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.

Food entrains clock genes but not metabolic genes in the liver of suprachiasmatic nucleus lesioned rats

“…Here we demonstrate that in SCNx‐RF rats the expression of both genes exhibited robust diurnal fluctuations that persisted under fasting conditions; although PPARα showed modifications in its transcriptional profile probably due to an integration of the clockwork with the homeostatic information associated with the food deprivation state. This is clearly possible, considering that its expression is influenced by glucocorticoids [22] and the autonomic nervous system [23,24]. It is important to note that the relative expression of PPARα and Rev‐erbα in SCNx‐RF animals was remarkably coincident with that in the intact animals at the sampled time points, suggesting independence from other SCN related pathways, at least under the conditions tested.…”

Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System

“…Vagus nerve stimulation (VNS) is used as an add-on treatment to patients with drug-resistant epilepsy. Implantation of a vagus nerve stimulator in rats significantly decreased AEA and 2-AG in mesenteric adipose tissue, but increased PEA [128]. Chemical VNS by administration of the peptide hormone cholecystokinin 8 to fasted rats decreased expression of CB 1 in vagal afferent neurons [129].…”

BDNF mediates adaptive brain and body responses to energetic challenges

“…Vagus nerve stimulation tested in rats showed potential for treating metabolic disorders. ; during a 4-week period vagus nerve stimulation resulted in significant reductions in body weight and adipose tissue in rats, and these effects were accompanied by increased expression of BDNF in the hypothalamus [62]. However, this has not been tested in humans.…”