МЕТАБОЛИЧЕСКИ ЗДОРОВОЕ ОЖИРЕНИЕ: ДЕФИНИЦИИ, ПРОТЕКТИВНЫЕ ФАКТОРЫ, КЛИНИЧЕСКАЯ ЗНАЧИМОСТЬ

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Ожирение – фактор риска сердечно-сосудистых заболеваний и сахарного диабета 2-го типа, тем не менее у  ряда больных ожирением кардиометаболические осложнения отсутствуют. Для определения этой группы пациентов в 1982 г. был предложен термин «метаболически здоровое ожирение» (МЗО). В настоящее время стандартных дефиниций МЗО не существует, сведения о  его распространенности крайне вариабельны. Механизмы, предопределяющие этот фенотип, остаются не ясными. Предположительно, сохранная чувствительность к  инсулину, высокий уровень физической активности и  генетические особенности лежат в  основе отличий МЗО от метаболически нездорового ожирения. Медленно прогрессирующее воспаление жировой ткани выступает ключевым патогенетическим фактором метаболических заболеваний. По сравнению с  метаболически нездоровым ожирением фенотип МЗО характеризуется более благоприятным профилем воспаления в жировой ткани, меньшим объемом висцеральных депо, менее выраженной инфильтрацией макрофагами, меньшим размером адипоцитов. Остается открытым вопрос о  стабильности фенотипа МЗО.

 Целью настоящего обзора является обсуждение данных современной литературы, отражающих характеристику фенотипа МЗО, его дефиниции, распространенность и  потенциально протективные факторы, предопределяющие метаболическое здоровье. Кроме того, обсуждается клиническая значимость выделения фенотипа МЗО.

Об авторах

Т. И. Романцова

Первый Московский государственный медицинский университет им. И.М. Сеченова

Автор, ответственный за переписку.
Email: romantsovatatiana@rambler.ru

Романцова Татьяна Ивановна – доктор медицинских наук, профессор кафедры эндокринологии

* 119991, г. Москва, ул. Трубецкая, 8/2, Российская Федерация. Тел.: +7 (499) 248 38 66. E-mail: romantsovatatiana@rambler.ru

Россия

Е. В. Островская

Первый Московский государственный медицинский университет им. И.М. Сеченова

Email: romantsovatatiana@rambler.ru

Островская Елена Владимировна – аспирант кафедры эндокринологии

Россия

Список литературы

  1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, AbuRmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81.
  2. World Health Organization Media Centre. Obesity and overweight. Fact sheet no 311. Geneva: World Health Organization; 2013.
  3. Primeau V, Coderre L, Karelis AD, Brochu M, Lavoie ME, Messier V, Sladek R, RabasaLhoret R. Characterizing the profile of obese patients who are metabolically healthy. Int J Obes (Lond). 2011;35(7):971–81.
  4. Blüher M. The distinction of metabolically ‘healthy’ from ‘unhealthy’ obese individuals. Curr Opin Lipidol. 2010;21(1):38–43.
  5. Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, Sowers MR. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999– 2004). Arch Intern Med. 2008;168(15):1617–24.
  6. Samocha-Bonet D, Chisholm DJ, Tonks K, Campbell LV, Greenfield JR. Insulinsensitive obesity in humans – a ‘favorable fat’ phenotype? Trends Endocrinol Metab. 2012;23(3):116–24.
  7. Alam I, Ng TP, Larbi A. Does inflammation determine whether obesity is metabolically healthy or unhealthy? The aging perspective. Mediators Inflamm. 2012;2012:456456.
  8. Sims EAH. Characterization of the syndromes of obesity. In: Brodoff BN, Bleicher SJ, editors. Diabetes Mellitus and Obesity. Baltimore: Williams and Wilkins; 1982. p. 219–26.
  9. Keys A. Overweight and the risk of heart attack and sudden death. In: Obesity in perspective. DHEW Publ. No. (NIH) 75–708. Washington, D.C.: U.S. Government Printing Office; 1973.
  10. Andres R. Effect of obesity on total mortality. Int J Obes. 1980;4(4):381–6.
  11. Aguilar-Salinas CA, García EG, Robles L, Riaño D, Ruiz-Gomez DG, García-Ulloa AC, Melgarejo MA, Zamora M, Guillen-Pineda LE, Mehta R, Canizales-Quinteros S, Tusie Luna MT, Gómez-Pérez FJ. High adiponectin concentrations are associated with the metabolically healthy obese phenotype. J Clin Endocrinol Metab. 2008;93(10):4075–9.
  12. Karelis AD, Brochu M, Rabasa-Lhoret R. Can we identify metabolically healthy but obese individuals (MHO)? Diabetes Metab. 2004;30(6):569–72.
  13. Meigs JB, Wilson PW, Fox CS, Vasan RS, Nathan DM, Sullivan LM, D’Agostino RB. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab. 2006;91(8):2906–12.
  14. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–97.
  15. Phillips CM. Metabolically healthy obesity: definitions, determinants and clinical implications. Rev Endocr Metab Disord. 2013;14(3):219–27.
  16. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5.
  17. Stefan N, Häring HU, Hu FB, Schulze MB. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 2013;1(2):152–62.
  18. Rey-López JP, de Rezende LF, Pastor-Valero M, Tess BH. The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used. Obes Rev. 2014;15(10):781–90.
  19. van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, Doiron D, Fischer K, Foco L, Gaye A, Gögele M, Heier M, Hiekkalinna T, Joensuu A, Newby C, Pang C, Partinen E, Reischl E, Schwienbacher C, Tammesoo ML, Swertz MA, Burton P, Ferretti V, Fortier I, Giepmans L, Harris JR, Hillege HL, Holmen J, Jula A, KootstraRos JE, Kvaløy K, Holmen TL, Männistö S, Metspalu A, Midthjell K, Murtagh MJ, Peters A, Pramstaller PP, Saaristo T, Salomaa V, Stolk RP, Uusitupa M, van der Harst P, van der Klauw MM, Waldenberger M, Perola M, Wolffenbuttel BH. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr Disord. 2014;14:9.
  20. Li S, Chen W, Srinivasan SR, Xu J, Berenson GS. Relation of childhood obesity/cardiometabolic phenotypes to adult cardiometabolic profile: the Bogalusa Heart Study. Am J Epidemiol. 2012;176 Suppl 7:S142–9.
  21. Rhee EJ, Lee MK, Kim JD, Jeon WS, Bae JC, Park SE, Park CY, Oh KW, Park SW, Lee WY. Metabolic health is a more important determinant for diabetes development than simple obesity: a 4-year retrospective longitudinal study. PLoS One. 2014;9(5):e98369.
  22. Al Suwaidi J. Is there an increased cardiovascular risk in metabolically healthy obese individuals? Lessons from the HUNT (Nord-Trøndelag Health) study. Glob Cardiol Sci Pract. 2014;2014(2):44–7.
  23. Meigs JB, Wilson PW, Fox CS, Vasan RS, Nathan DM, Sullivan LM, D’Agostino RB. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab. 2006;91(8): 2906–12.
  24. Luo D, Liu F, Li X, Yin D, Lin Z, Liu H, Hou X, Wang C, Jia W. Comparison of the effect of ‘metabolically healthy but obese’ and ‘metabolically abnormal but not obese’ phenotypes on development of diabetes and cardiovascular disease in Chinese. Endocrine. 2014;9:23–33.
  25. Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab. 2012;97(7):2482–8.
  26. Calori G, Lattuada G, Piemonti L, Garancini MP, Ragogna F, Villa M, Mannino S, Crosignani P, Bosi E, Luzi L, Ruotolo G, Perseghin G. Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the Cremona Study. Diabetes Care. 2011;34(1):210–5.
  27. Appleton SL, Seaborn CJ, Visvanathan R, Hill CL, Gill TK, Taylor AW, Adams RJ; North West Adelaide Health Study Team. Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: a cohort study. Diabetes Care. 2013;36(8): 2388–94.
  28. Soriguer F, Gutiérrez-Repiso C, Rubio-Martín E, García-Fuentes E, Almaraz MC, Colomo N, Esteva de Antonio I, de Adana MS, Chaves FJ, Morcillo S, Valdés S, Rojo-Martínez G. Metabolically healthy but obese, a matter of time? Findings from the prospective Pizarra study. J Clin Endocrinol Metab. 2013;98(6):2318-25.
  29. Bell JA, Kivimaki M, Hamer M. Metabolically healthy obesity and risk of incident type 2 diabetes: a meta-analysis of prospective cohort studies. Obes Rev. 2014;15(6): 504–15.
  30. Aung K, Lorenzo C, Hinojosa MA, Haffner SM. Risk of developing diabetes and cardiovascular disease in metabolically unhealthy normalweight and metabolically healthy obese individuals. J Clin Endocrinol Metab. 2014;99(2):462–8.
  31. Hinnouho GM, Czernichow S, Dugravot A, Batty GD, Kivimaki M, Singh-Manoux A. Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care. 2013;36(8): 2294–300.
  32. Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions?: A systematic review and meta-analysis. Ann Intern Med. 2013;159(11):758–69.
  33. Roberson LL, Aneni EC, Maziak W, Agatston A, Feldman T, Rouseff M, Tran T, Blaha MJ, Santos RD, Sposito A, Al-Mallah MH, Blankstein R, Budoff MJ, Nasir K. Beyond BMI: The “Metabolically healthy obese” phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality – a systematic review. BMC Public Health. 2014;14:14.
  34. Brown RE, Kuk JL. Consequences of obesity and weight loss: a devil’s advocate position. Obes Rev. 2015;16(1):77–87.
  35. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309(1):71–82.
  36. Samocha-Bonet D, Dixit VD, Kahn CR, Leibel RL, Lin X, Nieuwdorp M, Pietiläinen KH, Rabasa-Lhoret R, Roden M, Scherer PE, Klein S, Ravussin E. Metabolically healthy and unhealthy obese – the 2013 Stock Conference report. Obes Rev. 2014;15(9):697–708.
  37. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156(1– 2):20–44.
  38. Nakamura K, Fuster JJ, Walsh K. Adipokines: a link between obesity and cardiovascular disease. J Cardiol. 2014;63(4):250–9.
  39. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121(6):2094–101.
  40. Badoud F, Perreault M, Zulyniak MA, Mutch DM. Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals. FASEB J. 2014 Nov 19. pii: fj.14-263913.
  41. Khan UI, Ogorodnikova AD, Xu L, Wang D, Wassertheil-Smoller S, Ho GY, Sowers MF, Rajpathak SN, Allison MA, Mackey RH, Vitolins MZ, Manson JE, Wildman RP. The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women’s Health Initiative Observational Study. Obesity (Silver Spring). 2014;22(3):786–94.
  42. Stefan N, Häring HU. Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans. Nat Med. 2013;19(4):394–5.
  43. Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M, Abate N, Zhang BB, Bonaldo P, Chua S, Scherer PE. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol. 2009;29(6):1575–91.
  44. Primeau V, Coderre L, Karelis AD, Brochu M, Lavoie ME, Messier V, Sladek R, RabasaLhoret R. Characterizing the profile of obese patients who are metabolically healthy. Int J Obes (Lond). 2011;35(7):971–81.
  45. Ogorodnikova AD, Khan UI, McGinn AP, Zeb I, Budoff MJ, Harman SM, Miller VM, Brinton EA, Manson JE, Hodis HN, Merriam GR, Cedars MI, Taylor HS, Naftolin F, Lobo RA, Santoro N, Wildman RP. Ectopic fat and adipokines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study. Obesity (Silver Spring). 2013;21(8): 1726–33.
  46. Navarro E, Funtikova AN, Fíto M, Schröder H. Can metabolically healthy obesity be explained by diet, genetics, and inflammation? Mol Nutr Food Res. 2015;59(1):75–93.
  47. Plourde G, Karelis AD. Current issues in the identification and treatment of metabolically healthy but obese individuals. Nutr Metab Cardiovasc Dis. 2014;24(5):455–9.
  48. Phillips CM, Dillon C, Harrington JM, McCarthy VJ, Kearney PM, Fitzgerald AP, Perry IJ. Defining metabolically healthy obesity: role of dietary and lifestyle factors. PLoS One. 2013;8(10):e76188. 49. Bell JA, Kivimaki M, Batty GD, Hamer M. Metabolically healthy obesity: what is the role of sedentary behaviour? Prev Med. 2014;62:35–7.
  49. Velho S, Paccaud F, Waeber G, Vollenweider P, Marques-Vidal P. Metabolically healthy obesity: different prevalences using different criteria. Eur J Clin Nutr. 2010;64(10):1043–51.
  50. Camhi SM, Waring ME, Sisson SB, Hayman LL, Must A. Physical activity and screen time in metabolically healthy obese phenotypes in adolescents and adults. J Obes. 2013;2013:984613.
  51. Ortega FB, Lee DC, Katzmarzyk PT, Ruiz JR, Sui X, Church TS, Blair SN. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. Eur Heart J. 2013;34(5):389–97.
  52. Telle-Hansen VH, Halvorsen B, Dalen KT, Narverud I, Wesseltoft-Rao N, Granlund L, Ulven SM, Holven KB. Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype. Genes Nutr. 2013;8(4):425–34.
  53. Jais A, Einwallner E, Sharif O, Gossens K, Lu TT, Soyal SM, Medgyesi D, Neureiter D, PaierPourani J, Dalgaard K, Duvigneau JC, LindroosChristensen J, Zapf TC, Amann S, Saluzzo S, Jantscher F, Stiedl P, Todoric J, Martins R, Oberkofler H, Müller S, Hauser-Kronberger C, Kenner L, Casanova E, Sutterlüty-Fall H, Bilban M, Miller K, Kozlov AV, Krempler F, Knapp S, Lumeng CN, Patsch W, Wagner O, Pospisilik JA, Esterbauer H. Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man. Cell. 2014;158(1): 25–40.
  54. Xu XJ, Gauthier MS, Hess DT, Apovian CM, Cacicedo JM, Gokce N, Farb M, Valentine RJ, Ruderman NB. Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue. J Lipid Res. 2012;53(4):792–801.
  55. Hardy OT, Perugini RA, Nicoloro SM, GallagherDorval K, Puri V, Straubhaar J, Czech MP. Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity. Surg Obes Relat Dis. 2011;7(1):60–7.
  56. Mathur SK, Jain P, Mathur P, Punjabi P, Agarwal A, Sharma A. Transcriptomic analysis of visceral adipose from healthy and diabetic obese subjects. Indian J Endocrinol Metab. 2013;17(3):446–50.
  57. Naukkarinen J, Heinonen S, Hakkarainen A, Lundbom J, Vuolteenaho K, Saarinen L, Hautaniemi S, Rodriguez A, Frühbeck G, Pajunen P, Hyötyläinen T, Orešič M, Moilanen E, Suomalainen A, Lundbom N, Kaprio J, Rissanen A, Pietiläinen KH. Characterising metabolically healthy obesity in weightdiscordant monozygotic twins. Diabetologia. 2014;57(1):167–76.
  58. Janiszewski PM, Ross R. Effects of weight loss among metabolically healthy obese men and women. Diabetes Care. 2010;33(9):1957–9.
  59. Sesti G, Folli F, Perego L, Hribal ML, Pontiroli AE. Effects of weight loss in metabolically healthy obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet. PLoS One. 2011;6(3):e17737.
  60. Dalzill C, Nigam A, Juneau M, Guilbeault V, Latour E, Mauriège P, Gayda M. Intensive lifestyle intervention improves cardiometabolic and exercise parameters in metabolically healthy obese and metabolically unhealthy obese individuals. Can J Cardiol. 2014;30(4):434–40.
  61. Kantartzis K, Machann J, Schick F, Rittig K, Machicao F, Fritsche A, Häring HU, Stefan N. Effects of a lifestyle intervention in metabolically benign and malign obesity. Diabetologia. 2011;54(4):864–8.
  62. Arsenault BJ, Côté M, Cartier A, Lemieux I, Després JP, Ross R, Earnest CP, Blair SN, Church TS. Effect of exercise training on cardiometabolic risk markers among sedentary, but metabolically healthy overweight or obese post-menopausal women with elevated blood pressure. Atherosclerosis. 2009;207(2):530–3.
  63. Karelis AD, Messier V, Brochu M, RabasaLhoret R. Metabolically healthy but obese women: effect of an energy-restricted diet. Diabetologia. 2008;51(9):1752–4.
  64. Williamson DF, Pamuk E, Thun M, Flanders D, Byers T, Heath C. Prospective study of intentional weight loss and mortality in overweight white men aged 40-64 years. Am J Epidemiol. 1999;149(6):491–503.
  65. Sørensen TI, Rissanen A, Korkeila M, Kaprio J. Intention to lose weight, weight changes, and 18-y mortality in overweight individuals without co-morbidities. PLoS Med. 2005;2(6):e171.
  66. Берштейн ЛМ, Коваленко ИГ. «Метаболически здоровые» лица с ожирением и метаболические признаки ожирения у лиц с нормальной массой тела: что за этим стоит? Проблемы эндокринологии. 2010;3:47–51. (Bershteyn LM, Kovalenko IG. [Metabolically healthy obese subjects and metabolic signs of obesity in subjects with normal body weight: what is behind?]. Problemy endokrinologii. 2010;3:47–51. Russian).
  67. Berstein LM. Dark and light side of obesity: mortality of metabolically healthy obese people. Expert Rev Endocrinol Metab. 2012;7(6):629–32. 69.Denis GV, Obin MS. ‘Metabolically healthy obesity’: origins and implications. Mol Aspects Med. 2013;34(1):59–70.

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