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.
Highlights
Long-term vagus nerve stimulation (VNS), characterized by intermittent delivery of a low-intensity electric current to the vagus nerve, has been introduced as an alternative add-on treatment for epilepsy
We have examined the effects of VNS on feed conversion efficiency, body weight, and adipose tissue metabolism in rats
To establish whether the decrease in Feed conversion efficiency (FCE) was the result of reduced fat absorption due to increased gastrointestinal tract motility, we measured the amount of fat and total fatty acids in feces because a small fraction of fat in the feces consists in biliary acids and cholesterol which do not influence calorie absorption
Summary
Long-term vagus nerve stimulation (VNS), characterized by intermittent delivery of a low-intensity electric current to the vagus nerve, has been introduced as an alternative add-on treatment for epilepsy Experience with this approach worldwide indicates that 40 to 50% of individuals with drug-resistant epilepsy show a .40% reduction in the number of seizures and that it is well tolerated, with only a few transitory side effects [1]. A small proportion of treated individuals has been found to experience weight loss [2,4,5,6], an effect that appears not to be related either to the antiepileptic action of VNS or to interaction between the prosthetic device and pharmacological treatments [6]. No data are so far available on whether stimulating the central nervous system by afferent fibers of the vagus nerve at the cervical level, as utilized for the antiepileptic action of VNS, the effect could be achieved indirectly by the combination of a topdown central effect on metabolism via reduced feed conversion efficiency
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