Ghrelin Increases Energy Expenditure in Obese Rats Programmed By Changes in Perinatal Nutrition

Program: Abstracts - Orals, Poster Previews, and Posters
Session: SAT 542-571-Energy Balance: Control of Adiposity and Feeding
Basic
Saturday, March 7, 2015: 1:00 PM-3:00 PM
Hall D-F, Obesity (San Diego Convention Center)

Poster Board SAT-544

Health Disparities
Paula Beatriz Marangon, MSc, Jose Antunes-Rodrigues, MD, PhD and Lucila Elias, MD, PhD
School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil
Developmental programming can be defined as a stimulus during a critical period, when the central nervous system is still plastic and may show susceptibility to environmental effects. Ghrelin is a peptide expressed in the embryo since the morula stage and is able to increase cell proliferation in cells derived from different brain regions. Using the manipulation of litter size as a model of nutritional programming we investigated in male Wistar rats plasma ghrelin levels and the hypothalamic responsiveness to ghrelin. After birth, litters were adjusted as follows: small (3 pups-SL), normal (10 pups-NL) and large (16 pups-LL). Weaning was on day 21 and animals were kept in cages with standard rat chow. All experiments were performed on day 60 after birth. Blood samples were collected at 8 am for basal plasma ghrelin determination by Elisa. Animals were treated with ghrelin (40 µg/Kg ip) or saline at 5 pm. Food intake and body weight gain were evaluated 24h later. In another set, 60min after treatment, rats were decapitated and the mediobasal hypothalamus was dissected for p-AMPK and UCP-2 Western blotting analysis. Another set of animals was kept for 24h in individual metabolic cages, in order to record basal metabolic status. Thereafter, they were treated with either ghrelin or saline and data were obtained for another 24h. Finally, rats were decapitated and the brown adipose tissue (BAT) was collected. Data were analyzed using two-way ANOVA, followed by Tukey post-hoc test, or Student’s paired t-test. Difference was set at p<0.05 (n=8-12). SL animals had higher, whereas LL had lower body weight gain during lactation, compared to NL (NL:41.9±4.5g; SL:59.1±12.6g; LL:32.3±3.6g). SL rats maintained the increased body weight in adulthood, while LL rats reached the same body weight as NL ones at 60th day (NL:408.5±8.5g; SL:476.5±14.9g; LL:381.8±8.4g). Plasma acylated ghrelin (pg/mL) was increased in SL and LL rats, compared to NL (NL:27.4±1.3; SL: 39.2±3.1; LL: 36.7±2.4). After ghrelin treatment, NL rats increased food intake (11.1±0.4 g/100g bw vs 9.6±0.4), and body weight gain (12.3±1.1g vs 5.1±2.1), compared to saline treatment. Ghrelin was unable to modify food intake in SL rats (9.7±0.4 g/100g bw vs 9.7±0.4), but there was a reduction in body weight gain (2.6±2.0g vs 9.5±1.9), compared to the respective vehicle group. Ghrelin did not change food intake nor body weight gain in LL rats. In the hypothalamus, ghrelin increased p-AMPK only in NL rats and UCP-2 in NL and SL rats. There was an increase in VO2, VCO2, RER and indirect calorimetry after ghrelin treatment only in SL animals, compared to the basal condition. Also, there was an increase in UCP-1 in the BAT only in SL rats 24h after ghrelin treatment. Our data suggest that changes in food availability during neonatal life modify hypothalamic ghrelin responsiveness in obese animals in adulthood, with long lasting effects on energy homeostasis.

Nothing to Disclose: PBM, JA, LE

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Sources of Research Support: FAPESP; CNPq; CAPES