Current state of the obesity research: genetic aspects, the role of microbiome, and susceptibility to COVID-19
https://doi.org/10.14341/probl12775
Abstract
Obesity affects over 700 million people worldwide and its prevalence keeps growing steadily. The problem is particularly relevant due to the increased risk of COVID-19 complications and mortality in obese patients. Obesity prevalence increase is often associated with the influence of environmental and behavioural factors, leading to stigmatization of people with obesity due to beliefs that their problems are caused by poor lifestyle choices. However, hereditary predisposition to obesity has been established, likely polygenic in nature. Morbid obesity can result from rare mutations having a significant effect on energy metabolism and fat deposition, but the majority of patients does not present with monogenic forms. Microbiome low diversity significantly correlates with metabolic disorders (inflammation, insulin resistance), and the success of weight loss (bariatric) surgery. However, data on the long-term consequences of bariatric surgery and changes in the microbiome composition and genetic diversity before and after surgery are currently lacking. In this review, we summarize the results of studies of the genetic characteristics of obesity patients, molecular mechanisms of obesity, contributing to the unfavourable course of coronavirus infection, and the evolution of their microbiome during bariatric surgery, elucidating the mechanisms of disease development and creating opportunities to identify potential new treatment targets and design effective personalized approaches for the diagnosis, management, and prevention of obesity.
About the Authors
Ya. R. TimashevaRussian Federation
Yanina R. Timasheva, MD, PhD
eLibrary SPIN: 9962-8494
Ufa
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.
Zh. R. Balkhiyarova
Russian Federation
Zhanna R. Balkhiyarova, MD, PhD
eLibrary SPIN: 3176-3244
Ufa;
Guildford, United Kingdom
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.
O. V. Kochetova
Russian Federation
Olga V. Kochetova, PhD
eLibrary SPIN: 3461-3952
Ufa
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.
References
1. World Health Organization. Preventing and Managing the Global Epidemic: Report on a WHO Consultation (WHO Technical Report Series 894). Geneva, Switzerland: World Health Organization; 2000.
2. Kontsevaya A, Shalnova S, Deev A, et al. Overweight and Obesity in the Russian Population: Prevalence in Adults and Association with Socioeconomic Parameters and Cardiovascular Risk Factors. Obes Facts. 2019;12(1):103-114. doi: https://doi.org/10.1159/000493885
3. Hales CM, Carroll MD, Fryar CD, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief. 2020;360:1-8.
4. Blüher M. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance? Clin Sci. 2016;130(18):1603-1614. doi: https://doi.org/10.1042/CS20160005
5. Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6-10. doi: https://doi.org/10.1016/j.metabol.2018.09.005
6. Ladabaum U, Mannalithara A, Myer PA, Singh G. Obesity, Abdominal Obesity, Physical Activity, and Caloric Intake in US Adults: 1988 to 2010. Am J Med. 2014;127(8):717-727.e12. doi: https://doi.org/10.1016/j.amjmed.2014.02.026
7. Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804-814. doi: https://doi.org/10.1016/S0140-6736(11)60813-1
8. Katzmarzyk PT, Pérusse L, Rao D, et al. Familial risk of overweight and obesity in the Canadian population using the WHO/NIH criteria. Obesity research. 2000;8(2):194-197. doi: https://doi.org/10.1038/oby.2000.21
9. Koeppen-Schomerus G, Wardle J, Plomin R. A genetic analysis of weight and overweight in 4-year-old twin pairs. International Journal of Obesity. 2001;25(6):838-844. doi: https://doi.org/10.1038/sj.ijo.0801589
10. Pietiläinen KH, Kaprio J, Rissanen A, et al. Distribution and heritability of BMI in Finnish adolescents aged 16 y and 17 y: A study of 4884 twins and 2509 singletons. International Journal of Obesity. 1999;23(2):107-115. doi: https://doi.org/10.1038/sj.ijo.0800767
11. Allison DB, Kaprio J, Korkeila M, et al. The heritability of body mass index among an international sample of monozygotic twins reared apart. International Journal of Obesity. 1996;20(6):501-506.
12. Feinleib M, Garrison RJ, Fabsitz R, et al. The NHLBI twin study of cardiovascular disease risk factors: methodology and summary of results. Am J Epidemiol. 1977;106(4):284-285. doi: https://doi.org/10.1093/oxfordjournals.aje.a112464
13. Stunkard AJ, Foch TT, Hrubec Z. A twin study of human obesity. JAMA. 1986;256(1):51-54. doi: https://doi.org/10.1001/jama.1986.03380010055024
14. Stunkard AJ, Harris JR, Pedersen NL, et al. The BodyMass Index of Twins Who Have Been Reared Apart. New England Journal of Medicine. 1990;322(21):1483-1487. doi: https://doi.org/10.1056/Nejm199005243222102
15. Fesinmeyer MD, North KE, Ritchie MD, et al. Genetic Risk Factors for BMI and Obesity in an Ethnically Diverse Population: Results from the Population Architecture Using Genomics and Epidemiology (PAGE) Study. Obesity. 2013;21(4):835-846. doi: https://doi.org/10.1002/oby.20268
16. Rohde K, Keller M, la Cour Poulsen L, et al. Genetics and epigenetics in obesity. Metabolism. 2019;92:37-50. doi: https://doi.org/10.1016/j.metabol.2018.10.007
17. Singh RK, Kumar P, Mahalingam K. Molecular genetics of human obesity: A comprehensive review. C R Biol. 2017;340(2):87-108. doi: https://doi.org/10.1016/j.crvi.2016.11.007
18. Kaur Y, de Souza RJ, Gibson WT, et al. A systematic review of genetic syndromes with obesity. Obes Rev. 2017;18(6):603-634. doi: https://doi.org/10.1111/obr.12531
19. Forsythe E, Kenny J, Bacchelli C, Beales PL. Managing Bardet–Biedl Syndrome — Now and in the Future. Front Pediatr. 2018;6. doi: https://doi.org/10.3389/fped.2018.00023
20. Bonnefond A, Raimondo A, Stutzmann F, et al. Loss-of-function mutations in SIM1 contribute to obesity and Prader-Willi–like features. The Journal of clinical investigation. 2013;123(7):3037-3041. doi: https://doi.org/10.1172/JCI68035
21. Desch L, Marle N, Mosca-Boidron A-L, et al. 6q16.3q23.3 duplication associated with Prader-Willi-like syndrome. Mol Cytogenet. 2015;8(1):42. doi: https://doi.org/10.1186/s13039-015-0151-6
22. Martinez-Cerdeno V, Lechpammer M, Noctor S, et al. FMR1 premutation with Prader-Willi phenotype and fragile X-associated tremor/ataxia syndrome. Clin Case Rep. 2017;5(5):625-629. doi: https://doi.org/10.1002/ccr3.834
23. Pigeyre M, Yazdi FT, Kaur Y, et al. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. Clin Sci (Lond). 2016;130(12):943-986. doi: https://doi.org/10.1042/CS20160136
24. Saeed S, Arslan M, Froguel P. Genetics of Obesity in Consanguineous Populations: Toward Precision Medicine and the Discovery of Novel Obesity Genes. Obesity (Silver Spring). 2018;26(3):474-484. doi: https://doi.org/10.1002/oby.22064
25. Ingelsson E, McCarthy MI. Human Genetics of Obesity and Type 2 Diabetes Mellitus: Past, Present, and Future. Circ Genom Precis Med. 2018;11(6):e002090. doi: https://doi.org/10.1161/CIRCGEN.118.002090
26. Choquet H, Meyre D. Molecular basis of obesity: current status and future prospects. Curr Genomics. 2011;12(3):154-168. doi: https://doi.org/10.2174/138920211795677921
27. Huvenne H, Dubern B, Clement K, et al. Rare Genetic Forms of Obesity: Clinical Approach and Current Treatments in 2016. Obes Facts. 2016;9(3):158-173. doi: https://doi.org/10.1159/000445061
28. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425-432. doi: https://doi.org/10.1038/372425a0
29. Morton GJ, Meek TH, Schwartz MW. Neurobiology of food intake in health and disease. Nat Rev Neurosci. 2014;15(6):367-378. doi: https://doi.org/10.1038/nrn3745
30. Licinio J, Caglayan S, Ozata M, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci U S A. 2004;101(13):4531-4536. doi: https://doi.org/10.1073/pnas.0308767101
31. Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085-1095. doi: https://doi.org/10.1056/NEJMoa022050
32. Krude H, Biebermann H, Luck W, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19(2):155-157. doi: https://doi.org/10.1038/509
33. Vaisse C, Clement K, Durand E, et al. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest. 2000;106(2):253-262. doi: https://doi.org/10.1172/JCI9238
34. Pritchard LE, Turnbull AV, White A. Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol. 2002;172(3):411-421. doi: https://doi.org/10.1677/joe.0.1720411
35. O’Rahilly S, Gray H, Humphreys PJ, et al. Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med. 1995;333(21):1386-1390. doi: https://doi.org/10.1056/NEJM199511233332104
36. Jackson RS, Creemers JW, Ohagi S, et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet. 1997;16(3):303-306. doi: https://doi.org/10.1038/ng0797-303
37. Saeed S, Bonnefond A, Tamanini F, et al. Loss-of-function mutations in ADCY3 cause monogenic severe obesity. Nature Genetics. 2018;50(2):175-179. doi: https://doi.org/10.1038/s41588-017-0023-6
38. Grarup N, Moltke I, Andersen MK, et al. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nat Genet. 2018;50(2):172-174. doi: https://doi.org/10.1038/s41588-017-0022-7
39. Ramachandrappa S, Raimondo A, Cali AM, et al. Rare variants in single-minded 1 (SIM1) are associated with severe obesity. J Clin Invest. 2013;123(7):3042-3050. doi: https://doi.org/10.1172/JCI68016
40. Holder JL Jr, Butte NF, Zinn AR. Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Human molecular genetics. 2000;9(1):101-108. doi: https://doi.org/10.1093/hmg/9.1.101
41. Chan LF, Webb TR, Chung TT, et al. MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc Natl Acad Sci U S A. 2009;106(15):6146-6151. doi: https://doi.org/10.1073/pnas.0809918106
42. Baron M, Maillet J, Huyvaert M, et al. Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension. Nat Med. 2019;25(11):1733-1738. doi: https://doi.org/10.1038/s41591-019-0622-0
43. Sebag JA, Zhang C, Hinkle PM, et al. Developmental control of the melanocortin-4 receptor by MRAP2 proteins in zebrafish. Science. 2013;341(6143):278-281. doi: https://doi.org/10.1126/science.1232995
44. Baron M, Froguel P, Bonnefond A. Du nouveau dans la génétique des formes monogéniques d’obésité et son impact pour mieux en comprendre la physiopathologie. Med Sci (Paris). 2020;36(10):859-865. doi: https://doi.org/10.1051/medsci/2020156
45. Yeo GS, Connie Hung CC, Rochford J, et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci. 2004;7(11):1187-1189. doi: https://doi.org/10.1038/nn1336
46. Gray J, Yeo GS, Cox JJ, et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes. 2006;55(12):3366-3371. doi: https://doi.org/10.2337/db06-0550
47. Yengo L, Sidorenko J, Kemper KE, et al. Meta-analysis of genome-wide association studies for height and body mass index in ~ 700000 individuals of European ancestry. Human molecular genetics. 2018;27(20):3641-3649. doi: https://doi.org/10.1093/hmg/ddy271
48. Tyrrell J, Wood AR, Ames RM, et al. Gene–obesogenic environment interactions in the UK Biobank study. International Journal of Epidemiology. 2017;46(2):559-575. doi: https://doi.org/10.1093/ije/dyw337
49. Goodarzi MO. Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes & Endocrinology. 2018;6(3):223-236. doi: https://doi.org/10.1016/S2213-8587(17)30200-0
50. Barres R, Kirchner H, Rasmussen M, et al. Weight loss after gastric bypass surgery in human obesity remodels promoter methylation. Cell Rep. 2013;3(4):1020-1027. doi: https://doi.org/10.1016/j.celrep.2013.03.018
51. Keller M, Hopp L, Liu X, et al. Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity. Mol Metab. 2017;6(1):86-100. doi: https://doi.org/10.1016/j.molmet.2016.11.003
52. Nilsson E, Jansson PA, Perfilyev A, et al. Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes. 2014;63(9):2962-2976. doi: https://doi.org/10.2337/db13-1459
53. Wahl S, Drong A, Lehne B, et al. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature. 2017;541(7635):81-86. doi: https://doi.org/10.1038/nature20784
54. Su L.-N, Wang Y-B, Wnag C-G, et al. Network analysis identifies common genes associated with obesity in six obesity-related diseases. Journal of Zhejiang University-SCIENCE B. 2017;18(8):727-732. doi: https://doi.org/10.1631/jzus.B1600454
55. Benzinou M, Creemers JW, Choquet H, et al. Common nonsynonymous variants in PCSK1 confer risk of obesity. Nature genetics. 2008;40(8):943. doi: https://doi.org/10.1038/ng.177
56. Choquet H, Kasberger J, Hamidovic A, et al. Contribution of common PCSK1 genetic variants to obesity in 8,359 subjects from multi-ethnic American population. PLoS One. 2013;8(2):e57857. doi: https://doi.org/10.1371/journal.pone.0057857
57. Rouskas K, Kouvatsi A, Paletas K, et al. Common variants in FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 show evidence of association with adult obesity in the Greek population. Obesity. 2012;20(2):389-395. doi: https://doi.org/10.1038/oby.2011.177
58. Loos RJ, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008;40(6):768-775. doi: https://doi.org/10.1038/ng.140
59. Claussnitzer M, Dankel SN, Kim KH, et al. FTO obesity variant circuitry and adipocyte browning in humans. New England Journal of Medicine. 2015;373(10):895-907. doi: https://doi.org/10.1056/NEJMoa1502214
60. Smemo S, Tena JJ, Kim K-H, et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature. 2014;507(7492):371-375. doi: https://doi.org/10.1038/nature13138
61. Lilenfeld LR, Kaye WH, Greeno CG, et al. A controlled family study of anorexia nervosa and bulimia nervosa: psychiatric disorders in first-degree relatives and effects of proband comorbidity. Arch Gen Psychiatry. 1998;55(7):603-610. doi: https://doi.org/10.1001/archpsyc.55.7.603
62. Strober M, Freeman R, Lampert C, et al. Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes. Am J Psychiatry. 2000;157(3):393-401. doi: https://doi.org/10.1176/appi.ajp.157.3.393
63. Thornton LM, Mazzeo SE, Bulik CM. The Heritability of Eating Disorders: Methods and Current Findings. In: Current Topics in Behavioral Neurosciences. ; 2010:141-156. doi: https://doi.org/10.1007/7854_2010_91
64. Elks CE, den Hoed M, Zhao JH, et al. Variability in the heritability of body mass index: a systematic review and meta-regression. Front Endocrinol (Lausanne). 2012;3:29. doi: https://doi.org/10.3389/fendo.2012.00029
65. Kendler KS, MacLean C, Neale M, et al. The genetic epidemiology of bulimia nervosa. American Journal of Psychiatry. 1991;148(12):1627-1637. doi: https://doi.org/10.1176/ajp.148.12.1627
66. Llewellyn C, Wardle J, Behavioral susceptibility to obesity: gene — environment interplay in the development of weight. Physiology & Behavior. 2015;152:494-501. doi: https://doi.org/10.1016/j.physbeh.2015.07.006
67. Llewellyn CH, Fildes A, Behavioural Susceptibility Theory: Professor Jane Wardle and the Role of Appetite in Genetic Risk of Obesity. Curr Obes Rep. 2017;6(1):38-45. doi: https://doi.org/10.1007/s13679-017-0247-x
68. Herle M, Smith AD, Kininmonth A, Llewellyn C. The Role of Eating Behaviours in Genetic Susceptibility to Obesity. Curr Obes Rep. 2020;9(4):512-521. doi: https://doi.org/10.1007/s13679-020-00402-0
69. Nicoletti CF, Delfino HBP, Ferreira FC, et al. Role of eating disorders-related polymorphisms in obesity pathophysiology. Rev Endocr Metab Disord. 2019;20(1):115-125. doi: https://doi.org/10.1007/s11154-019-09489-w
70. Masip G, Silventoinen K, Keski-Rahkonen A, et al. The genetic architecture of the association between eating behaviors and obesity: combining genetic twin modeling and polygenic risk scores. Am J Clin Nutr. 2020;112(4):956-966. doi: https://doi.org/10.1093/ajcn/nqaa181
71. Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197-401. doi: https://doi.org/10.1038/nature14177
72. Timshel PN, Thompson JJ, Pers TH. Genetic mapping of etiologic brain cell types for obesity. Elife. 2020;9:e55851. doi: https://doi.org/10.7554/eLife.55851
73. Wabitsch M, Funcke JB, Lennerz B, et al. Biologically inactive leptin and early-onset extreme obesity. N Engl J Med. 2015;372(1):48-54. doi: https://doi.org/10.1056/NEJMoa1406653
74. Santos JL, Cortés VA. Eating behaviour in contrasting adiposity phenotypes: Monogenic obesity and congenital generalized lipodystrophy. Obes Rev. 2021;22(1). doi: https://doi.org/10.1111/obr.13114
75. Paz-Filho G, Mastronardi CA, Licinio J. Leptin treatment: facts and expectations. Metabolism. 2015;64(1):146-156. doi: https://doi.org/10.1016/j.metabol.2014.07.014
76. Lu X-Y. The leptin hypothesis of depression: a potential link between mood disorders and obesity? Current opinion in pharmacology. 2007;7(6):648-652. doi: https://doi.org/10.1016/j.coph.2007.10.010
77. Domingos AI, Vaynshteyn J, Voss HU, et al. Leptin regulates the reward value of nutrient. Nature Neuroscience. 2011;14(12):1562-1568. doi: https://doi.org/10.1038/nn.2977
78. Yoshida R, Noguchi K, Shigemura N, et al. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds. Diabetes. 2015;64(11):3751-3762. doi: https://doi.org/10.2337/db14-1462
79. Rohde K, Keller M, Horstmann A, et al. Role of genetic variants in ADIPOQ in human eating behavior. Genes & Nutrition. 2014;10(1):1. doi: https://doi.org/10.1007/s12263-014-0449-8
80. Ma W, Huang T, Heianza Y, et al. Genetic Variations of Circulating Adiponectin Levels Modulate Changes in Appetite in Response to Weight-Loss Diets. J Clin Endocrinol Metab. 2017;102(1):316-325. doi: https://doi.org/10.1210/jc.2016-2909
81. Khalil RB, El Hachem C. Adiponectin in eating disorders. Eat Weight Disord. 2014;19(1):3-10. doi: https://doi.org/10.1007/s40519-013-0094-z
82. Kubota N, Yano W, Kubota T, et al. Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab. 2007;6(1):55-68. doi: https://doi.org/10.1016/j.cmet.2007.06.003
83. Bravo C, Cataldo LR, Galgani J, et al. Leptin/Adiponectin Ratios Using Either Total Or High-Molecular-Weight Adiponectin as Biomarkers of Systemic Insulin Sensitivity in Normoglycemic Women. J Diabetes Res. 2017;2017:1-11. doi: https://doi.org/10.1155/2017/9031079
84. Vasseur F, Meyre D, Froguel P. Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies. Expert Rev Mol Med. 2006;8(27):1-12. doi: https://doi.org/10.1017/S1462399406000147
85. Savage DC. Microbial ecology of the gastrointestinal tract. Annual review of microbiology. 1977;31(1):107-133. doi: https://doi.org/10.1146/annurev.mi.31.100177.000543
86. Tseng C-H, Wu C-Y. The gut microbiome in obesity. Journal of the Formosan Medical Association. 2019;118:S3-S9. doi: https://doi.org/10.1016/j.jfma.2018.07.009
87. Sender R, Fuchs S, Milo R. Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell. 2016;164(3):337-340. doi: https://doi.org/10.1016/j.cell.2016.01.013
88. Krautkramer KA, Fan J, Bäckhed F. Gut microbial metabolites as multi-kingdom intermediates. Nature Reviews Microbiology. 2021;19(2):77-94. doi: https://doi.org/10.1038/s41579-020-0438-4
89. Meijnikman AS, Gerdes VE, Nieuwdorp M, et al. Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans. Endocrine Reviews. 2018;39(2):133-153. doi: https://doi.org/10.1210/er.2017-00192
90. Ley RE, Turnbaugh PJ, Klein S, et al. Human gut microbes associated with obesity. Nature. 2006;444(7122):1022-1023. doi: https://doi.org/10.1038/4441022a
91. Zhao L. The gut microbiota and obesity: from correlation to causality. Nature Reviews Microbiology. 2013;11(9):639-647. doi: https://doi.org/10.1038/nrmicro3089
92. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480-484. doi: https://doi.org/10.1038/nature07540
93. Bäckhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences. 2004;101(44):15718-15723. doi: https://doi.org/10.1073/pnas.0407076101
94. Ley RE, Bäckhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences. 2005;102(31):11070-11075. doi: https://doi.org/10.1073/pnas.0504978102
95. Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027. doi: https://doi.org/10.1038/nature05414
96. Turpin W, Espin-Garcia O, Xu W, et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nature Genetics. 2016;48(11):1413-1417. doi: https://doi.org/10.1038/ng.3693
97. Goodrich Julia K, Waters Jillian L, Poole Angela C, et al. Human Genetics Shape the Gut Microbiome. Cell. 2014;159(4):789-799. doi: https://doi.org/https://doi.org/10.1016/j.cell.2014.09.053
98. Bonder MJ, Kurilshikov A, Tigchelaar EF, et al. The effect of host genetics on the gut microbiome. Nat Genet. 2016;48(11):1407-1412. doi: https://doi.org/10.1038/ng.3663
99. Crost EH, Le Gall G, Laverde-Gomez JA, et al. Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates. Front Microbiol. 2018;9:2558. doi: https://doi.org/10.3389/fmicb.2018.02558
100. Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet. 2021;53(2):156-165. doi: https://doi.org/10.1038/s41588-020-00763-1
101. Yoshii K, Hosomi K, Sawane K, et al. Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity. Front Nutr. 2019;6:48. doi: https://doi.org/10.3389/fnut.2019.00048
102. Rowley CA, Kendall MM. To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions. PLoS pathogens. 2019;15(1):e1007479-e1007479. doi: https://doi.org/10.1371/journal.ppat.1007479
103. Rung J, Cauchi S, Albrechtsen A, et al. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet. 2009;41(10):1110-1115. doi: https://doi.org/10.1038/ng.443
104. Liu TC, Kern JT, Jain U, et al. Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation. Cell Host Microbe. 2021;29(6):988-1001. doi: https://doi.org/10.1016/j.chom.2021.04.004
105. Zhang H, DiBaise JK, Zuccolo A, et al. Human gut microbiota in obesity and after gastric bypass. Proceedings of the National Academy of Sciences. 2009;106(7):2365-2370. doi: https://doi.org/10.1073/pnas.0812600106
106. Aron-Wisnewsky J, Prifti E, Belda E, et al. Major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut. 2019;68(1):70. doi: https://doi.org/10.1136/gutjnl-2018-316103
107. West KA, Kanu C, Maric T, et al. Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery. Gut. 2020;69(8):1452-1459. doi: https://doi.org/10.1136/gutjnl-2019-319620
108. Davies N, O’Sullivan JM, Plank LD, et al. Gut Microbial Predictors of Type 2 Diabetes Remission Following Bariatric Surgery. Obes Surg. 2020;30(9):3536-3548. doi: https://doi.org/10.1007/s11695-020-04684-0
109. Mabey JG, Chaston JM, Castro DG, et al. Gut microbiota differs a decade after bariatric surgery relative to a nonsurgical comparison group. Surg Obes Relat Dis. 2020;16(9):1304-1311. doi: https://doi.org/10.1016/j.soard.2020.04.006
110. Ilhan ZE, DiBaise JK, Dautel SE, et al. Temporospatial shifts in the human gut microbiome and metabolome after gastric bypass surgery. npj Biofilms Microbiomes. 2020;6(1):12. doi: https://doi.org/10.1038/s41522-020-0122-5
111. Palaiodimos L, Kokkinidis DG, Li W, et al. Severe obesity, increasing age and male sex are independently associated with worse inhospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York. Metabolism. 2020;108:154262. doi: https://doi.org/10.1016/j.metabol.2020.154262
112. Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966. doi: https://doi.org/10.1136/bmj.m1966
113. Kalligeros M, Shehadeh F, Mylona EK, et al. Association of Obesity with Disease Severity Among Patients with Coronavirus Disease 2019. Obesity (Silver Spring). 2020;28(7):1200-1204. doi: https://doi.org/10.1002/oby.22859
114. Simonnet A, Chetboun M, Poissy J, et al. High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation. Obesity (Silver Spring). 2020;28(7):1195-1199. doi: https://doi.org/10.1002/oby.22831
115. Hur K, Price CPE, Gray EL, et al. Factors Associated With Intubation and Prolonged Intubation in Hospitalized Patients With COVID-19. Otolaryngol Head Neck Surg. 2020;163(1):170-178. doi: https://doi.org/10.1177/0194599820929640
116. Tartof SY, Qian L, Hong V, et al. Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization. Ann Intern Med. 2020;173(10):773-781. doi: https://doi.org/10.7326/M20-3742
117. Ko JY, Danielson ML, Town M, et al. Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization: COVID-19–Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System. Clin Infect Dis. 2021;72(11):e695-e703. doi: https://doi.org/10.1093/cid/ciaa1419
118. Zhu Z, Hasegawa K, Ma B, Fujiogi M, Camargo CA, Liang L. Association of obesity and its genetic predisposition with the risk of severe COVID-19: Analysis of population-based cohort data. Metabolism. 2020;112:154345. doi: https://doi.org/10.1016/j.metabol.2020.154345
119. Ellinghaus D, Degenhardt F, Bujanda L, et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med. 2020;383(16):1522-1534. doi: https://doi.org/10.1056/NEJMoa2020283
120. Shelton JF, Shastri AJ, Ye C, et al. Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity. Nature Genetics. 2021;53(6):801-808. doi: https://doi.org/10.1038/s41588-021-00854-7
121. Pulit SL, Stoneman C, Morris AP, et al. Meta-analysis of genomewide association studies for body fat distribution in 694 649 individuals of European ancestry. Hum Mol Genet. 2019;28(1):166-174. doi: https://doi.org/10.1093/hmg/ddy327
122. Dubé M-P, Lemaçon A, Barhdadi A, et al. Genetics of symptom remission in outpatients with COVID-19. Scientific Reports. 2021;11(1):10847. doi: https://doi.org/10.1038/s41598-021-90365-6
123. Roos J, Dahlhaus M, Funcke J-B, et al. miR-146a regulates insulin sensitivity via NPR3. Cellular and Molecular Life Sciences. 2021;78(6):2987-3003. doi: https://doi.org/10.1007/s00018-020-03699-1
124. Aung N, Khanji MY, Munroe PB, Petersen SE. Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study. Front Genet. 2020;11. doi: https://doi.org/10.3389/fgene.2020.586308
125. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273. doi: https://doi.org/10.1038/s41586-020-2012-7
126. Al-Benna S. Association of high level gene expression of ACE2 in adipose tissue with mortality of COVID-19 infection in obese patients. Obes Med. 2020;19:100283. doi: https://doi.org/10.1016/j.obmed.2020.100283
127. Pinheiro T de A, Barcala-Jorge AS, Andrade JMO, et al. Obesity and malnutrition similarly alter the renin–angiotensin system and inflammation in mice and human adipose. J Nutr Biochem. 2017;48(11):74-82. doi: https://doi.org/10.1016/j.jnutbio.2017.06.008
128. Radzikowska U, Ding M, Tan G, et al. Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors. Allergy. 2020;75(11):2829-2845. doi: https://doi.org/10.1111/all.14429
129. Sell H, Bluher M, Kloting N, et al. Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro. Diabetes Care. 2013;36(12):4083-4090. doi: https://doi.org/10.2337/dc13-0496
130. Bassendine MF, Bridge SH, McCaughan GW, Gorrell MD. COVID-19 and comorbidities: A role for dipeptidyl peptidase 4 in disease severity? J Diabetes. 2020;12(9):649-658. doi: https://doi.org/10.1111/1753-0407.13052
131. Ritter A, Kreis NN, Louwen F, et al. Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics. Int J Mol Sci. 2020;21(16):5793. doi: https://doi.org/10.3390/ijms21165793
132. Yanagimachi T, Fujita Y, Takeda Y, et al. Dipeptidyl peptidase-4 inhibitor treatment induces a greater increase in plasma levels of bioactive GIP than GLP-1 in nondiabetic subjects. Molecular Metabolism. 2017;62:226-231. doi: https://doi.org/10.1016/j.molmet.2016.12.009
133. Marques AP, Cunha-Santos J, Leal H, et al. Dipeptidyl peptidase IV (DPP-IV) inhibition prevents fibrosis in adipose tissue of obese mice. Biochim Biophys Acta Gen Subj. 2018;1862(3):403-413. doi: https://doi.org/10.1016/j.bbagen.2017.11.012
134. Rohrborn D, Eckel J, Sell H. Shedding of dipeptidyl peptidase 4 is mediated by metalloproteases and upregulated by hypoxia in human adipocytes and smooth muscle cells. Febs Letters. 2014;588(21):3870-3877. doi: https://doi.org/10.1016/j.febslet.2014.08.029
135. Gallwitz B. Clinical Use of DPP-4 Inhibitors. Front Endocrinol (Lausanne). 2019;10. doi: https://doi.org/10.3389/fendo.2019.00389
136. Song J, Li Y, Huang X, et al. Systematic analysis of ACE2 and TMPRSS2 expression in salivary glands reveals underlying transmission mechanism caused by SARS-CoV-2. J Med Virol. 2020;92(11):2556-2566. doi: https://doi.org/10.1002/jmv.26045
137. Shin K, Pandey A, Liu XQ, et al. Preferential apelin-13 production by the proprotein convertase PCSK3 is implicated in obesity. Febs Open Bio. 2013;3:328-333. doi: https://doi.org/10.1016/j.fob.2013.08.001
138. Cyranoski D. Profile of a killer: the complex biology powering the coronavirus pandemic. Nature. 2020;581(7806):22-26. doi: https://doi.org/10.1038/d41586-020-01315-7
139. Cinti S, Mitchell G, Barbatelli G, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46(11):2347-2355. doi: https://doi.org/10.1194/jlr.M500294-JLR200
140. Marques-Vidal P, Bastardot F, von Känel R, et al. Association between circulating cytokine levels, diabetes and insulin resistance in a population-based sample (CoLaus study). Clin Endocrinol (Oxf ). 2013;78(2):232-241.doi: https://doi.org/10.1111/j.1365-2265.2012.04384.x
141. Lockhart SM, O’Rahilly S. When Two Pandemics Meet: Why Is Obesity Associated with Increased COVID-19 Mortality? Med. 2020;1(1):33-42. doi: https://doi.org/10.1016/j.medj.2020.06.005
142. Kreutz R, Algharably EAE-H, Azizi M, et al. Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19. Cardiovasc Res. 2020;116(10):1688-1699. doi: https://doi.org/10.1093/cvr/cvaa097
143. Louwen F, Ritter A, Kreis N, et al. Insight into the development of obesity: functional alterations of adipose-derived mesenchymal stem cells. Obesity Reviews. 2018;19(7):888-904. doi: https://doi.org/10.1111/obr.12679
144. Ritter A, Louwen F, Yuan J, Deficient primary cilia in obese adipose-derived mesenchymal stem cells: obesity, a secondary ciliopathy? Obes Rev. 2018;19(10):1317-1328. doi: https://doi.org/10.1111/obr.12716
145. Ritter A, Kreis NN, Roth S, et al. Restoration of primary cilia in obese adipose-derived mesenchymal stem cells by inhibiting Aurora A or extracellular signal-regulated kinase. Stem Cell Res Ther. 2019;10(1)255. doi: https://doi.org/10.1186/s13287-019-1373-z
146. Onate B, Vilahur G, Camino-Lopez S, et al. Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype. BMC Genomics. 2013;14(1):625. doi: https://doi.org/10.1186/1471-2164-14-625
147. Gealekman O, Guseva N, Hartigan C, et al. Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity. Circulation. 2011;123(2):186-194. doi: https://doi.org/10.1161/CIRCULATIONAHA.110.970145
148. Oñate B, Vilahur G, Ferrer-Lorente R, et al. The subcutaneous adipose tissue reservoir of functionally active stem cells is reduced in obese patients. FASEB J. 2012;26(10):4327-4336. doi: https://doi.org/10.1096/fj.12-207217
149. Serena C, Keiran N, Ceperuelo-Mallafre V, et al. Obesity and Type 2 Diabetes Alters the Immune Properties of Human Adipose Derived Stem Cells. Stem Cells. 2016;34(10):2559-2573. doi: https://doi.org/10.1002/stem.2429
150. Oliva-Olivera W, Gea AL, Lhamyani S, et al. Differences in the Osteogenic Differentiation Capacity of Omental Adipose-Derived Stem Cells in Obese Patients With and Without Metabolic Syndrome. Endocrinology. 2015;156(12):4492-4501. doi: https://doi.org/10.1210/en.2015-1413
151. Mariani S, Di Rocco G, Toietta G, et al. Sirtuins 1–7 expression in human adipose-derived stem cells from subcutaneous and visceral fat depots: influence of obesity and hypoxia. Endocrine. 2017;57(3):455-463. doi: https://doi.org/10.1007/s12020-016-1170-8
152. Ritter A, Friemel A, Kreis NN, et al. Primary Cilia Are Dysfunctional in Obese Adipose-Derived Mesenchymal Stem Cells. Stem Cell Reports. 2018;10(2):583-599. doi: https://doi.org/10.1016/j.stemcr.2017.12.022
153. Xie T, Liang J, Liu N, et al. Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis. The Journal of clinical investigation. 2016;126(8):3063-3079. doi: https://doi.org/10.1172/JCI85328
154. Kramann R, Schneider RK, DiRocco DP, et al. Perivascular Gli1+ Progenitors Are Key Contributors to Injury-Induced Organ Fibrosis. Cell Stem Cell. 2015;16(1):51-66. doi: https://doi.org/10.1016/j.stem.2014.11.004
155. Marriott S, Baskir RS, Gaskill C, et al. ABCG2 pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling. Am J Physiol Physiol. 2014;307(8):C684-C698. doi: https://doi.org/10.1152/ajpcell.00114.2014
156. Chuang H-M, Shih TE, Lu K-Y, et al. Mesenchymal Stem Cell Therapy of Pulmonary Fibrosis. Cell Transplant. 2018;27(11):1581-1587. doi: https://doi.org/10.1177/0963689718787501
157. Simones AA, Beisang DJ, Panoskaltsis-Mortari A, Roberts KD. Mesenchymal stem cells in the pathogenesis and treatment of bronchopulmonary dysplasia: a clinical review. Pediatr Res. 2018;83(1-2):308-317. doi: https://doi.org/10.1038/pr.2017.237
158. Bhattacharya D., Dwivedi V. Understanding the Role of Mesenchymal Stem Cells in Infectious Diseases: Focus on Tuberculosis, Malaria. Sepsis and HIV. Electronic J Biol 2016;12(3).
159. Waldner M, Zhang W, James IB, et al. Characteristics and Immunomodulating Functions of Adipose-Derived and Bone Marrow-Derived Mesenchymal Stem Cells Across Defined Human Leukocyte Antigen Barriers. Front Immunol. 2018;9:1642. doi: https://doi.org/10.3389/fimmu.2018.01642
160. Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Front Immunol. 2019;10:1191. doi: https://doi.org/10.3389/fimmu.2019.01191
Supplementary files
|
1. Figure 1. Genetic structure of obesity. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(286KB)
|
Indexing metadata ▾ |
|
2. Figure 2. Metabolic consequences of altering the gut microbiome | |
Subject | ||
Type | Исследовательские инструменты | |
View
(335KB)
|
Indexing metadata ▾ |
Review
For citations:
Timasheva Ya.R., Balkhiyarova Zh.R., Kochetova O.V. Current state of the obesity research: genetic aspects, the role of microbiome, and susceptibility to COVID-19. Problems of Endocrinology. 2021;67(4):20-35. (In Russ.) https://doi.org/10.14341/probl12775

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).