Taken together, these experiments showed that Ad-36 enhanced differentiation of preadipocytes, which may be a contributory mechanism to its adipogenic effect in vivo. The lack of effect of Ad-2 on differentiation demonstrated that the observed findings were not a common characteristic of all adenoviruses. Future understanding of the molecular interactions of cellular and viral genes responsible for enhanced differentiation may reveal novel signaling pathways and controls of preadipocyte differentiation.

Objective: Human adenovirus Ad-36 causes adiposity in animal models and enhances differentiation and lipid accumulation in human and 3T3-L1 preadipocytes, which may, in part, explain the adipogenic effect of Ad-36. We determined the consequences of Ad-36 infection on leptin and glucose metabolism in fat cells. Design: 3T3-L1 preadipocytes were used to determine the effect of infection by human adenoviruses Ad-36, Ad-2, Ad-9 and Ad-37 on leptin secretion and lipid accumulation. Rat primary adipocytes were used to determine the effect of Ad-36 infection on leptin secretion and glucose uptake in vitro. Furthermore, the effect of Ad-36 on expressions of leptin and selected genes of de novo lipogenesis pathway of visceral adipose tissue were compared ex vivo, between Ad-36 infected and uninfected control rats. Results: Ad-36 suppressed the expression of leptin mRNA in 3T3-L1 cells by approximately 58 and 52% on days 3 and 5 postinfection, respectively. Leptin release normalized to cellular lipid content was 51% lower (Po0.002) in the Ad-36 infected 3T3-L1 cells. Lipid accumulation was significantly greater and leptin secretion was lower for the 3T3-L1 cells infected with other human adenoviruses Ad-9, Ad-36, or Ad-37. Whereas, human adenovirus Ad-2 did not influence cellular lipid accumulation or the leptin release. In rat primary adipocytes, Ad-36 reduced leptin release by about 40% in presence of 0.48 (Po0.01) or 1.6 nM insulin (Po0.05) and increased glucose uptake by 93% (Po0.001) or 18% (Po0.05) in presence of 0 or 0.48 nM insulin, respectively. Next, the adipose tissue of Ad-36 infected rats showed two to fivefold lower leptin mRNA expression, and 1.6-to 21-fold greater expressions for acetyl Co-A carboxylase-1 and 1.2-to 6.3-fold greater expressions for fatty acid synthase, key genes of de novo lipogenesis, compared to the uninfected weight and adiposity matched controls. Conclusion: The in vitro and ex vivo studies show that Ad-36 modulates adipocyte differentiation, leptin production and glucose metabolism. Whether such a modulation contributes to enhanced adipogenesis and consequent adiposity in Ad-36 infected animals or humans needs to be determined.

EtOH can significantly alter neural differentiation pathway-related gene expression and suppress Wnt signaling proteins in differentiating human NSC.

ETOH had no effect on NPC apoptosis but, resulted in more rapid coalescence and increased volume of neurospheres. Additionally, the expression of genes associated with cell adhesion was significantly altered. ETOH induced changes in NPC surface adhesion interactions may underlie aspects of neurodevelopmental abnormalities in FASD.