Role of chemerin in hypothalamic control of feeding in rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 649-675-Central Regulation of Appetite & Feeding/GI Regulatory Peptides
Bench to Bedside
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-652
Luigi Brunetti*1, Chiara Di Nisio1, Lucia Recinella1, Sheila Leone2, Claudio Ferrante3, Rugia Shohreh3, Annalisa Chiavaroli3, Adriana Ricciuti4, Fabio Manippa5, Giustino Orlando5 and Michele Vacca5
1G. D'Annunzio University, Chieti, Italy, 2G.D'Annunzio University, Chieti, Italy, 3G. d'Annunzio University, Chieti, Italy, 4G. d'Annunzio University, Chieti, 5G.d'Annunzio University, Chieti
Context: Adipokines are adipose tissue-derived hormones which have been shown to modulate metabolic homeostasis. Chemerin, the natural ligand of the G protein-coupled receptor ChemR23, is a recently identified adipokine that could be involved in the regulation of adipogenesis, energy metabolism, and inflammation [1].

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.

[1] Roman AA et al., Endocrine 2012;42:243.

Nothing to Disclose: LB, CD, LR, SL, CF, RS, AC, AR, FM, GO, MV

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Supported by Italian Ministry of Education grant.