Stimulation of sympathetic innervation in the upper gastrointestinal tract as a treatment for obesity

Abstract

SUMMARY Sympathetic activity and obesity have a reciprocal relationship. Firstly, hypothalamic obesity is associated with decreased sympathetic activity. Caffeine and ephedrine increase sympathetic activity and induce weight loss, of which 25% is due to increased metabolic rate and 75% is due to a reciprocally decreased food intake. Secondly, hormones and drugs that affect body weight have an inverse relationship between food intake and metabolic rate. Neuropeptide Y decreases sympathetic activity and increases food intake and body weight. Thirdly, a gastric pacemaker Transcend® and vagotomy increase the ratio of sympathetic to parasympathetic activation, decrease food intake, and block gut satiety hormones. Weight loss with the pacemaker or vagotomy is variable. Significant weight reduction is seen only in a small group of those treated. This suggests that activation of the sympathetic arm of the autonomic nervous system may be most important for weight loss. Systemic sympathetic activation causes weight loss in obese patients, but side effects limited its use. We hypothesize that selective local electrical sympathetic stimulation of the upper gastrointestinal tract may induce weight loss and offer a safer, yet effective, obesity treatment. Celiac ganglia delivers sympathetic innervation to the upper gastrointestinal tract. Voltage regulated electrical simulation of the rat celiac ganglia increased metabolic rate in a dose-dependent manner. Stimulation of 6, 3, or 1.5 V increased metabolic rate 15.6%, 6.2%, and 5%, respectively in a single rat. These responses support our hypothesis that selective sympathetic stimulation of the upper GI tract may treat obesity while avoiding side effects of systemic sympathetic activation.

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

“…Vagotomy or adrenalectomy reduced chow consumption in MSG rats; however, our findings suggest that interruption of vagus nervous activity plays a crucial role in food behavior compared with adrenal cortical activity. These data corroborate other previous studies in obese patients and animal obese models, which had reduced food intake when submitted to vagotomy (Cox et al 2004, Zheng et al 2009). Vagotomy prolongs gastric emptying and can affect the release of gastrointestinal hormones, such as ghrelin and glucagon-like peptide 1 (GLP1), which regulate orexigenic and anorexigenic hypothalamic neuropeptides.…”

Early Overfeed-Induced Obesity Leads to Brown Adipose Tissue Hypoactivity in Rats

“…Furthermore, the sympathetic splanchnic nerve stimulation has been suggested as a potential treatment for obesity because it reduces food intake and increases metabolic rate [38,39]. The present study, however, did not show changes in the sympathetic splanchnic nerve activity of SL rats, which may suggest that this nerve has little implication on sympathetic changes observed during obesity.…”

A Pilot Study to Evaluate the Effect of Splanchnic Nerve Stimulation on Body Composition and Food Intake in Rats

“…The safe stimulation currents were determined from the electrode impedance and the safe voltage parameters in our prior experiment [2]. The pulse width was 217 ms and 500 ms with an interphase delay of 500 ms. Stimulation frequency was set between 10 and 40 Hz.…”

“…Obesity driven by vagal overactivity as in hypothalamic obesity, however, is rare [2]. Based on the fact that most obesity has low sympathetic tone and a low ratio of sympathetic to parasympathetic activity, we postulated that stimulation of the sympathetic branch of the autonomic nervous system would be more effective in treating obesity than stimulation of the parasympathetic branch.…”

“…We have demonstrated that selective electrical stimulation of the celiac ganglia that innervates the upper gastrointestinal (GI) tract increases metabolic rate in a rat [2]. We chose a rodent model for it is much less expensive than the dog.…”