title: Vagus nerve stimulation reduces body weight and fat mass in rats.
abstract: 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 ∼25%) and the amount of mesenteric adipose tissue (by ∼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 ∼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 PPARα (peroxisome proliferator-activated receptor α) 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 PPARα 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 PPARα-dependent increase in fatty acid oxidation in the liver, which in concerted action may account for the anorexic effect and increased energy expenditure.
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. banni@unica.it
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Banni
authors.forename: Gianfranca
authors.initials: G
authors.lastname: Carta
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Murru
authors.forename: Lina
authors.initials: L
authors.lastname: Cordeddu
authors.forename: Elena
authors.initials: E
authors.lastname: Giordano
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.forename: Monica
authors.initials: M
authors.lastname: Puligheddu
authors.forename: Gabriele
authors.initials: G
authors.lastname: Floris
authors.forename: Gino Paolo
authors.initials: GP
authors.lastname: Asuni
authors.forename: Angela Letizia
authors.initials: AL
authors.lastname: Cappai
authors.forename: Silvia
authors.initials: S
authors.lastname: Deriu
authors.forename: Paolo
authors.initials: P
authors.lastname: Follesa
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D001835:Body Weight; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D063388:Endocannabinoids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D055536:Vagus Nerve Stimulation / Q000009:adverse effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D063388:Endocannabinoids; D005230:Fatty Acids, Nonesterified; D047493:PPAR alpha