Document Detail

Immunomodulatory actions of central ghrelin in diet-induced energy imbalance.
MedLine Citation:
PMID:  21925262     Owner:  NLM     Status:  Publisher    
We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1β, IFN-γ) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1β, IL-6, IFN-γ, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-β remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1μg/day) for five consecutive days significantly reduced TNF, IL-1β and IFN-γ levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of IFN-γ, IL-17, IL-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways.
Darko Stevanovic; Vesna Starcevic; Urosh Vilimanovich; Dejan Nesic; Ljubica Vucicevic; Maja Misirkic; Kristina Janjetovic; Emina Savic; Dusan Popadic; Emina Sudar; Dragan Micic; Mirjana Sumarac-Dumanovic; Vladimir Trajkovic
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-8
Journal Detail:
Title:  Brain, behavior, and immunity     Volume:  -     ISSN:  1090-2139     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8800478     Medline TA:  Brain Behav Immun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Institute of Medical Physiology, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
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