Human Adenovirus 36 Induces Adiposity, Increases Insulin Sensitivity, and Alters Hypothalamic Monoamines in Rats

Abstract

Objective: Human adenovirus 36 (Ad‐36) increases adiposity and reduces serum lipids in chicken, mouse, and non‐human primate models, and it is linked to obesity in sero‐epidemiological studies in humans. Involvement of the central nervous system (CNS) or adipose tissue in the mechanism of Ad‐36‐induced adiposity is unknown. The effects of Ad‐36 on adiposity and on the neuroendocrine system were investigated in a rat model. Research Methods and Procedures: Five‐week‐old male Wistar rats were inoculated intraperitoneally with Ad‐36 or medium. Results: Despite similar food intakes, infected rats attained significantly greater body weight and fat pad weight by 30 weeks post‐inoculation. Epididymal‐inguinal, retroperitoneal, and visceral fat pad weights of the infected group were greater by 60%, 46%, and 86%, respectively (p < 0.00001). The fasting serum insulin level and homeostasis model assessment index indicated greater insulin sensitivity in the infected group. Visceral adipose tissue expression of glycerol 3‐phosphate dehydrogenase, peroxisome proliferator‐activated receptor γ, and CCAAT/enhancer‐binding protein α and β was markedly increased in the infected animals compared with controls. Ad‐36 decreased norepinephrine levels significantly in the paraventricular nucleus in infected vs. control rats (mean ± standard error, 8.9 ± 1.1 vs. 12.8 ± 1.2 pg/μg protein; p < 0.05). Ad‐36 markedly decreased serum corticosterone in infected vs. control rats (mean ± standard error, 97 ± 41.0 vs. 221 ± 111 ng/mL; p < 0.005). Discussion: The results suggest that the pro‐adipogenic effect of Ad‐36 may involve peripheral as well as central effects. The male Wistar rat is a good model for the elucidation of metabolic and molecular mechanisms of Ad‐36‐induced adiposity.