427: Metformin decreases circulating inflammatory cytokines in a mouse model of obesity complicated by sFlt-1-induced preeclampsia


      Preeclampsia (PE) occurs in 3%–8% of all pregnancies and is a leading cause of maternal morbidity and mortality. Currently the only successful treatment for PE is delivery of the baby and placenta. Metformin, a biguanide medication, is used as treatment for type 2 diabetes and an acceptable oral agent for treatment of gestational diabetes. It has several mechanisms of action including targeting inflammatory, oxidative stress and vascular dysfunction pathways. Our hypothesis was that metformin reduces inflammation using an established obese mouse model of PE.

      Study Design

      Female CD-1 mice were fed high fat diet for 3 months, and then mated with CD-1 male. On day 1 of gestation, mice were randomly assigned to receive metformin (300 mg/kg, MET group) in drinking water or just plain drinking water (CTR group). On day 8 of gestation mice were injected with either adenovirus vector carrying sFl1 (AdsFlt1, 109 PFU/100 μL) or mFc (AdmFc, 109 PFU/100 μL as a virus control). Mice were sacrificed on day 18 of gestation and blood was collected. The levels of IL-6, Leptin, Insulin, Plasminogen activator inhibitor -1 (PAI-1), MCP-1, and Resistin were determined using Luminex® bead array. Data were analyzed using Student t-test or Mann-Whitney test as appropriate (significance was defined as p<0.05).


      Mice that received metformin had lower circulating levels of IL-6 and MCP-1 when compared to control mice (P=0.02 and P=0.04, respectively, Figure). There was no difference in the adipokines, leptin or resistin and no difference in circulating insulin or PAI-1 levels.


      Prophylactic administration of Metformin lowers the circulating pro-inflammatory cytokines IL-6 and MCP-1 in an obese mouse model of PE. Studies are ongoing to further investigate additional mechanisms by which metformin may ameliorate known dysfunctional pathways associated with PE.
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