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Adenovirus 36 DNA in Adipose Tissue | CDC EID
EID Journal Home > Volume 16, Number 5–May 2010
Volume 16, Number 5–May 2010
Adenovirus 36 DNA in Adipose Tissue of Patient with Unusual Visceral Obesity
Behrouz Salehian, Stephen J. Forman, Fouad R. Kandeel, Denise E. Bruner, Jia He, and Richard L. Atkinson
Author affiliations: City of Hope and Beckman Research Institute, Duarte, California, USA (B. Salehian, S.J. Forman, F.R. Kandeel); Denise Bruner and Associates, Arlington, Virginia, USA (D.E. Bruner); and Obetech Obesity Research Center, Richmond, Virginia, USA (J. He, R.L. Atkinson)
Suggested citation for this article
Massive adipose tissue depositions in the abdomen and thorax sufficient to interfere with respiration developed in a patient with multiple medical problems. Biopsy of adipose tissue identified human adenovirus 36 (Adv 36) DNA. Adv 36 causes adipogenesis in animals and humans. Development of massive lipomatosis may be caused by Adv 36.
Infection with human adenovirus 36 (Adv 36) has been reported to cause a large accumulation of fat in 4 animals (chickens, mice, rats, and monkeys) (1–3). Selective deposition of visceral fat disproportional to total fat deposition was observed in some studies. The increase in visceral fat or total body fat in infected animals compared with uninfected animals was >100% in some experiments (1–3). Of animals that were infected, 60%–100% became obese compared with uninfected animals (1–4). Obesity was defined as a weight or fat content greater than the 85th percentile of the uninfected animals.
Several human studies have shown a correlation of antibodies to Adv 36 and obesity (4–8). In 1 study of >500 persons, 30% of obese persons and 11% of lean persons had antibodies to Adv 36 (4). The body weight of infected persons was ≈25 kg heavier than that of uninfected persons (4). In 26 pairs of twins with discordant Adv 36 antibody status, infected twins were heavier and fatter (4). In a group of obese school children from South Korea, 30% had antibodies to Adv 36, and infected children had higher body mass index z-scores than uninfected children (5). However, in animals and adults in the United States, serum cholesterol and triglyceride levels were paradoxically reduced, despite the obesity (1–4). Recent reports of adults in Italy and children in South Korea support the association of Adv 36 and obesity, and show that Adv 36 is more common in obese persons; prevalence ranges from 29% to 65% (6,7).
The mechanisms responsible for the increased adiposity are changes in gene expression of multiple enzymes and transcription factors by the virus (8–15). In adipocytes, the sterol regulatory element binding protein pathway is increased, resulting in increases in levels of sterol regulatory element binding protein 1 and fatty acid synthase. Because levels of transcription factor CCAAT/enhancer binding protein-β, peroxisome proliferator-activated receptor-γ, and lipoprotein lipase are also increased, lipid transport into cells and fatty acid synthesis within cells is increased (8–15). In muscle cells, gene expression of glucose transporters Glut 1 and Glut 4 and phosphoinositide 3-kinase is increased, which results in noninsulin-mediated increases in glucose transport (14).
These changes are thought to be caused by the action of the Adv 36 open reading frame 1 early region 4 gene and may be blocked by small interfering RNA or the antiviral drug cidofovir (11,13). When the open reading frame 1 early region 4 gene was transferred to a retrovirus and inserted into preadipocytes in vitro, the gene was capable of inducing the enzymes and enhancing fat accumulation (13).
Adv 36 DNA persists in multiple tissues of infected animals for long periods after initial infection (3). Viral DNA was isolated from brain, lung, liver, muscle, and adipose tissue of monkeys 7 months after initial infection, long after the active virus has disappeared from blood and feces (3). The virus DNA apparently continues to alter gene expression chronically in tissues.
We report a patient with massive fat deposits in the thorax and abdomen. We postulate that these abnormal adipose tissue deposits were caused by Adv 36 infection.
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Adenovirus 36 DNA in Adipose Tissue | CDC EID
Suggested Citation for this Article
Salehian B, Forman SJ, Kandeel FR, Bruner DE, He J, Atkinson RL. Adenovirus 36 DNA in adipose tissue of patient with unusual visceral obesity. Emerg Infect Dis [serial on the Internet]. 2010 May [date cited]. http://www.cdc.gov/EID/content/16/5/850.htm