cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2022-3109cardiovascular-3109Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEW ARTICLESЭпидемия ожирения через призму эволюционных процессовObesity epidemic through the prism of evolutionary processeshttps://orcid.org/0000-0002-0332-7696КимО. Т.KimO. T.

Ольга Трофимовна Ким — младший научный сотрудник отдела фундаментальных и прикладных аспектов ожирения.

Москва. Тел.: +7 (901) 507-49-87

Moscow

olgakimt06@gmail.comhttps://orcid.org/0000-0002-4453-8430ДрапкинаО. М.DrapkinaO. M.

Доктор медицинских наук, профессор, член-корр. РАН, директор.

Москва

Moscow

ФГБУ Национальный медицинский исследовательский центр терапии и профилактической медицины Минздрава РоссииNational Medical Research Center for Therapy and Preventive Medicine20222801202221131093109Copyright © Ким О.Т., Драпкина О.М., 20222022Ким О.Т., Драпкина О.М.Kim O.T., Drapkina O.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/3109

В настоящее время ожирение стало одной из самых серьезных проблем общественного здоровья. Оно ежегодно уносит миллионы жизней во всем мире из-за его связи со многочисленными ассоциированными заболеваниями и приводит к значительным социальным и экономическим потерям. Общепризнано, что ожирение является результатом взаимодействия генов и окружающей среды, и предрасположенность к нему лежит в нашем эволюционном прошлом. В настоящем обзоре обсуждается роль жировой ткани в процессе эволюции человека, факторы, определяющие склонность человека к ожирению, основные гипотезы происхождения ожирения и вытекающие из них потенциальные стратегии профилактики и лечения. Также рассматриваются эволюционное значение висцеральной жировой ткани и некоторые этнические и гендерные особенности, связанные с ее распределением.

Currently, obesity has become one of the most serious public health problems. It takes millions of lives worldwide every year due to its association with numerous diseases and leads to significant social and economic losses. It is generally accepted that obesity is the result of the interaction of genes and environment, and the predisposition to it lies in our evolutionary past. This review discusses the role of adipose tissue in human evolution, the factors specifying a person’s predisposition to obesity, the main hypotheses for obesity origin, and potential prevention and treatment strategies arising from them. The evolutionary significance of visceral adipose tissue and some ethnic and sex characteristics associated with its distribution are also considered.

ожирениеожирение/эволюционная теориягипотеза экономного генотипагипотеза экономного фенотипагипотеза экономного эпигеномагипотеза дрейфа геновгипотеза страхованиявисцеральное ожирениеobesityobesity/evolutionary theorythrifty gene hypothesisthrifty phenotype hypothesisthrifty epigenome hypothesisdrifty gene hypothesisinsurance hypothesisvisceral obesityАвторы выражают благодарность академику РАН Намазовой-Барановой Л. С. за ценные советы и замечания, высказанные в процессе написания статьиThe authors are grateful to Academician of RAS Namazova-Baranova L. S. for valuable advices and comments during the writing of this articleReferencesWHO. Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight_(29.10.2021).WHO. Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight_(29.10.2021).Bodirsky BL, Dietrich JP, Martinelli E, et al. The ongoing nutrition transition thwarts long-term targets for food security, public health and environmental protection. Sci Rep. 2020;10(1):19778. doi:10.1038/s41598-020-75213-3.Bodirsky BL, Dietrich JP, Martinelli E, et al. The ongoing nutrition transition thwarts long-term targets for food security, public health and environmental protection. Sci Rep. 2020;10(1):19778. doi:10.1038/s41598-020-75213-3.GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223-49. doi:10.1016/S0140-6736(20)30752-2.GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223-49. doi:10.1016/S0140-6736(20)30752-2.Wells JC. The evolution of human adiposity and obesity: where did it all go wrong? Dis Model Mech. 2012;5(5):595-607. doi:10.1242/dmm.009613.Wells JC. The evolution of human adiposity and obesity: where did it all go wrong? Dis Model Mech. 2012;5(5):595-607. doi:10.1242/dmm.009613.Nesse RM, Bergstrom CT, Ellison PT, et al. Evolution in health and medicine Sackler colloquium: Making evolutionary biology a basic science for medicine. Proc Natl Acad Sci U S A. 2010;107(Suppl 1):1800-7. doi:10.1073/pnas.0906224106.Nesse RM, Bergstrom CT, Ellison PT, et al. Evolution in health and medicine Sackler colloquium: Making evolutionary biology a basic science for medicine. Proc Natl Acad Sci U S A. 2010;107(Suppl 1):1800-7. doi:10.1073/pnas.0906224106.Piaggi P, Vinales KL, Basolo A, et al. Energy expenditure 12. in the etiology of human obesity: spendthrift and thrifty metabolic phenotypes and energy-sensing mechanisms. J Endocrinol Invest. 2018;41(1):83-9. doi:10.1007/s40618-13.017-0732-9.Piaggi P, Vinales KL, Basolo A, et al. Energy expenditure 12. in the etiology of human obesity: spendthrift and thrifty metabolic phenotypes and energy-sensing mechanisms. J Endocrinol Invest. 2018;41(1):83-9. doi:10.1007/s40618-13.017-0732-9.Birsoy K, Festuccia WT, Laplante M. A comparative perspective on lipid storage in animals. J Cell Sci. 2013;126(Pt 7):1541-52. doi:10.1242/jcs.104992.Birsoy K, Festuccia WT, Laplante M. A comparative perspective on lipid storage in animals. J Cell Sci. 2013;126(Pt 7):1541-52. doi:10.1242/jcs.104992.O’rourke RW. Metabolic thrift and the genetic basis of human obesity. Ann Surg. 2014;259(4):642-8. doi: 10.1097/SLA.0000000000000361.O’rourke RW. Metabolic thrift and the genetic basis of human obesity. Ann Surg. 2014;259(4):642-8. doi: 10.1097/SLA.0000000000000361.Butte NF, Hopkinson JM, Wong WW, et al. Body composition during the first 2 years of life: an updated reference. Pediatr Res. 2000;47(5):578-85. doi:10.1203/00006450-200005000-00004.Butte NF, Hopkinson JM, Wong WW, et al. Body composition during the first 2 years of life: an updated reference. Pediatr Res. 2000;47(5):578-85. doi:10.1203/00006450-200005000-00004.Jensen NJ, Wodschow HZ, Nilsson M, et al. Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases. Int J Mol Sci. 2020;21(22):8767. doi:10.3390/ijms21228767.Jensen NJ, Wodschow HZ, Nilsson M, et al. Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases. Int J Mol Sci. 2020;21(22):8767. doi:10.3390/ijms21228767.Fontana R, Della Torre S. The Deep Correlation between Energy Metabolism and Reproduction: A View on the Effects of Nutrition for Women Fertility. Nutrients. 2016;8(2):87. doi:10.3390/nu8020087.Fontana R, Della Torre S. The Deep Correlation between Energy Metabolism and Reproduction: A View on the Effects of Nutrition for Women Fertility. Nutrients. 2016;8(2):87. doi:10.3390/nu8020087.Straub RH. Evolutionary medicine and chronic inflammatory state-known and new concepts in pathophysiology. J Mol Med (Berl). 2012;90(5):523-34. doi:10.1007/s00109-012-0861-8.Straub RH. Evolutionary medicine and chronic inflammatory state-known and new concepts in pathophysiology. J Mol Med (Berl). 2012;90(5):523-34. doi:10.1007/s00109-012-0861-8.Manna M, Nieminen T, Vattulainen I. Understanding the Role of Lipids in Signaling Through Atomistic and Multiscale Simulations of Cell Membranes. Annu Rev Biophys. 2019;48:421-39. doi:10.1146/annurev-biophys-052118-115553.Manna M, Nieminen T, Vattulainen I. Understanding the Role of Lipids in Signaling Through Atomistic and Multiscale Simulations of Cell Membranes. Annu Rev Biophys. 2019;48:421-39. doi:10.1146/annurev-biophys-052118-115553.Huang-Doran I, Sleigh A, Rochford JJ, et al. Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol. 2010;207(3):245-55. doi:10.1677/JOE-10-0272.Huang-Doran I, Sleigh A, Rochford JJ, et al. Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol. 2010;207(3):245-55. doi:10.1677/JOE-10-0272.Zwick RK, Guerrero-Juarez CF, Horsley V, et al. Anatomical, Physiological, and Functional Diversity of Adipose Tissue. Cell Metab. 2018;27(1):68-83. doi:10.1016/j.cmet.2017.12.002.Zwick RK, Guerrero-Juarez CF, Horsley V, et al. Anatomical, Physiological, and Functional Diversity of Adipose Tissue. Cell Metab. 2018;27(1):68-83. doi:10.1016/j.cmet.2017.12.002.Higginson AD, McNamara JM, Houston AI. Fatness and fitness: exposing the logic of evolutionary explanations for obesity. Proc Biol Sci. 2016;283(1822):20152443. doi:10.1098/rspb.2015.2443.Higginson AD, McNamara JM, Houston AI. Fatness and fitness: exposing the logic of evolutionary explanations for obesity. Proc Biol Sci. 2016;283(1822):20152443. doi:10.1098/rspb.2015.2443.Genne-Bacon EA. Thinking evolutionarily about obesity. Yale J Biol Med. 2014;87(2):99-112.Genne-Bacon EA. Thinking evolutionarily about obesity. Yale J Biol Med. 2014;87(2):99-112.Coccurello R, Maccarrone M. Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back. Front Neurosci. 2018;12:271. doi:10.3389/fnins.2018.00271.Coccurello R, Maccarrone M. Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back. Front Neurosci. 2018;12:271. doi:10.3389/fnins.2018.00271.Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet. 1962;14(4):353-62.Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet. 1962;14(4):353-62.Goodarzi MO. Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes Endocrinol. 2018;6(3):223-36. doi:10.1016/S2213-8587(17)30200-0.Goodarzi MO. Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes Endocrinol. 2018;6(3):223-36. doi:10.1016/S2213-8587(17)30200-0.Pontzer H, Wood BM, Raichlen DA. Hunter-gatherers as models in public health. Obes Rev. 2018;19(Suppl 1):24-35. doi:10.1111/obr.12785.Pontzer H, Wood BM, Raichlen DA. Hunter-gatherers as models in public health. Obes Rev. 2018;19(Suppl 1):24-35. doi:10.1111/obr.12785.NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 1289 million children, adolescents, and adults. Lancet. 2017;390(10113):2627-42. doi:10.1016/S0140-6736(17)32129-3.NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 1289 million children, adolescents, and adults. Lancet. 2017;390(10113):2627-42. doi:10.1016/S0140-6736(17)32129-3.Baschetti R. Diabetes epidemic in newly westernized populations: is it due to thrifty genes or to genetically unknown foods? J R Soc Med. 1998;91(12):622-5. doi: 10.1177/014107689809101203.Baschetti R. Diabetes epidemic in newly westernized populations: is it due to thrifty genes or to genetically unknown foods? J R Soc Med. 1998;91(12):622-5. doi: 10.1177/014107689809101203.Dombrowski SU, Knittle K, Avenell A, et al. Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials. BMJ. 2014;348:g2646. doi:10.1136/bmj.g2646.Dombrowski SU, Knittle K, Avenell A, et al. Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials. BMJ. 2014;348:g2646. doi:10.1136/bmj.g2646.Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35(7):595-601. doi:10.1007/BF00400248.Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35(7):595-601. doi:10.1007/BF00400248.Shaheen R, Persson LA, Ahmed S, et al. Cost-effectiveness of invitation to food supplementation early in pregnancy combined with multiple micronutrients on infant survival: analysis of data from MINIMat randomized trial, Bangladesh. BMC Pregnancy Childbirth. 2015;15:125. doi:10.1186/s12884-015-0551-y.Shaheen R, Persson LA, Ahmed S, et al. Cost-effectiveness of invitation to food supplementation early in pregnancy combined with multiple micronutrients on infant survival: analysis of data from MINIMat randomized trial, Bangladesh. BMC Pregnancy Childbirth. 2015;15:125. doi:10.1186/s12884-015-0551-y.Garmendia ML, Corvalan C, Araya M, et al. Effectiveness of a normative nutrition intervention in Chilean pregnant women on maternal and neonatal outcomes: the CHiMINCs study. Am J Clin Nutr. 2020;112(4):991-1001. doi:10.1093/ajcn/nqaa185.Garmendia ML, Corvalan C, Araya M, et al. Effectiveness of a normative nutrition intervention in Chilean pregnant women on maternal and neonatal outcomes: the CHiMINCs study. Am J Clin Nutr. 2020;112(4):991-1001. doi:10.1093/ajcn/nqaa185.Stoger R. The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes? Bioessays. 2008;30(2): 156-66. doi:10.1002/bies.20700.Stoger R. The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes? Bioessays. 2008;30(2): 156-66. doi:10.1002/bies.20700.Jaacks LM, Vandevijvere S, Pan A, et al. The obesity transition: stages of the global epidemic. Lancet Diabetes Endocrinol. 2019;7(3):231-40. doi:10.1016/S2213-8587(19)30026-9.Jaacks LM, Vandevijvere S, Pan A, et al. The obesity transition: stages of the global epidemic. Lancet Diabetes Endocrinol. 2019;7(3):231-40. doi:10.1016/S2213-8587(19)30026-9.Speakman JR. Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the ‘drifty gene’ hypothesis. Int J Obes (Lond). 2008;32(11):1611-7 doi:10.1038/ijo.2008.161.Speakman JR. Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the ‘drifty gene’ hypothesis. Int J Obes (Lond). 2008;32(11):1611-7 doi:10.1038/ijo.2008.161.Prentice AM, Hennig BJ, Fulford AJ. Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release? Int J Obes (Lond). 2008;32(11):1607-10. doi:10.1038/ijo.2008.147.Prentice AM, Hennig BJ, Fulford AJ. Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release? Int J Obes (Lond). 2008;32(11):1607-10. doi:10.1038/ijo.2008.147.Wells JC. The evolution of human fatness and susceptibility to obesity: an ethological approach. Biol Rev Camb Philos Soc. 2006;81(2):183-205. doi:10.1017/S1464793105006974.Wells JC. The evolution of human fatness and susceptibility to obesity: an ethological approach. Biol Rev Camb Philos Soc. 2006;81(2):183-205. doi:10.1017/S1464793105006974.Elliston KG, Ferguson SG, Schuz N, et al. Situational cues and momentary food environment predict everyday eating behavior in adults with overweight and obesity. Health Psychol. 2017;36(4):337-45. doi:10.1037/hea0000439.Elliston KG, Ferguson SG, Schuz N, et al. Situational cues and momentary food environment predict everyday eating behavior in adults with overweight and obesity. Health Psychol. 2017;36(4):337-45. doi:10.1037/hea0000439.Global Obesity Observatory. https://data.worldobesity.org/. (29.10.2021) .Global Obesity Observatory. https://data.worldobesity.org/. (29.10.2021) .Nettle D, Andrews C, Bateson M. Food insecurity as a driver of obesity in humans: The insurance hypothesis. Behav Brain Sci. 2017;40:e105. doi:10.1017/S0140525X16000947Nettle D, Andrews C, Bateson M. Food insecurity as a driver of obesity in humans: The insurance hypothesis. Behav Brain Sci. 2017;40:e105. doi:10.1017/S0140525X16000947Rogers CM. Testing optimal body mass theory: Evidence for cost of fat in wintering birds. Ecosphere. 2015;6:1-12.Rogers CM. Testing optimal body mass theory: Evidence for cost of fat in wintering birds. Ecosphere. 2015;6:1-12.Mark S. Witter, John P. Swaddle, Dominance, competition, and energetic reserves in the European starling, Sturnus vulgaris. Behavioral Ecology1995;6(Issue 3):343-8. doi:10.1093/beheco/6.3.343.Mark S. Witter, John P. Swaddle, Dominance, competition, and energetic reserves in the European starling, Sturnus vulgaris. Behavioral Ecology1995;6(Issue 3):343-8. doi:10.1093/beheco/6.3.343.Ross R, Neeland IJ, Yamashita S, et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020;16(3):177-89. doi:10.1038/s41574-019-0310-7.Ross R, Neeland IJ, Yamashita S, et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020;16(3):177-89. doi:10.1038/s41574-019-0310-7.Wang AW, Prieto JM, Cauvi DM, et al. The Greater Omentum-A Vibrant and Enigmatic Immunologic Organ Involved in Injury and Infection Resolution. Shock. 2020;53(4):384-90. doi: 10.1097/SHK.0000000000001428.Wang AW, Prieto JM, Cauvi DM, et al. The Greater Omentum-A Vibrant and Enigmatic Immunologic Organ Involved in Injury and Infection Resolution. Shock. 2020;53(4):384-90. doi: 10.1097/SHK.0000000000001428.Meza-Perez S, Randall TD. Immunological Functions of the Omentum. Trends Immunol. 2017;38(7):526-36. doi: 10.1016/j.it.201703.002.Meza-Perez S, Randall TD. Immunological Functions of the Omentum. Trends Immunol. 2017;38(7):526-36. doi: 10.1016/j.it.201703.002.Khan S, Luck H, Winer S, et al. Emerging concepts in intestinal immune control of obesity-related metabolic disease. Nat Commun. 2021; 12(1 ):2598. doi:10.1038/s41467-021-22727-7Khan S, Luck H, Winer S, et al. Emerging concepts in intestinal immune control of obesity-related metabolic disease. Nat Commun. 2021; 12(1 ):2598. doi:10.1038/s41467-021-22727-7West-Eberhard MJ. Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity. Proc Natl Acad Sci USA. 2019;116(3):723-31. doi:10.1073/pnas.1809046116.West-Eberhard MJ. Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity. Proc Natl Acad Sci USA. 2019;116(3):723-31. doi:10.1073/pnas.1809046116.Suarez-Cuenca JA, De La Pena-Sosa G, De La Vega-Moreno K, et al. Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity. Sci Rep. 2021;11(1):1831. doi:10.1038/s41598-021-81289-2.Suarez-Cuenca JA, De La Pena-Sosa G, De La Vega-Moreno K, et al. Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity. Sci Rep. 2021;11(1):1831. doi:10.1038/s41598-021-81289-2.Garcfa-Ruiz I, Solfs-Munoz P, Fernandez-Moreira D, et al. Omentectomy Prevents Metabolic Syndrome By Reducing Appetite and Body Weight In A Diet-Induced Obesity Rat Model. Sci Rep. 2018;8( 1): 1540. doi:10.1038/s41598-018-19973-z.Garcfa-Ruiz I, Solfs-Munoz P, Fernandez-Moreira D, et al. Omentectomy Prevents Metabolic Syndrome By Reducing Appetite and Body Weight In A Diet-Induced Obesity Rat Model. Sci Rep. 2018;8( 1): 1540. doi:10.1038/s41598-018-19973-z.Williams R, Periasamy M. Genetic and Environmental Factors Contributing to Visceral Adiposity in Asian Populations. Endocrinol Metab (Seoul). 2020;35(4):681-95. doi:10.3803/EnM.2020.772.Williams R, Periasamy M. Genetic and Environmental Factors Contributing to Visceral Adiposity in Asian Populations. Endocrinol Metab (Seoul). 2020;35(4):681-95. doi:10.3803/EnM.2020.772.Palaniappan LP, Wong EC, Shin JJ, Fortmann SP, Lauderdale DS. Asian Americans have greater prevalence of metabolic syndrome despite lower body mass index. Int J Obes (Lond). 2011;35(3):393-400. doi:10.1038/ijo.2010.152.Palaniappan LP, Wong EC, Shin JJ, Fortmann SP, Lauderdale DS. Asian Americans have greater prevalence of metabolic syndrome despite lower body mass index. Int J Obes (Lond). 2011;35(3):393-400. doi:10.1038/ijo.2010.152.Contreras RE, Schriever SC, Pfluger PT. Physiological and Epigenetic Features of Yoyo Dieting and Weight Control. Front Genet. 2019;10:1015. doi:10.3389/fgene.2019.01015.Contreras RE, Schriever SC, Pfluger PT. Physiological and Epigenetic Features of Yoyo Dieting and Weight Control. Front Genet. 2019;10:1015. doi:10.3389/fgene.2019.01015.Corrales P, Vidal-Puig A, Medina-Gomez G. Obesity and pregnancy, the perfect metabolic storm. Eur J Clin Nutr. 2021;75(12):1723-34. doi:10.1038/s41430-021-00914-5.Corrales P, Vidal-Puig A, Medina-Gomez G. Obesity and pregnancy, the perfect metabolic storm. Eur J Clin Nutr. 2021;75(12):1723-34. doi:10.1038/s41430-021-00914-5.WHO. Social determinants of health. https://www.who.int/health-topics/social-determinants-of-health#tab=tab_1. (29.10.2021).WHO. Social determinants of health. https://www.who.int/health-topics/social-determinants-of-health#tab=tab_1. (29.10.2021).

The authors declare that there are no conflicts of interest present.