Treating Diet-Induced Obesity: A New Role for Vagal Afferents?

As of the 2007–2008 National Health and Nutrition Examination Survey, 34% of adults—or over 72 million people—were obese, having a BMI [ 30. With childhood obesity catching up, this epidemic will only continue to grow for the foreseeable future. The current ‘‘obesogenic’’ environment characteristic of developed countries is often cited as the major cause of the obesity epidemic. Nevertheless, the observation that a large percentage of the population has not become obese could imply the contribution of a gene-environment interaction. For instance, the differential response to the obesogenic environment suggests one’s inherited physiological makeup (which itself is modulated by environment) either resists or favors obesity. Being obese might not be so unfortunate if weight gain and increased fat mass were the only consequences. Nonetheless, obesity is associated with numerous consequences such as diabetes, cardiovascular disease, and cancer [1], which in turn are related to proportionately large visceral abdominal fat stores [2]. Regrettably, no satisfactory non-invasive treatment for obesity has been developed. As a consequence, increasing numbers of expensive and risky bariatric surgical procedures, the only effective current therapies, are performed. Gastric bypass, though reasonably effective at reducing body weight, has been useful for treating type 2 diabetes [3]. The mechanism underlying these effects is not fully understood, but appears to involve decreases in consumption of high calorie foods, reductions of meal size and nutrient absorption, changes of anorexigenic and orexigenic hormone levels, increased energy expenditure, and altered vagal gastrointestinal (GI) innervation [4]. The key to the success of bypass in reducing body weight may thus be due to its effects on multiple organ systems. Before bariatric procedures became popular, truncal vagotomy, involving division of the right and left vagal trunks below the diaphragm was employed to treat morbid obesity [5]. Nonetheless, the interruption of vagal premotor axons as part of the vagotomy procedure caused gastric stasis and ‘‘dumping’’ of food from the stomach to the intestine, causing unpleasant sensations, including nausea. One way to overcome the adverse side effects of vagotomy and retain some of the benefits was to reduce or avoid damage to the vagal pre-motor axons. Indeed, selective sensory vagotomy may retain some of the benefits as it reduces food intake, body weight, and fat accumulation in rodent obesity models [6, 7]. Moreover, sensory vagotomy reduced the excess abdominal visceral fat found in aging rats [7]. Stearns et al. [8] took this approach further by distinguishing the effects of sensory vagotomy on different fat depots in rats subjected to diet-induced obesity (DIO). Sensory vagotomy was achieved by applying capsaicin to the abdominal vagal branches, and comparing the effect of this treatment on DIO in rats fed a high-energy ‘‘Western diet’’ for 11 months with the effects of truncal vagotomy and sham surgery. Interestingly, although sensory vagotomy non-significantly reduced body weight, it also modestly, but significantly and selectively, reduced visceral abdominal fat by 18% compared with controls. This is an important finding given the aforementioned association of central obesity with several causes of morbidity and mortality and since small changes in the size of the visceral fat depot can exert sizeable influences on overall mortality risk [9]. Stearns et al. [8] further suggested that sensory vagotomy could provide a valuable E. A. Fox (&) Behavioral Neurogenetics Laboratory, Ingestive Behavior Research Center, Department of Psychological Sciences, Purdue University, 703 Third Street, West Lafayette, IN 47907, USA e-mail: au_gc@psych.purdue.edu