Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

Abstract

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca2+ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca2+ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

Vagotomy diminishes obesity in cafeteria rats by decreasing cholinergic potentiation of insulin release

“…Studies indicate that these vagal afferents are altered in obesity, which contributes to hyperphagia [10,12]. Consistent with these findings, truncal vagotomy has been shown to reduce food consumption in rodents [19,26] and humans [17]. Conversely, high-fat diet rats did not demonstrate any alteration in food intake after vagotomy or vagal de-afferentiation [31], similarly to our observations for food consumption in CAF Vag rats.…”

“…Although the pathophysiology of obesity is complex and not completely understood, several investigations using obese rodents or humans have demonstrated that the vagus nerve may contribute to obesity development and maintenance [3,4,17,19,30,31]. An increased PNS action, associated with reduced SNS activity, is implicated in fat deposition in hypothalamic, genetic, and high-fat diet-induced obesity [27,29,31].…”

“…An increased PNS action, associated with reduced SNS activity, is implicated in fat deposition in hypothalamic, genetic, and high-fat diet-induced obesity [27,29,31]. Accordingly, truncal vagotomy has been shown to be effective in promoting weight loss [3,4,17,19,31]. Here, we demonstrate that vagotomized CAF rats presented decreased BW, Lee index and perigonadal fat stores, in association with only a partial reduction in food consumption, since 12-h food intake in CAF Vag rats was similar to that of CAF Sham and CTL rats.…”

“…Different letters over the bars indicate significant differences. One-way ANOVA followed by the Tukey posttest, P < 0.05 Vagotomy has been shown to restore glucose tolerance in hypothalamic obesity [3,19]; however, benefits of vagotomy on body glucose control under high-caloric regimens have not been reported to date [31]. The mechanism of action by which PNS contributes to insulin action in peripheral tissues is not completely known.…”

“…The consumption of a CAF diet in rodents promotes obesity, hyperinsulinemia, glucose intolerance, and insulin resistance [2,28,34]. Despite the involvement of ANS dysfunction, more specifically PNS hyperactivity, in the development of hypothalamic, genetic and high-fat diet obesity has been often investigated [3,19,26,31]; no studies have reported the contribution of the PNS on CAF diet obesity. Therefore, we herein investigate the effects of subdiaphragmatic vagotomy on obesity, body glucose homeostasis, and insulin secretion in CAF-obese rats.…”