Session: MON 649-675-Central Regulation of Appetite & Feeding/GI Regulatory Peptides
Bench to Bedside
Poster Board MON-652
Objectives:The aim of the present study was to investigate the effects of chemerin on food intake, body weight, and hypothalamic peptidergic and aminergic neurotransmitters which play a pivotal role in feeding regulation.
Design: Male adult Wistar rats, fed a standard laboratory chow diet (3.5% fat, 63% carbohydrate, 14% protein, 19.5% other components without caloric value; 3.20 kcal/g), were injected intraperitoneally, daily for 17 days at 0900 h, with either vehicle (saline; n=8) or chemerin (1.5 μg/rat; n=8). Food intake was recorded daily, and animals were sacrificed 24 h after the last injection. Total RNA was extracted from hypothalami and reverse transcribed to evaluate gene expression of agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). Furthermore, we evaluated the effects of chemerin on dopamine, norepinephrine and serotonin steady state concentrations in rat hypothalamus homogenate, and monoamine release from rat hypothalamic neuronal endings (synaptosomes), in vitro. Food intake, hypothalamic monoamine concentrations and gene expression data were analyzed by unpaired t test. Synaptosome monoamine release was statistically evaluated by analysis of variance (ANOVA) followed by Newman-Keuls comparison multiple test. The level of statistical significance was set as P<0.05.
Results: Intraperitoneal chemerin administration significantly decreased both food intake (P<0.05) and body weight (P<0.05) compared to vehicle. Chemerin treatment was associated with a significant reduction in AgRP (P<0.05) and orexin-A (P<0.05) mRNA levels, and a significant increase in serotonin steady state concentration (P<0.05) in the hypothalamus compared to control. Furthermore, chemerin stimulated serotonin release (P<0.0001) from synaptosomes, confirming a direct effect of chemerin on hypothalamic appetite-regulating pathways.
Conclusions: The anorexigenic effects of chemerin could be related to decreased AgRP and orexin-A gene expression and increased serotonin synthesis and release, in the hypothalamus.
Nothing to Disclose: LB, CD, LR, SL, CF, RS, AC, AR, FM, GO, MV
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