Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

作者：De Long Nicole E; Barry Eric J; Pinelli Christopher; Wood Geoffrey A; Hardy Daniel B; Morrison Katherine M; Taylor Valerie H; Gerstein Hertzel C; Holloway Alison C^*

来源：Toxicology and Applied Pharmacology, 2015, 285(1): 32-40.

DOI：10.1016/j.taap.2015.03.006

• Beta cell
• Inflammation
• Depression
• Adiposity
• Nonalcoholic steatohepatitis
• Dyslipidernia

Hypothesis: 10-15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown.
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 glucometabolic changes and hepatic pathophysiology in the offspring.
Results: Fluoxetine exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FIX-exposed offspring; males had significant elevations in TNF alpha, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNF alpha, and increased macrophage infiltration (MCP1).
Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy.
Conclusion: These data demonstrate that fetal and neonatal exposure to FIX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations.

• 出版日期2015-5-15