OR38-2 Interaction of Prenatal Bisphenol-A Treatment and Postnatal Overfeeding on Insulin Sensitivity and Inflammatory Pathways in Visceral and Subcutaneous Adipose Tissue Depots

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR38-Physiological Impacts of Endocrine Disrupting Chemicals
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:30 AM
Room 256 (Moscone Center)
Almudena Veiga-Lopez*1, Kanakadurga Singer2, Carey N Lumeng2 and Vasantha Padmanabhan3
1Univ of Michigan Med Schl, Ann Arbor, MI, 2University of Michigan, Ann Arbor, MI, 3Univ of Michigan, Ann Arbor, MI
Epidemiological studies point to the impact of increased BPA exposure on adult pathologies, such as metabolic syndrome. Prenatal BPA induces insulin resistance and inhibits adiponectin release in rodents. Ongoing studies show that BPA induces hyperinsulinemia in pregnant sheep, a risk factor for metabolic disease in offspring. Obesity is associated with a pro-inflammatory state and development of insulin resistance. We hypothesized that 1) prenatal BPA induces insulin resistance that correlates with changes in adiponectin and inflammatory markers in adipose tissue and 2) postnatal obesity exacerbates these effects. Pregnant sheep were treated with 0.5mg of BPA/kg BW/day (30-90 of gestation, s.c.), in corn oil. Controls received vehicle only (C). Free BPA levels averaged 0.43±0.09 and 2.62±0.52ng/ml in umbilical cord blood of C and BPA-treated [n=6/group] day 60 fetuses, within range reported in human cord blood. At ~1.5 mo of age, about half of the C and prenatal BPA-treated female offspring were overfed (OF) to achieve BW (kg) of ~25% over the maintenance-fed group (C: 71.9±2; n=11, BPA: 71.3±3; n=9, COF: 88.7±4; n=11, and BPAOF: 88.8±2; n=12; at 15 mo of age). Intravenous glucose tolerance tests (IVGTT) were performed at 15 mo of age. Subcutaneous (SC) and visceral adipose tissues were collected at 22 mo of age for assessing expression of adiponectin and the macrophage marker, CD68 by qPCR. ANOVA followed by Bonferroni posthoc test revealed that both OF groups were hyperinsulinemic vs. maintenance-fed groups (P<0.05). Other IVGTT parameters did not differ amongst groups. Adiponectin was reduced (P<0.05) and CD68 increased (P<0.05) in the visceral depot of both OF groups relative to matching maintenance-fed groups and CD68 expression lower in BPAOF compared to COF (P=0.057). In the SC depot, prenatal BPA increased CD68 expression relative to the C group (P=0.02). Impact of postnatal weight gain on adiponectin was restricted to the BPA group (BPAOF vs. BPA; P=0.02). In conclusion, prenatal BPA had no effect on insulin homeostasis. Hyperinsulinemia seen in OF females may stem from reduced adiponectin and increased CD68 expression in the visceral fat depot. The selective elevation in CD68 in the SC, but not visceral depot of BPA females, and the differential impact of weight gain on CD68 expression in the visceral depot suggests that prenatal BPA and diet may interact to modulate inflammatory mechanisms within the two adipose tissue depots, differentially.

Nothing to Disclose: AV, KS, CNL, VP

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Sources of Research Support: Supported by NIH R01 ES16541 and P30 ES017885.