Adipogenic potential of multiple human adenoviruses in vivo and in vitro in animals

Abstract

Human adenovirus-36 (Ad-36) increases adiposity in chickens, mice, and nonhuman primates and is associated with human obesity. Ad-36 paradoxically reduces serum cholesterol and triglycerides in animal models. Ad-36 increases adipocyte differentiation and triglyceride accumulation in 3T3-L1 cells in vitro. This study evaluated whether three other human adenoviruses increase adiposity in chickens and in 3T3-L1 cells in vitro. We inoculated chickens with human Ad-2, Ad-31, Ad-37, or media at age 3 wk. Food intake and weights were recorded for 3.5 wk, and then chickens were killed and visceral fat, body composition, serum lipids, and viral antibody status were determined. Visceral fat and total body fat were significantly elevated (P < 0.001) in the Ad-37 group compared with all other groups. Final body weights were higher in chickens inoculated with Ad-37 compared with Ad-2, but not significantly higher than in control or Ad-31 groups. Food intake did not differ among groups. Serum cholesterol was elevated in Ad-37 chickens compared with control (P < 0.01) but was not affected by other viruses. Triglycerides were reduced in Ad-37 chickens (P < 0.0001) but were not affected by other viruses. In 3T3-L1 cells in vitro, Ad-31, Ad-36, and Ad-37, but not Ad-2, increased adipocyte differentiation and triglycerides accumulation. In summary, Ad-37 is another human adenovirus that increases adiposity and reduces serum triglycerides in an animal model. However, the response of serum cholesterol is opposite that of Ad-36. Evaluation of other human adenoviruses to determine their effects on adiposity and serum lipids is warranted, but in vitro assays may not be definitive for this purpose.

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

“…[1][2][3][4] As these initial reports, adipogenic potentials of more human adenoviruses, Ad-37 and Ad-5, have been reported. 6,15 Potential of various human adenoviruses to increase preadipocyte differentiation and cause adiposity may vary. Adenovirus-36, Ad-31, and Ad-37 increase rodent preadipocyte differentiation, 6 but Ad-31 is not associated with human obesity and the association of Ad-37 with human obesity is unclear.…”

“…6,15 Potential of various human adenoviruses to increase preadipocyte differentiation and cause adiposity may vary. Adenovirus-36, Ad-31, and Ad-37 increase rodent preadipocyte differentiation, 6 but Ad-31 is not associated with human obesity and the association of Ad-37 with human obesity is unclear. 1 Therefore, Greenway 16 recommended development of an in vitro assay that would correlates with association with human obesity for screening of adenovirus serotypes for their potential to induce human obesity.…”

“…5,6 Adenovirus type-2 produces lysis in A549 cells, but not in 3T3-L1 cells. Presence of its E1A expression A549 cells but not in 3T3-L1 cells suggested that Ad-2 does not replicate in 3T3-L1 cells, which may also explain the lack of its adipogenic effect.…”

“…[1][2][3][4] Inoculation of 3T3-L1 preadipocytes with Ad-36, but not Ad-2 (a nonadipogenic human adenovirus), resulted in increased adipocyte number, cellular lipid accumulation and glycerol 3-phosphate dehydrogenase levels (GPDH; an adipocyte differentiation specific enzyme marker) and modulation of several key cellular genes of differentiation. 5 The absence of adipogenic effect of Ad-2 in animals and cells 5,6 and a lack of association with human obesity 1 suggested that the lipogenic potential is not a common characteristic of all adenoviruses. The lipogenic effect of Ad-36 on preadipocytes may contribute to its adipogenic potential observed in vivo.…”

Infection-induced inflammatory response of adipocytes in vitro

“…8 Cytomegalovirus (CMV) and Chlamydia pneumoniae (Cp) are thought to be involved in the pathogenesis of atherosclerosis and cardiovascular disorders. [9][10][11][12][13][14] It has been shown before that adenoviruses (Ad) are able to infect adipocytes 15,16 and that this is possibly related to the development of obesity. 17,18 Data from studies in animals indicate a possible role for virus infections in the etiology of human obesity.…”