Many internal and external factors are related to obesity. Pathogens that can induce obesity are the most interesting external factors. While the relationship between pathogenic human intestinal microbiota and obesity has been extensively studied, viruses have received relatively little attention. Among the human obesity-related viruses, adenovirus 36 (Ad36) is most commonly associated with obesity.
A literature search was conducted using the articles in the PubMed database published from April 1982 to April 2019. The following main keywords were used: (‘adenovirus 36’) and (‘obesity’) and (‘cellular mechanism’ or ‘genetic factor’ or ‘immune response’ or ‘inflammation’).
In this review, we have discussed the known facts and what requires to be understood regarding Ad36-induced obesity. In particular, we have summarized the cellular mechanism of Ad36-induced obesity, as well as the genetic and immunological factors affected by Ad36 infection. Ad36 infection increases adipogenesis in animals and humans. Ad36-induced inflammation contributes to angiogenesis in adipose tissues, thereby maintaining proper glycemic control and metabolic robustness. The E4orf1 protein derived from Ad36 is responsible for increasing glucose uptake due to the translocation of GLUT4 via the Ras-PI3K pathway, which is involved in ‘distal’ insulin signaling.
We expect that this review will assist in guiding future investigations regarding Ad36-induced obesity. (1) Identification of the direct and indirect factors affecting Ad36-induced obesity and understanding their mechanism of action and (2) utilization of the Ad36-induced improvement in glycemic control for clinical applications, with efforts toward developing E4orf1-based drugs.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Obesity Surgery Open Access 22 January 2021
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Lyons MJ, Faust IM, Hemmes RB, Buskirk DR, Hirsch J, Zabriskie JB. A virally induced obesity syndrome in mice. Science. 1982;216:82–5.
Dhurandhar NV, Kulkarni P, Ajinkya SM, Sherikar A. Effect of adenovirus infection on adiposity in chicken. Vet Microbiol. 1992;31:101–7.
Whigham LD, Israel BA, Atkinson RL. Adipogenic potential of multiple human adenoviruses in vivo and in vitro in animals. Am J Physiol Regul Integr Comp Physiol. 2006;290:R190–4.
Akheruzzaman M, Hegde V, Dhurandhar NV. Twenty-five years of research about adipogenic adenoviruses: a systematic review. Obes Rev. 2019;20:499–509.
Dhurandhar NV, Israel BA, Kolesar JM, Mayhew G, Cook ME, Atkinson RL. Transmissibility of adenovirus-induced adiposity in a chicken model. Int J Obes (Lond). 2001;25:990–6.
Montes-Galindo DA, Espiritu-Mojarro AC, Melnikov V, Moy-López NA, Soriano-Hernandez AD, Galvan-Salazar HR, et al. Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high-fat diet: a study on hamsters. Arch Virol. 2019;164:775–86.
Dhurandhar NV, Whigham LD, Abbott DH, Schultz-Darken NJ, Israel BA, Bradley SM, et al. Human adenovirus Ad-36 promotes weight gain in male rhesus and marmoset monkeys. J Nutr. 2002;132:3155–60.
Pasarica M, Loiler S, Dhurandhar NV. Acute effect of infection by adipogenic human adenovirus Ad36. Arch Virol. 2008;153:2097–102.
Na HN, Hong YM, Michael BY, Park SH, Kim IB, Nam JH. Adenovirus 36 attenuates weight loss from exercise but improves glycemic control by increasing mitochondrial activity in the liver. PLoS One. 2014;9:e114534.
Shang Q, Wang H, Song Y, Wei L, Lavebratt C, Zhang F, et al. Serological data analyses show that adenovirus 36 infection is associated with obesity: a meta-analysis involving 5739 subjects. Obesity (Silver Spring). 2014;22:895–900.
Xu MY, Cao B, Wang DF, Guo JH, Chen KL, Shi M, et al. Human adenovirus 36 infection increased the risk of obesity: a meta-analysis update. Medicine. 2015;94:e2357.
Yamada T, Hara K, Kadowaki T. Association of adenovirus 36 infection with obesity and metabolic markers in humans: a meta-analysis of observational studies. PLoS One. 2012;7:e42031.
Atkinson RL, Dhurandhar NV, Allison DB, Bowen RL, Israel BA, Albu JB, et al. Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int J Obes (Lond). 2005;29:281–6.
Atkinson RL, Lee I, Shin HJ, He J. Human adenovirus-36 antibody status is associated with obesity in children. Int J Pediatr Obes. 2010;5:157–60.
Broderick M, Hansen C, Irvine M, Metzgar D, Campbell K, Baker C, et al. Adenovirus 36 seropositivity is strongly associated with race and gender, but not obesity, among US military personnel. Int J Obes (Lond). 2010;34:302–8.
Gabbert C, Donohue M, Arnold J, Schwimmer JB. Adenovirus 36 and obesity in children and adolescents. Pediatrics. 2010;126:721–6.
Goossens VJ, de Jager SA, Grauls GE, Gielen M, Vlietinck RF, Derom CA, et al. Lack of evidence for the role of human adenovirus‐36 in obesity in a European cohort. Obesity. 2011;19:220–1.
Na HN, Hong YM, Kim J, Kim HK, Jo I, Nam JH. Association between human adenovirus-36 and lipid disorders in Korean schoolchildren. Int J Obes (Lond). 2010;34:89–93.
Na HN, Kim J, Lee HS, Shim KW, Kimm H, Jee SH, et al. Association of human adenovirus-36 in overweight Korean adults. Int J Obes (Lond). 2012;36:281–5.
Trovato GM, Castro A, Tonzuso A, Garozzo A, Martines GF, Pirri C, et al. Human obesity relationship with Ad36 adenovirus and insulin resistance. Int J Obes (Lond). 2009;33:1402–9.
Trovato GM, Martines GF, Garozzo A, Tonzuso A, Timpanaro R, Pirri C, et al. Ad36 adipogenic adenovirus in human non‐alcoholic fatty liver disease. Liver Int. 2010;30:184–90.
Trovato GM, Martines GF, Trovato FM, Pirri C, Pace P, Garozzo A, et al. Adenovirus-36 seropositivity enhances effects of nutritional intervention on obesity, bright liver, and insulin resistance. Dig Dis Sci. 2012;57:535–44.
Almgren M, Atkinson R, He J, Hilding A, Hagman E, Wolk A, et al. Adenovirus-36 is associated with obesity in children and adults in Sweden as determined by rapid ELISA. PLoS One. 2012;7:e41652.
Lin WY, Dubuisson O, Rubicz R, Liu N, Allison DB, Curran JE, et al. Long-term changes in adiposity and glycemic control are associated with past adenovirus infection. Diabetes Care. 2013;36:701–7.
Tosh AK, Bray-Aschenbrenner A, El Khatib J, Ge B. Adenovirus-36 antibody status & BMI comparison among obese Missouri adolescents. Mo Med. 2012;109:402–3.
Berger PK, Pollock NK, Laing EM, Warden SJ, Hill Gallant K, Hausman DB, et al. Association of adenovirus 36 infection with adiposity and inflammatory-related markers in children. J Clin Endocrinol Metab. 2014;99:3240–6.
Karamese M, Altoparlak U, Turgut A, Aydogdu S, Karamese SA. The relationship between adenovirus-36 seropositivity, obesity and metabolic profile in Turkish children and adults. Epidemiol Infect. 2015;143:3550–6.
Laing EM, Tripp RA, Pollock NK, Baile CA, Della‐Fera MA, Rayalam S, et al. Adenovirus 36, adiposity, and bone strength in late‐adolescent females. J Bone Miner Res. 2013;28:489–96.
Parra-Rojas I, Moral-Hernández D, Salgado-Bernabé AB, Guzmán-Guzmán IP, Salgado-Goytia L, Muñoz-Valle JF. Adenovirus-36 seropositivity and its relation with obesity and metabolic profile in children. Int J Endocrinol. 2013;2013:e463194.
Sabin M, Burgner D, Atkinson R, Lee ZP-L, Magnussen C, Cheung M, et al. Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study. Int J Obes (Lond). 2015;39:1644–50.
Vander Wal JS, Huelsing J, Dubuisson O, Dhurandhar NV. An observational study of the association between adenovirus 36 antibody status and weight loss among youth. Obes Facts. 2013;6:269–78.
Cakmakliogullari EK, Sanlidag T, Ersoy B, Akcali S, Var A, Cicek C. Are human adenovirus-5 and 36 associated with obesity in children? J Investig Med. 2014;62:821–4.
Chang X, Yi J, Jian-Fei L, Ya-qun G. The regulation of adenovirus type 36 infection and progranulin expression in Uygur obese patients. J Xi’an Jiaotong Univ. 2015;36:219.
Ergin S, Altan E, Pilanci O, Sirekbasan S, Cortuk O, Cizmecigil U, et al. The role of adenovirus 36 as a risk factor in obesity: the first clinical study made in the fatty tissues of adults in Turkey. Microb Pathog. 2015;80:57–62.
Wang I, Lin L, Li T. Role of adenovirus infection and obese gene mutation in obestiy. Occup Health. 2008;24:2087–9.
Aldhoon-Hainerová I, Zamrazilová H, Atkinson RL, Dušátková L, Sedláčková B, Hlavatý P, et al. Clinical and laboratory characteristics of 1179 Czech adolescents evaluated for antibodies to human adenovirus 36. Int J Obes (Lond). 2014;38:285–91.
Voss JD, Burnett DG, Olsen CH, Haverkos HW, Atkinson RL. Adenovirus 36 antibodies associated with clinical diagnosis of overweight/obesity but not BMI gain: a military cohort study. J Clin Endocrinol Metab. 2014;99:E1708–12.
Sapunar J, Fonseca L, Molina V, Ortiz E, Barra MI, Reimer C et al. Adenovirus 36 seropositivity is related to obesity risk, glycemic control, and leptin levels in Chilean subjects. Int J Obes (Lond). 2019; https://doi.org/10.1038/s41366-019-0321-4.
Kocazeybek B, Dinc HO, Ergin S, Saribas S, Ozcabi BT, Cizmecigil U, et al. Evaluation of adenovirus-36 (Ad-36) antibody seropositivity and adipokine levels in obese children. Microb Pathog. 2017;108:27–31.
LaVoy EC, Arlinghaus KR, Rooney BV, Gupta P, Atkinson R, Johnston CA. High adenovirus 36 seroprevalence among a population of Hispanic American youth. Int J Adolesc Med Health. 2018; https://doi.org/10.1515/ijamh-2018-0110.
Tosh AK, Wasserman MG, McLeay II MT, Tepe SK. Human adenovirus-36 seropositivity and obesity among Midwestern US adolescents. Int J Adolesc Med Health. 2017; https://doi.org/10.1515/ijamh-2017-0126.
Waye MMY, Chan JCN, Tong PCY, Ma R, Chan PKS. Association of human adenovirus-36 with diabetes, adiposity, and dyslipidaemia in Hong Kong Chinese. Hong Kong Med J. 2015;21:45–7.
Zhou Y, Pan Q, Wang X, Zhang L, Xiao F, Guo L. The relationship between human adenovirus 36 and obesity in Chinese Han population. Biosci Rep. 2018;38:BSR20180553.
Pasarica M, Shin AC, Yu M, Yang HMO, Rathod M, Jen KLC, et al. Human adenovirus 36 induces adiposity, increases insulin sensitivity, and alters hypothalamic monoamines in rats. Obesity. 2006;14:1905–13.
Hwang KA, Park S, Ahn JH, Nam JH. Development of a standard protocol for quantitative polymerase chain reaction to detect adenovirus 36, which is associated with obesity. Acta Virol. 2018;62:350–9.
Krishnapuram R, Kirk-Ballard H, Zuberi A, Dhurandhar NV. Infectivity period of mice inoculated with human adenoviruses. Lab Anim. 2011;45:103–8.
Jiao Y, Aisa Y, Liang X, Nuermaimaiti N. Regulation of PPAR c and CIDEC expression by adenovirus 36 in adipocyte differentiation. Mol Cell Biochem. 2017;428:1–8.
Rathod M, Vangipuram SD, Krishnan B, Heydari AR, Holland TC, Dhurandhar NV. Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes. Int J Obes (Lond). 2006;31:78–86.
Rogers PM, Fusinski KA, Rathod MA, Loiler SA, Pasarica M, Shaw MK, et al. Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene. Int J Obes (Lond). 2007;32:397–406.
Vangipuram SD, Yu M, Tian J, Stanhope KL, Pasarica M, Havel PJ, et al. Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells. Int J Obes (Lond). 2006;31:87–96.
Na HN, Kim H, Nam JH. Novel genes and cellular pathways related to infection with adenovirus-36 as an obesity agent in human mesenchymal stem cells. Int J Obes (Lond). 2012;36:195–200.
Pasarica M, Mashtalir N, McAllister EJ, Kilroy GE, Koska J, Permana P, et al. Adipogenic human adenovirus Ad‐36 induces commitment, differentiation, and lipid accumulation in human adipose‐derived stem cells. Stem Cells. 2008;26:969–78.
Vangipuram SD, Sheele J, Atkinson RL, Holland TC, Dhurandhar NV. A human adenovirus enhances preadipocyte differentiation. Obes Res. 2004;12:770–7.
Wang ZQ, Yu Y, Zhang XH, Floyd EZ, Cefalu WT. Human adenovirus 36 decreases fatty acid oxidation and increases de novo lipogenesis in primary cultured human skeletal muscle cells by promoting Cidec/FSP27 expression. Int J Obes (Lond). 2010;34:1355–64.
Rathod MA, Rogers PM, Vangipuram SD, McAllister EJ, Dhurandhar NV. Adipogenic cascade can be induced without adipogenic media by a human adenovirus. Obesity. 2009;17:657–64.
Almgren M, Atkinson RL, Hilding A, He J, Brismar K, Schalling M, et al. Human adenovirus-36 is uncommon in type 2 diabetes and is associated with increased insulin sensitivity in adults in Sweden. Ann Med. 2014;46:539–46.
Dhurandhar NV, Dhurandhar EJ, Ingram DK, Vaughan K, Mattison JA. Natural infection of human adenovirus 36 in rhesus monkeys is associated with a reduction in fasting glucose. J Diabetes. 2014;6:614–6.
Rogers PM, Mashtalir N, Rathod MA, Dubuisson O, Wang Z, Dasuri K, et al. Metabolically favorable remodeling of human adipose tissue by human adenovirus type 36. Diabetes. 2008;57:2321–31.
Wang ZQ, Cefalu WT, Zhang XH, Yu Y, Qin J, Son L, et al. Human adenovirus type 36 enhances glucose uptake in diabetic and nondiabetic human skeletal muscle cells independent of insulin signaling. Diabetes. 2008;57:1805–13.
Krishnapuram R, Dhurandhar EJ, Dubuisson O, Kirk-Ballard H, Bajpeyi S, Butte N, et al. Template to improve glycemic control without reducing adiposity or dietary fat. Am J Physiol Endocrinol Metab. 2011;300:E779–9.
Blümer RME, van Roomen CP, Meijer AJ, Houben-Weerts JHPM, Sauerwein HP, Dubbelhuis PF. Regulation of adiponectin secretion by insulin and amino acids in 3T3-L1 adipocytes. Metabolism. 2008;57:1655–62.
Pereira RI, Leitner JW, Erickson C, Draznin B. Pioglitazone acutely stimulates adiponectin secretion from mouse and human adipocytes via activation of the phosphatidylinositol 3′-kinase. Life Sci. 2008;83:638–43.
Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002;8:1288–95.
Qatanani M, Lazar MA. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 2007;21:1443–55.
Na HN, Nam JH. Adenovirus 36 as an obesity agent maintains the obesity state by increasing MCP-1 and inducing inflammation. J Infect Dis. 2012;205:914–22.
Marseglia L, Manti S, D’Angelo G, Nicotera A, Parisi E, Di Rosa G, et al. Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci. 2014;16:378–400.
Moseti D, Regassa A, Kim WK. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int J Mol Sci. 2016;17:E124.
Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev. 2000;14:1293–307.
Furuhashi M, Saitoh S, Shimamoto K, Miura T. Fatty acid-binding protein 4 (FABP4): pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases. Clin Med Insights Cardiol. 2015;8:23–33.
Wu LE, Samocha-Bonet D, Whitworth PT, Fazakerley DJ, Turner N, Biden TJ, et al. Identification of fatty acid binding protein 4 as an adipokine that regulates insulin secretion during obesity. Mol Metab. 2014;3:465–73.
Xu H, Hertzel AV, Steen KA, Bernlohr DA. Loss of fatty acid binding protein 4/aP2 reduces macrophage inflammation through activation of SIRT3. Mol Endocrinol. 2016;30:325–34.
Lee YS, Kim J-w, Osborne O, Oh DY, Sasik R, Schenk S, et al. Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity. Cell. 2014;157:1339–52.
Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev. 2013;93:1–21.
Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes (Lond). 2009;33:54–66.
Jang MK, Son YH, Jung MH. ATF3 plays a role in adipocyte hypoxia-mediated mitochondria dysfunction in obesity. Biochem Biophys Res Commun. 2013;431:421–7.
Koh EH, Park JY, Park HS, Jeon MJ, Ryu JW, Kim M, et al. Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes. 2007;56:2973–81.
Sivitz WI, Yorek MA. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Signal. 2010;12:537–77.
Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004;101:15718–23.
Castaner O, Goday A, Park Y-M, Lee S-H, Magkos F, Shiow S-ATE, et al. The gut microbiome profile in obesity: a systematic review. Int J Endocrinol. 2018;2018:4095789.
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–31.
Koliada A, Syzenko G, Moseiko V, Budovska L, Puchkov K, Perederiy V, et al. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol. 2017;17:120.
Wasimuddin, Corman VM, Ganzhorn JU, Rakotondranary J, Ratovonamana YR, Drosten C, et al. Adenovirus infection is associated with altered gut microbial communities in a non-human primate. Sci Rep. 2019;9:13410.
Sang Y, Shields LE, Sang ER, Si H, Pigg A, Blecha F. Ileal transcriptome analysis in obese rats induced by high-fat diets and an adenoviral infection. Int J Obes (Lond). 2019; https://doi.org/10.1038/s41366-019-0323-2.
Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170:605–35.
McMurphy TB, Huang W, Xiao R, Liu X, Dhurandhar NV, Cao L. Hepatic expression of adenovirus 36 E4ORF1 improves glycemic control and promotes glucose metabolism through AKT activation. Diabetes. 2017;66:358–71.
Na HN, Dubuisson O, Hegde V, Nam JH, Dhurandhar NV. Human adenovirus Ad36 and its E4orf1 gene enhance cellular glucose uptake even in the presence of inflammatory cytokines. Biochimie. 2016;124:3–10.
Frese KK, Lee SS, Thomas DL, Latorre IJ, Weiss RS, Glaunsinger BA, et al. Selective PDZ protein-dependent stimulation of phosphatidylinositol 3-kinase by the adenovirus E4-ORF1 oncoprotein. Oncogene. 2003;22:710–21.
Dhurandhar EJ, Dubuisson O, Mashtalir N, Krishnapuram R, Hegde V, Dhurandhar NV. E4orf1: a novel ligand that improves glucose disposal in cell culture. PLoS One. 2011;6:e23394.
Yoon I, Park S, Kim R, Ko H, Nam J. Insulin-sparing and fungible effects of E4orf1 combined with an adipocyte-targeting sequence in mouse models of type 1 and type 2 diabetes. Int J Obes (Lond). 2017;41:1601–5.
Chang L, Chiang SH, Saltiel AR. Insulin signaling and the regulation of glucose transport. Mol Med. 2004;10:65–71.
Metz HE, Houghton AM. Insulin receptor substrate regulation of phosphoinositide 3-kinase. Clin Cancer Res. 2011;17:206–11.
Pessin JE, Saltiel AR. Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest. 2000;106:165–9.
Kusminski CM, Gallardo-Montejano VI, Wang ZV, Hegde V, Bickel PE, Dhurandhar NV, et al. E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte. Mol Metab. 2015;4:653–64.
Shastri AA, Hegde V, Peddibhotla S, Feizy Z, Dhurandhar NV. E4orf1: a protein for enhancing glucose uptake despite impaired proximal insulin signaling. PLoS One. 2018;13:e0208427.
Krishnapuram R, Kirk-Ballard H, Dhurandhar EJ, Dubuisson O, Messier V, Rabasa-Lhoret R, et al. Insulin receptor-independent upregulation of cellular glucose uptake. Int J Obes (Lond). 2013;37:146–53.
Na HN, Hegde V, Dubuisson O, Dhurandhar NV. E4orf1 enhances glucose uptake independent of proximal insulin signaling. PLoS One. 2016;11:e0161275.
Jinesh G, Sambandam V, Vijayaraghavan S, Balaji K, Mukherjee S. Molecular genetics and cellular events of K-Ras-driven tumorigenesis. Oncogene. 2018;37:839–46.
Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, Cristancho A, et al. PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev. 2008;22:2941–52.
Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, et al. PPARgamma signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19:557–66.
Zuo Y, Qiang L, Farmer SR. Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta during adipogenesis requires a peroxisome proliferator-activated receptor-gamma-associated repression of HDAC1 at the C/ebp alpha gene promoter. J Biol Chem. 2006;281:7960–7.
Madsen MS, Siersbaek R, Boergesen M, Nielsen R, Mandrup S. Peroxisome proliferator-activated receptor gamma and C/EBPalpha synergistically activate key metabolic adipocyte genes by assisted loading. Mol Cell Biol. 2014;34:939–54.
Armoni M, Harel C, Karnieli E. Transcriptional regulation of the GLUT4 gene: from PPAR-gamma and FOXO1 to FFA and inflammation. Trends Endocrinol Metab. 2007;18:100–7.
Puri V, Ranjit S, Konda S, Nicoloro SM, Straubhaar J, Chawla A, et al. Cidea is associated with lipid droplets and insulin sensitivity in humans. Proc Natl Acad Sci USA. 2008;105:7833–8.
Huh JY, Park YJ, Ham M, Kim JB. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells. 2014;37:365–71.
Lee YH, Pratley RE. The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diab Rep. 2005;5:70–5.
Park S, Park HL, Lee SY, Nam JH. Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity. Int J Obes (Lond). 2015;40:460–70.
Rull A, Camps J, Alonso-Villaverde C, Joven J. Insulin resistance, inflammation, and obesity: role of monocyte chemoattractant protein-1 (or CCL2) in the regulation of metabolism. Mediat Inflamm. 2010;2010:326580.
Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA. 2003;100:7265–70.
Na HN, Nam JH. Proof-of-concept for a virus-induced obesity vaccine; vaccination against the obesity agent adenovirus 36. Int J Obes (Lond). 2014;38:1470–4.
Na HN, Park S, Jeon HJ, Kim HB, Nam JH. Reduction of adenovirus 36-induced obesity and inflammation by mulberry extract. Microbiol Immunol. 2014;58:303–6.
Dhurandhar NV. A framework for identification of infections that contribute to human obesity. Lancet Infect Dis. 2011;11:963–9.
Kraakman MJ, Murphy AJ, Jandeleit-Dahm K, Kammoun HL. Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function? Front Immunol. 2014;5:470.
Castoldi A, Naffah de Souza C, Camara NO, Moraes-Vieira PM. The macrophage switch in obesity development. Front Immunol. 2015;6:637.
Fujisaka S, Usui I, Bukhari A, Ikutani M, Oya T, Kanatani Y, et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes. 2009;58:2574–82.
Cao Y. Angiogenesis as a therapeutic target for obesity and metabolic diseases. Chem Immunol Allergy. 2014;99:170–9.
Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121:2094–101.
Lin D, Chun TH, Kang L. Adipose extracellular matrix remodelling in obesity and insulin resistance. Biochem Pharmacol. 2016;119:8–16.
Blüher M. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance? Clin Sci (Lond). 2016;130:1603–14.
Gallagher KA, Joshi A, Carson WF, Schaller M, Allen R, Mukerjee S, et al. Epigenetic changes in bone marrow progenitor cells influence the inflammatory phenotype and alter wound healing in type 2 diabetes. Diabetes. 2015;64:1420–30.
Ishii M, Wen H, Corsa CA, Liu T, Coelho AL, Allen RM, et al. Epigenetic regulation of the alternatively activated macrophage phenotype. Blood. 2009;114:3244–54.
This work was supported by the Catholic University of Korea Research Fund 2019 to JHN; Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Science and ICT (NRF-2015M3A9B5030157 to JHN and NRF-2019R1A2C1086151 to JAK); and the KRIBB Research Initiative Program (to JAK). We thank Hae Li Ko for figure drawing.
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Kim, J., Na, H., Kim, JA. et al. What we know and what we need to know about adenovirus 36-induced obesity. Int J Obes 44, 1197–1209 (2020). https://doi.org/10.1038/s41366-020-0536-4
This article is cited by
Obesity Surgery (2021)
Insight into the relationship between obesity-induced low-level chronic inflammation and COVID-19 infection
International Journal of Obesity (2020)
Influence of adenovirus 36 seropositivity on the expression of adipogenic microRNAs in obese subjects
International Journal of Obesity (2020)