Metabesity in Women: Long-term Health Effects

Objective of the Review: To present the available data on the impact of obesity on woman’s health and quality of life.

Key Points. The term “metabesity” includes a range of conditions associated with obesity and its sequelae. From pathogenic point of view, it is an obesity-associated metabolic aberration: subacute inflammation, mitochondrial dysfunction, and changed gut microbiome. Together with a genetic component, the phenotypes of metabesity are mostly a result of sedentary lifestyle and unhealthy eating. Metabesity is associated with a number of both health- and life-threatening comorbidities, including arterial hypertension, cardiac failure, myocardial infraction, and stroke. Insulin resistance, hypertensive disease, advanced arteriosclerosis, dyslipidemia and fatty hepatosis are more frequent in obese people than in the general population. This literature overview presents a modern idea of the metabesity impact on the long-term health of a woman.

Conclusion. Recently, forecasting and prevention of diseases affecting the quality and duration of life have been attracting more and more interest. Taking into account the regular changes in the gender component of the population with age, obesity and its impact on the health of women from various age categories are of special interest. Obesity increases the risk and overall cancer mortality. Metabesity affects hormonal homoeostasis in the female body and increases the risk of degenerative conditions, including dementia. Taking into account the genetic component, the strategies to tackle metabesity, including a campaign against sedentary lifestyle and unhealthy eating, should be initiated since early childhood. Lifestyle modification is the only proven way to manage/prevent metabesity and associated diseases.

1. Mendrick D.L., Diehl A.M., Topor L.S., Dietert R.R. et al. Metabolic syndrome and associated diseases: from the bench to the clinic. Toxicol. Sci. 2018;162(1):36–42. DOI: 10.1093/toxsci/kfx233

2. Raza S.A., Sabir S.S., Ali K.B., Ali C.A. et al. Metabesity: expert panel recommendation for taking up the challenge by a multidisciplinary approach. J. Pak. Med. Assoc. 2020;70(8):1418–24. DOI: 10.5455/JPMA.56654

3. Gauthier B.R., Bermúdez-Silva F.J. Advances in genetics of regeneration in metabesity. Genes (Basel). 2019;10(5):383. DOI: 10.3390/genes10050383

4. Fall T., Ingelsson E. Genome-wide association studies of obesity and metabolic syndrome. Mol. Cell Endocrinol. 2014;382(1):740–57. DOI: 10.1016/j.mce.2012.08.018

5. Heard-Costa N., Zillikens M.C., Monda K.L., Johansson A. et al. NRXN3 is a novel locus for waist circumference: a genomewide association study from the CHARGE Consortium. PLoS Genet. 2009;5(6):e1000539. DOI: 10.1371/journal.pgen.1000539

6. Locke A.E., Kahali B., Berndt S.I., Justice A.E. et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197–206. DOI: 10.1038/nature14177

7. Albuquerque D., Nóbrega C., Manco L., Padez C. The contribution of genetics and environment to obesity. Br. Med. Bull. 2017;123(1):159–73. DOI: 10.1093/bmb/ldx022

8. Janssen I., Katzmarzyk P.T., Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch. Intern. Med. 2002;162(18):2074–9. DOI: 10.1001/archinte.162.18.2074

9. Staiano A.E., Broyles S.T., Gupta A.K., Katzmarzyk P.T. Ethnic and sex differences in visceral, subcutaneous, and total body fat in children and adolescents. Obesity (Silver Spring). 2013;21(6):1251–5. DOI: 10.1002/oby.20210

10. Owens S., Gutin B., Ferguson M., Allison J. et al. Visceral adipose tissue and cardiovascular risk factors in obese children. J. Pediatr. 1998;133(1):41–5. DOI: 10.1016/s0022-3476(98)70175-1

11. Koliaki C., Liatis S., Kokkinos A. Obesity and cardiovascular disease: revisiting an old relationship. Metabolism. 2019;92:98–107. DOI: 10.1016/j.metabol.2018.10.011

12. Wilson P.W.F., D'Agostino R.B., Sullivan L., Parise H. et al. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch. Intern. Med. 2002;162(16):1867–72. DOI: 10.1001/archinte.162.16.1867

13. Ortega F.B., Lavie C.J., Blair S.N. Obesity and cardiovascular disease. Circ. Res. 2016;118(11):1752–70. DOI: 10.1161/CIRCRESAHA.115.306883

14. Abdullah A., Wolfe R., Stoelwinder J.U., de Courten M. et al. The number of years lived with obesity and the risk of all-cause and cause-specific mortality. Int. J. Epidemiol. 2011;40(4):985–96. DOI: 10.1093/ije/dyr018

15. Wedell-Neergaard A.S., Krogh-Madsen R., Petersen G.L., Hansen Å.M. et al. Cardiorespiratory fitness and the metabolic syndrome: roles of inflammation and abdominal obesity. PLoS One. 2018;13(3):e0194991. DOI: 10.1371/journal.pone.0194991

16. Hainer V., Toplak H., Stich V. Fat or fit: what is more important? Diabetes Care. 2009;32(suppl.2):S392–7. DOI: 10.2337/dc09-S346

17. Rueda-Clausen C.F., Ogunleye A.A., Sharma A.M. Health benefits of long-term weight-loss maintenance. Annu. Rev. Nutr. 2015;35:475– 516. DOI: 10.1146/annurev-nutr-071714-034434

18. Ma C., Avenell A., Bolland M., Hudson J. et al. Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ. 2017;359:j4849. DOI: 10.1136/bmj.j4849

19. US Preventive Services Task Force; Bibbins-Domingo K., Grossman D.C., Curry S.J. et al. Statin use for the primary prevention of cardiovascular disease in adults: US preventive services task force recommendation statement. JAMA. 2016;316(19):1997–2007. DOI: 10.1001/jama.2016.15450

20. Wang S., Cai R., Yuan Y., Varghese Z. et al. Association between reductions in low-density lipoprotein cholesterol with statin therapy and the risk of new-onset diabetes: a meta-analysis. Sci. Rep. 2017;7:39982. DOI: 10.1038/srep39982

21. Orio F., Muscogiuri G., Nese C., Palomba S. et al. Obesity, type 2 diabetes mellitus and cardiovascular disease risk: an uptodate in the management of polycystic ovary syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 2016;207:214–19. DOI: 10.1016/j.ejogrb.2016.08.026

22. Colberg S.R., Sigal R.J., Yardley J.E., Riddell M.C. et al. Physical activity/exercise and diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2016;39(11):2065–79. DOI: 10.2337/dc16-1728

23. Kanwar P., Nelson J.E., Yates K., Kleiner D.E. et al. Association between metabolic syndrome and liver histology among NAFLD patients without diabetes. BMJ Open Gastroenterol. 2016;3(1):e000114. DOI: 10.1136/bmjgast-2016-000114

24. Han E., Lee Y.H. Non-alcoholic fatty liver disease: the emerging burden in cardiometabolic and renal diseases. Diabetes Metab. J. 2017;41(6):430–7. DOI: 10.4093/dmj.2017.41.6.430

25. Mokhtari Z., Gibson D.L., Hekmatdoost A. Nonalcoholic fatty liver disease, the gut microbiome, and diet. Adv. Nutr. 2017;8(2):240–52. DOI: 10.3945/an.116.013151

26. Allott E.H., Hursting S.D. Obesity and cancer: mechanistic insights from transdisciplinary studies. Endocr. Relat. Cancer. 2015;22(6):R365–86. DOI: 10.1530/ERC-15-0400

27. Avgerinos K.I., Spyrou N., Mantzoros C.S., Dalamaga M. Obesity and cancer risk: emerging biological mechanisms and perspectives. Metabolism. 2019;92:121–35. DOI: 10.1016/j.metabol.2018.11.001

28. Sung H., Siegel R.L., Rosenberg P.S., Jemal A. Emerging cancer trends among young adults in the USA: analysis of a populationbased cancer registry. Lancet Public Health. 2019;4(3):e137–47. DOI: 10.1016/S2468-2667(18)30267-6

29. Liu K., Zhang W., Dai Z., Wang M. et al. Association between body mass index and breast cancer risk: evidence based on a doseresponse meta-analysis. Cancer Manag. Res. 2018;10:143–51. DOI: 10.2147/CMAR.S144619

30. Devericks E.N., Carson M.S., McCullough L.E., Coleman M.F. et al. The obesity-breast cancer link: a multidisciplinary perspective. Cancer Metastasis Rev. 2022;41(3):607–25. DOI: 10.1007/s10555-022-10043-5

31. Linehan W.M., Ricketts C.J. The metabolic basis of kidney cancer. Semin. Cancer Biol. 2013;23(1):46–55. DOI: 10.1016/j.semcancer.2012.06.002

32. Fan Y.C., Chou C.C., You S.L., Sun C.A. et al. Impact of worsened metabolic syndrome on the risk of dementia: a nationwide cohort study. J. Am. Heart Assoc. 2017;6(9):e004749. DOI: 10.1161/JAHA.116.004749

33. Pourshahidi L.K. Vitamin D and obesity: current perspectives and future directions. Proc. Nutr. Soc. 2015;74(2):115–24. DOI: 10.1017/S0029665114001578

34. Grondhuis S.N., Aman M.G. Overweight and obesity in youth with developmental disabilities: a call to action. J. Intellect. Disabil. Res. 2014;58(9):787–99. DOI: 10.1111/jir.12090

35. Jing Y., Wu F., Li D., Yang L. et al. Metformin improves obesityassociated inflammation by altering macrophages polarization. Mol. Cell Endocrinol. 2018;461:256–64. DOI: 10.1016/j.mce.2017.09.025

36. Maniar K., Moideen A., Bhattacharyya R., Banerjee D. Metformin exerts anti-obesity effect via gut microbiome modulation in prediabetics. Med. Hypotheses. 2017;104:117–20. DOI: 10.1016/j.mehy.2017.06.001