PMID- 23028630 OWN - NLM STAT- MEDLINE DCOM- 20130305 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 9 DP - 2012 TI - Vagus nerve stimulation reduces body weight and fat mass in rats. PG - e44813 LID - 10.1371/journal.pone.0044813 [doi] LID - e44813 AB - Among the manifold effects of vagus nerve stimulation (VNS) delivered as an add-on treatment to patients with drug-resistant epilepsy, a moderate loss of body weight has been observed in some individuals. We have now investigated this effect in rats. Exposure of rats to VNS for 4 weeks reduced feed conversion efficiency as well as body weight gain (by approximately 25%) and the amount of mesenteric adipose tissue (by approximately 45%) in comparison with those in sham-operated control animals. A pair-fed experiment showed that both lower dietary intake and increase energy expenditure independently contributed to the reduction of body weight and mesenteric adipose tissue. Moreover, VNS increased the level of non-esterified fatty acids in plasma and mesenteric adipose tissue by approximately 50 and 80%, respectively, without affecting that in the liver. In addition, VNS reduced the amounts of endocannabinoids and increased N-palmitoylethanolamide, an endogenous ligand of the transcription factor PPARalpha (peroxisome proliferator-activated receptor alpha) in mesenteric adipose tissue but not in the hypothalamus. These effects were accompanied by increased expression of the gene for brain-derived neurotrophic factor (BDNF) in the hypothalamus and up-regulation of the abundance of PPARalpha in the liver. Our results suggest that the reduction in body fat induced by VNS in rats may result from the action of both central and peripheral mediators. The reduced feed conversion efficiency associated with VNS may be mediated by hypothalamic BDNF, down-regulation of endocannabinoid tone in mesenteric adipose tissue and a PPARalpha-dependent increase in fatty acid oxidation in the liver, which in concerted action may account for the anorexic effect and increased energy expenditure. FAU - Banni, Sebastiano AU - Banni S AD - Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. banni@unica.it FAU - Carta, Gianfranca AU - Carta G FAU - Murru, Elisabetta AU - Murru E FAU - Cordeddu, Lina AU - Cordeddu L FAU - Giordano, Elena AU - Giordano E FAU - Marrosu, Francesco AU - Marrosu F FAU - Puligheddu, Monica AU - Puligheddu M FAU - Floris, Gabriele AU - Floris G FAU - Asuni, Gino Paolo AU - Asuni GP FAU - Cappai, Angela Letizia AU - Cappai AL FAU - Deriu, Silvia AU - Deriu S FAU - Follesa, Paolo AU - Follesa P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120928 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Endocannabinoids) RN - 0 (Fatty Acids, Nonesterified) RN - 0 (PPAR alpha) SB - IM MH - Adipose Tissue/*metabolism MH - Animal Feed MH - Animals MH - *Body Weight MH - Brain-Derived Neurotrophic Factor/genetics MH - Endocannabinoids/metabolism MH - Fatty Acids, Nonesterified/metabolism MH - Gene Expression Regulation MH - Hypothalamus/metabolism MH - Liver/metabolism MH - Male MH - PPAR alpha/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors MH - Vagus Nerve Stimulation/*adverse effects PMC - PMC3460935 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2012/10/03 06:00 MHDA- 2013/03/06 06:00 PMCR- 2012/09/28 CRDT- 2012/10/03 06:00 PHST- 2011/12/10 00:00 [received] PHST- 2012/08/14 00:00 [accepted] PHST- 2012/10/03 06:00 [entrez] PHST- 2012/10/03 06:00 [pubmed] PHST- 2013/03/06 06:00 [medline] PHST- 2012/09/28 00:00 [pmc-release] AID - PONE-D-11-24769 [pii] AID - 10.1371/journal.pone.0044813 [doi] PST - ppublish SO - PLoS One. 2012;7(9):e44813. doi: 10.1371/journal.pone.0044813. Epub 2012 Sep 28.