Role of infection in the pathogenesis of obesity
Authors:
Vojtěch Hainer 1; Irena Aldhoon Hainerová 1,2; Hana Zamrazilová 1
Authors‘ workplace:
Centrum pro diagnostiku a léčbu obezity, Endokrinologický ústav, Praha
1; Klinika dětí a dorostu, 3. lékařská fakulta UK a FN Královské Vinohrady, Praha
2
Published in:
Čas. Lék. čes. 2012; 151: 563-567
Category:
Review Article
Overview
Current global epidemic of obesity is mainly related to increased consumption of high energy density foods and sedentary lifestyle that leads to a positive energy balance with subsequent accumulation of fat stores, primarily in genetically predisposed individuals. However, additional pathogenetic factors should be considered, including an infection. Several viruses causing obesity have been described in mice, chicken, rats, hamsters and monkeys. In humans, a significant positive association between being overweight and IgG antibodies was found for Helicobacter pylori and Chlamydia pneumoniae. This association of bacterial infections with increased BMI might not represent a causal relationship but could be a marker for greater susceptibility of obese individuals to infection. Crucial role in the development of “infectious obesity“ in humans may be played by adenovirus infection, particularly AD-36 type that is also capable of inducing obesity in experimental animals as chicken, mice and monkeys. AD-36-induced obesity is paradoxically associated with lower levels of serum cholesterol and triglycerides both in humans and in experimental animals. Moreover, AD-36 enhances insulin sensitivity and improves hepatic steatosis. AD-36 effects in target organs as adipose tissue, liver and skeletal muscle are mediated through the viral protein E4orf1. This way AD-36 improves metabolic profile, as indicated by a greater glucose uptake by adipose tissue and skeletal muscle, reduced glucose output by hepatocytes, increased adiponectin levels and increased expression of adipogenic genes as peroxisome proliferator-activated receptor gamma. If E4orf1 improves glycemic control without reducing dietary fat intake and body fat stores, this viral protein would be highly valuable to develop novel anti-diabetic agents that mimic its effects.
Key words:
obesity, infection, adenovirus AD-36, diabetes mellitus, lipid profile, insulin sensitivity.
Sources
1. Hainer V, Bendlová B. Etiopatogeneze obezity. In: Hainer V, et al. Základy klinické obezitologie. Praha: Grada Publishing 2011; 59–90.
2. Mc Allister E, et al. Ten putative contributors to obesity epidemic. Crit Rev Food Sci Nutr 2009; 49(10): 868–913.
3. Dhurandar NV. Infectobesity: Obesity of infectious origin. J Nutr 2001; 131: 2794S–2797S.
4. Lyons MJ, et al. A virally induced obesity in mice. Science 1982; 216: 82–85.
5. Bernard A, et al. Alteration of leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus. J Virology 1999; 73: 7317–7327.
6. Griffond D, et al. Specific alteration of the expression of selected hypothalamic neuropetides during acute and late mouse brain infection using a morbilli virus: relevance to the late-onset obesity? Brain Res 2004; 1022: 173–181.
7. Carter JK, et al. Rous-associated virus type 7 induces a syndrome in chickens characterized by stunting and obesity. Infect Immun 1983; 39: 410–422.
8. Gosztonyi G, Ludwig H. Borna disease – neuropathology and pathogenesis. Curr Top Microbiol Immunol 1995; 190: 39–73.
9. Kim YS, et al. Scrapie-induced obesity in mice. J Infect Dis 1987; 156: 402–405.
10. Kim YS, et al. Adrenal involvement in scarpie-induced obesity. Proc Soc Exp Biol Med 1988; 189: 21–27.
11. Dhurandhar NV, et al. Avian adenovirus leading to pathognomic obesity in chickens. J Bombay Vet College 1990; 2: 131–132.
12. Dhurandhar NV, et al. Effect of adenovirus infection on adiposity in chickens. Vet Microbiol 1992; 31: 101–107.
13. Wigand R, et al. New human adenovirus (candidate adenovirus 36), a novel member of subgroup D. Arch Virol 1980; 64: 225–233.
14. Dhurandhar NV, et al. Adiposity in animals due to a human virus. In J Obes Relat Metab Disord 2000; 24: 989–996.
15. Dhurandhar NV, et al. Human adenovirus Ad-36 promotes weight gain in male rhesus and marmoset monkeys. J Nutr 2002; 132: 3155–3160.
16. Dhurandhar NV, et al. Transmisibility of adenovirus-induced adiposity in a chicken model. In J Obes 2001; 25: 990–996.
17. Švestka T, et al. Problematika infekce Helicobacter pylori u chorob žaludku a duodena. Čas. Lék. čes. 2004; 143: 734–737.
18. Fixa B. Úvahy o poklesu prevalence infekce Helicobacter pylori a vředové choroby v posledních dvou dekádách. Čas. Lék. čes. 2011; 150(2): 91–93.
19. Švestka T. Léčba infekce Helicobacter pylori u vředové choroby žaludku a duodena. Čas. Lék. čes. 2003; 142: 483–486.
20. Dart AM, et al. Association between past infection with Chlamydia pneumoniae and body mass index, low-density lipoprotein particle size and fasting insulin. Int J Obes Relat Metab Disord 2002; 26: 464–468.
21. Jaworowska A, Bazylak G. Chlamydophila pneumoniae antibodies may be independently associated with increased BMI and percentage of body fat among women. Int J Obes (Lond) 2011; 35: 1225–1232.
22. Ekesbo R, et al. Combined seropositivity for H. pylori and C. pneumoniae is associated with age, obesity and social factors. J Cardiovasc Risk 2000; 7: 191–195.
23. Thjodleifsson B, et al. Infections and obesity: A multinational epidemiological study. Scand J Infect Dis 2008; 40: 381–386.
24. Lajunen T, et al. The association of body mass index, waist and hip circumference and waist-hip ratio with Chlamydia pneumoniae IgG antibodies and high-sensitive C-reactive protein at 31 years of age in Northern Finland Birth Cohort 1966. Int J Obes (Lond) 2011; 35: 1470–1478.
25. Bil-Lula ID, et al. Improved real-time PCR assay for detection and quantification of 54 known types of human adenoviruses in clinical samples. Med Sci Monit 2012; 18: BR221–226.
26. de Jong JC, et al. Adenovirus 37: Identification and characterization of a medically important new adenovirus type of subgroup D. J Med Virol 1981; 7: 105–118.
27. Dhurandhar NV, et al. Association of adenovirus infection with human obesity. Obes Res 1997; 5: 464–469.
28. Atkinson RL, et al. Human adenovirus AD-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int J Obes (Lond) 2005; 29: 281–286.
29. Trovato GM, et al. Human obesity relationship with obesity and insulin resistance. Int J Obes (Lond) 2009; 33: 1402–1409.
30. Trovato GM, et al. AD36 adipogenic adenovirus in human non-alcoholic fatty liver disease. Liver Int 2010; 30(2): 184–190.
31. Atkinson RL, et al. Human adenovirus-36 antibody status is associated with obesity in children. Int J Pediatr Obes 2010; 5(2): 157–160.
32. Gabbert C, et al. Adenovirus 36 and obesity in children and adolescents. Pediatrics 2010; 126: 721–726.
33. Na HN, et al. Association between human adenovirus-36 and lipid disorders in Korean schoolchildren. Int J Obes (Lond) 2010; 34: 89–93.
34. Atkinson RL. Human adenovirus-36 and childhood obesity. Int J Pediatr Obes 2011; 6(Suppl1): 2–6.
35. Broderick MP, et al. Adenovirus 36 seropositivity is strongly associated with race and gender, but not obesity, among US military personal. Int J Obes (Lond) 2010; 34: 302–308.
36. Goossens VJ, et al. Lack of evidence for the role of human adenovirus-36 in obesity in a European cohort. Obesity (Silver Spring) 2011; 19: 220–221.
37. Atkinson RL. Prevalence of infection with adenovirus-36 in Belgium and Holland and association with obesity. Obesity (Silver Spring) 2011; 19(1): 2.
38. Salehian B, et al. Adenovirus 36 DNA in adipose tissue of patient with unusual visceral obesity. Emerg Infect Dis 2010; 16: 850–852.
39. Vangipuram SD, et al. A human adenovirus enhances preadipocyte differentiation. Obes Res 2004; 12: 770–777.
40. Pasarica M, et al. Adipogenic human adenovirus AD-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells. Stem Cells 2008; 26: 969–978.
41. Rathod MA, et al. Adipogenic cascade can be induced without adipogenic media by a human adenovirus Obesity (Silver Spring) 2009; 17: 657–664.
42. Rogers PM, et al. Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene. Int J Obes (Lond) 2008; 32: 397–406.
43. Bouwman JJM, et al. Infection-induced inflammatory response of adipocytes in vitro. Int J Obes (Lond) 2008; 32: 892–901.
44. 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: 914–922.
45. Jéquier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 2002; 967: 379–388.
46. Vangipuram SD, et al. Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells. Int J Obes (Lond) 2007; 31: 87–96.
47. Pasarica M, et al. Human adenovirus 36 induces adiposity, increases insulin sensitivity, and alters hypothalamic monoamines in rats. Obesity (Silver Spring) 2006; 14: 1905–1913.
48. Krishnapuram R, et al. Template to improve glycemic control without reducing adiposity or dietary fat. Am J Physiol Endocrinol Metab 2011; 300: E779–E789.
49. Dhurandhar EJ, et al. E4orf1: a novel ligand that improves glucose disposal in cell culture. PLoS One 2011; 6: e23394.
50. Trovato GM, et al. Adenovirus-36 seropositivity enhances effects of nutritional intervention on obesity, bright liver, and insulin resistance. Dig Dis Sci 2012; 57: 535–544.
51. Krishnapuram R, et al. Insulin receptor-independent upregulation of cellular glucose uptake. Int J Obes (Lond) 2012 Feb 7 (Epub ahead of print).
52. Trovato GM, et al. Obesity-independent association of human adenovirus Ad37 seropositivity with nonalcoholic fatty liver disease. J Clin Gastroenterol 2012; 46: e46–e54.
53. Wang ZQ, et al. Human adenovirus type 36 enhances glucose uptake in diabetic and nondiabetic human skeletal muscle cells independent of insulin signaling. Diabetes 2008; 57: 1805–1813.
54. Nedvídková J, et al. Adiponectin, an adipocyte-derived protein. Physiol Res 2005; 54(2): 133–140.
55. Rogers PM, et al. Metabolically favorable remodelling of human adipose tissue by human adenovirus type 36. Diabetes 2008; 57: 2321–2331.
Labels
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistArticle was published in
Journal of Czech Physicians
Most read in this issue
- Thalidomide epidemics – 50 years after
- Acute multiple organ failure after endoscopic polypectomy
- Role of infection in the pathogenesis of obesity
- Instruction to the Authors the Journal of Czech Physicians