Session: SUN 0906-0926-Obesity and Inflammation
Poster Board SUN-0910
Objective: In this study, we examined the effect of fetal exposure to fluoxetine (Prozac®), a SSRI antidepressant, on hepatic lipid accumulation and markers of inflammation.
Methods: Female nulliparous Wistar rats were given vehicle (N=15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N=15) orally for 2 weeks prior to mating until weaning. We assessed liver histology, hepatic lipids and markers of inflammation in the offspring at 26 weeks of age.
Results: There was a significant increase in the number of offspring with mild to moderate NASH in FLX-exposed offspring relative to controls (p=0.04). The female offspring of FLX-treated dams had significantly higher levels of hepatic triglycerides and cholesterol (p<0.01); similar results were seen for male offspring although the cholesterol levels did not reach statistical significance (p=0.057). There was also evidence of increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in relative mRNA expression of TNFα (CON: 0.4 ± 0.22; FLU: 1.8 ± 0.58; p=0.02), IL-6 (CON: 0.2 ± 0.13; FLU 1.7 ± 0.52; p=0.003) and MCP1 (CON: 0.2 ± 0.13; FLU: 1.3 ± 0.45; p=0.008) whereas female offspring had higher expression of TNFα (CON: 0.8 ± 0.48; FLU: 2.5 ± 0.8; p=0.045), and increased macrophage infiltration (CD68; CON: 1.0 ± 0.09; FLU: 1.5 ± 0.06; p=0.01).
Conclusion: These data demonstrate that in this model fetal and neonatal exposure to FLX results in evidence of fatty liver and inflammation in both male and female offspring. Since fatty liver and hepatic inflammation are associated with a number of metabolic abnormalities, these results raise concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs.
Disclosure: HCG: Principal Investigator, Sanofi, Advisory Group Member, Sanofi, Consultant, Sanofi, Principal Investigator, Eli Lilly & Company, Advisory Group Member, GlaxoSmithKline, Advisory Group Member, Astra Zeneca, Advisory Group Member, Bristol-Myers Squibb, Principal Investigator, Roche Pharmaceuticals, Advisory Group Member, Novo Nordisk, Advisory Group Member, Boehringer-Ingelheim. Nothing to Disclose: NED, EB, CP, GW, DBH, KMM, VHT, ACH
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