Gene, Promotes Angiogenesis. Circulation Research 1998;83(10):1059–1066. PMID: 9815153. doi: 10.1161/01.RES.83.10.1059.

10. Parhami F, Tintut Y, Ballard A, Fogelman AM, Demer LL. Leptin Enhances the Calcification of Vascular Cells : Artery Wall as a Target of Leptin. Circulation Research 2001;88(9):954–960. doi: 10.1161/hh0901.090975.

11. Bodary PF, Westrick RJ, Wickenheiser KJ, Shen Y, Eitzman DT. Effect of Leptin on Arterial Thrombosis Following Vascular Injury in Mice. JAMA 2002;287(13):1706–1709. PMID: 11926895. doi: 10.1001/jama.287.13.1706.

12. Shek E. W, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension 1998;31(1 Pt 2):409–14.

13. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, et al. Kihara S,Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin. Nat Med. 2002 Jul;8(7): 731–7. Epub 2002.

14. K1 O, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A, et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension. 2006 Jun;47(6): 1108–16. Epub 2006;47(6):1108-16.

15. Aprahamian TR, Sam F. Adiponectin in Cardiovascular Inflammation and Obesity. International Journal of Inflammation 2011;2011:1–8. PMID: 21941676. doi: 10.4061/2011/376909.

16. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity. Biochemical and Biophysical Research Communications 1999;257(1):79–83. doi: 10.1006/bbrc.1999.0255.

17. Geloneze B, Tambascia MA, Repetto EM, Pereira SG, Pareja JC, Magna LA. Serum Leptin Levels After Bariatric Surgery Across a Range of Glucose Tolerance from Normal to Diabetes. Obes Surg 2001;11(6):693–698. PMID: 11775566. doi: 10.1381/09608920160558623.

18. Nijhuis J, van Dielen FMH, Buurman WA, Greve JWM. Ghrelin, Leptin and Insulin Levels after Restrictive Surgery: a 2-Year Follow-up Study. Obes Surg 2004;14(6):783–787. PMID: 15318982. doi: 10.1381/0960892041590980.

19. Hu C, Zhang G, Sun D, Han H, Hu S. Duodenal–Jejunal Bypass Improves Glucose Metabolism and Adipokine Expression Independently of Weight Loss in a Diabetic Rat Model. OBES SURG 2013;23(9):1436–1444. doi: 10.1007/s11695-013-0976-1.

20. Woelnerhanssen B, Peterli R, Steinert RE, Peters T, Borbély Y, Beglinger C. Effects of postbariatric surgery weight loss on adipokines and metabolic parameters: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy—a prospective randomized trial. Surgery for Obesity and Related Diseases 2011;7(5):561–568. doi: 10.1016/j.soard.2011.01.044.

21. Mortensen K, Petersen LL, Ørskov C. Colocalization of GLP-1 and GIP in Human and Porcine Intestine. Annals of the New York Academy of Sciences 2006;921(1):469–472. doi: 10.1111/j.1749-6632.2000.tb07017.x.

22. Thrainsdottir I, Malmberg K, Olsson A, Gutniak M, Ryden L. Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure. Diab Vasc Dis Res 2004;1(1):40–43. PMID: 16305055. doi: 10.3132/dvdr.2004.005.

23. Irwin N, Flatt PR. Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia 2009;52(9):1724–1731. PMID: 19533083. doi: 10.1007/s00125-009-1422-8.

24. Asmar M, Simonsen L, Madsbad S, Stallknecht B, Holst JJ, Bulow J. Glucose-Dependent Insulinotropic Polypeptide May Enhance Fatty Acid Re-esterification in Subcutaneous Abdominal Adipose Tissue in Lean Humans. Diabetes 2010;59(9):2160–2163. PMID: 20547981. doi: 10.2337/db10-0098.

25. Acitores A, González N, Sancho V, Arnés L, Valverde I, Malaisse WJ, et al. Participation of protein kinases in the stimulant action of GLP-1 upon 2-deoxy-D-glucose uptake by normal rat skeletal muscle. Horm Metab Res. 2005;37(5):275–80.

26. Chaikomin R, Doran S, Jones KL, Feinle-Bisset C, O' Donovan D, Rayner CK, et al. Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects. Am J Physiol Endocrinol Metab. 2005 Sep;289(3): E504–7. Epub 2005.

27. Ekblad E, Sundler F. Distribution of pancreatic polypeptide and peptide YY. Peptides 2002;23(2):251–261. doi: 10.1016/S0196-9781(01)00601-5.

28. Batterham RL, Bloom SR. The Gut Hormone Peptide YY Regulates Appetite. Annals of the New York Academy of Sciences 2003;994(1):162–168. doi: 10.1111/j.1749-6632.2003.tb03176.x.

29. Eissele R, GÖke R, Willemer S, Harthus HP, Vermeer H, Arnold R, et al. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 1992;22(4):283–291. PMID: 1499644. doi: 10.1111/j.1365-2362.1992.tb01464.x.

30. Zac-Varghese S, Tan T, Bloom SR. Hormonal interactions between gut and brain. Discov Med 2010;10(55):543–52.

31. Kojima M, Kangawa K. Ghrelfrom gene to physiological function. Results Probl Cell Differ. 2010;50:185–205. doi: 10.1007/400_2009_28.

32. Estall JL, Drucker DJ. Glucagon-like peptide-2. Annu Rev Nutr. 2006;26:391–411.

33. Bose M, Teixeira J, Olivan B, Bawa B, Arias S, Machineni S, et al. Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery. J Diabetes 2010;2(1):47-55. PMID: 20676394. doi: 10.1111/j.1753-0407.2009.00064.x.

34. Shak JR, Roper J, Perez-Perez GI, Tseng C, Francois F, Gamagaris Z, et al. The Effect of Laparoscopic Gastric Banding Surgery on Plasma Levels of Appetite-Control, Insulinotropic, and Digestive Hormones. OBES SURG 2008;18(9):1089–1096. PMID: 18408980. doi: 10.1007/s11695-008-9454-6.

35. Guldstrand M, Ahrén B, Näslund E, Holst JJ, Adamson U. Dissociated incretin response to oral glucose at 1 year after re-strictive vs. malabsorptive bariatric surgery. Diabetes Obes Metab 2009;11(11):1027-1033. PMID: 19614945. doi: 10.1111/j.1463-1326.2009.01089.x.

36. Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001;50(4):707–9.

37. English PJ, Ghatei MA, Malik IA, Bloom SR, Wilding JPH. Food Fails to Suppress Ghrelin Levels in Obese Humans. The Journal of Clinical Endocrinology & Metabolism 2002;87(6):2984–2984. doi: 10.1210/jcem.87.6.8738.

38. Cummings DE. Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery.. Int J Obes (Lond) 2009;33 Suppl 1:1–33. PMID: 19363506. doi: 10.1038/ijo.2009.15.

39. Anderson B, Switzer NJ, Almamar A, Shi X, Birch DW, Karmali S. The Impact of Laparoscopic Sleeve Gastrectomy on Plasma Ghrelin Levels: a Systematic Review. OBES SURG 2013;23(9):1476–1480. PMID: 23794092. doi: 10.1007/s11695-013-0999-7.

40. Karamanakos SN, Vagenas K, Kalfarentzos F, Alexandrides TK. Weight Loss, Appetite Suppression, and Changes in Fasting and Postprandial Ghrelin and Peptide-YY Levels After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy. Annals of Surgery 2008;247(3):401–407. doi: 10.1097/SLA.0b013e318156f012.

41. Bohdjalian A, Langer FB, Shakeri-Leidenmühler S, Gfrerer L, Ludvik B, Zacherl J, et al. Sleeve Gastrectomy as Sole and Definitive Bariatric Procedure: 5-Year Results for Weight Loss and Ghrelin. OBES SURG 2010;20(5):535–540. PMID: 20094819. doi: 10.1007/s11695-009-0066-6.

42. Näslund E, Grybäck P, Hellström PM, Jacobsson H, Holst JJ, Theodorsson E, et al. L Gastrointestinal hormones and gastric emptying 20 years after jejunoileal bypass for massive obesity. Int J Obes Relat Metab Disord 1997:–5.

43. Lauritsen KB, Christensen KC, Stokholm KH. Gastric Inhibitory Polypeptide (GIP) Release and Incretin Effect after Oral Glucose in Obesity and after Jejunoileal Bypass. Scand J Gastroenterol 1980;15(4):489–495. PMID: 7001614. doi: 10.3109/00365528009181506.

44. Vincent RP, le Roux, CW. Changes in gut hormones after bariatric surgery. Clinical Endocrinology 2008;69(2):173–179. doi: 10.1111/j.1365-2265.2007.03164.x.

45. Kashyap SR, Gatmaitan P, Brethauer S, Schauer P. Bariatric surgery for type 2 diabetes: Weighing the impact for obese patients. Cleveland Clinic Journal of Medicine 2010;77(7):468–476. PMID: 20601620. doi: 10.3949/ccjm.77a.09135.

46. Salinari S, Bertuzzi A, Asnaghi S, Guidone C, Manco M, Mingrone G. First-Phase Insulin Secretion Restoration and Differential Response to Glucose Load Depending on the Route of Administration in Type 2 Diabetic Subjects After Bariatric Surgery. Diabetes Care 2008;32(3):375–380. PMID: 19033407. doi: 10.2337/dc08-1314.

47. Morínigo R, Casamitjana R, Moizé V, Lacy AM, Delgado S, Gomis R, et al. Short-term effects of gastric bypass surgery on circulating ghrelin levels. Obes Res 2004;12(7):1108–1116. PMID: 15292475. doi: 10.1038/oby.2004.139.

48. Garcia-Fuentes E, Garrido-Sanchez L, Garcia-Almeida JM, Garcia-Arnes J, Gallego-Perales JL, Rivas-Marin J, et al. Different Effect of Laparoscopic Roux-en-Y Gastric Bypass and Open Biliopancreatic Diversion of Scopinaro on Serum PYY and Ghrelin Levels. OBES SURG 2008;18(11):1424–1429. PMID: 18542849. doi: 10.1007/s11695-008-9560-5.

49. Mingrone G, Granato L, Valera-Mora E, Iaconelli A, Calvani MF, Bracaglia R, et al. Ultradian ghrelin pulsatility is disrupted in morbidly obese subjects after weight loss induced by malabsorptive bariatric surgery. Am J Clin Nutr 2006;83(5):1017–1024. PMID: 16685041.

50. Garb J, Welch G, Zagarins S, Kuhn J, Romanelli J. Bariatric Surgery for the Treatment of Morbid Obesity: A Meta-analysis of Weight Loss Outcomes for Laparoscopic Adjustable Gastric Banding and Laparoscopic Gastric Bypass. OBES SURG 2009;19(10):1447–1455. doi: 10.1007/s11695-009-9927-2.

51. Frühbeck G, Rotellar F, Hernández-Lizoain JL, Gil, M. Jesús, Gómez-Ambrosi J, Salvador J, et al. Fasting Plasma Ghrelin Concentrations 6 Months after Gastric Bypass are not Determined by Weight Loss or Changes in Insulinemia. Obes Surg 2004;14(9):1208–1215. doi: 10.1381/0960892042386904.