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

Abstract

Herein, we investigated whether subdiaphragmatic vagotomy has benefits on obesity, body glucose homeostasis, and insulin secretion in cafeteria (CAF)-obese rats. Wistar rats were fed a standard or CAF diet for 12 weeks. Subsequently, CAF rats were randomly submitted to truncal vagotomy (CAF Vag) or sham operation (CAF Sham). CAF Sham rats were hyperphagic, obese, and presented metabolic disturbances, including hyperinsulinemia, glucose intolerance, insulin resistance, hyperglycemia, and hypertriglyceridemia. Twelve weeks after vagotomy, CAF Vag rats presented reductions in body weight and perigonadal fat stores. Vagotomy did not modify glucose tolerance but normalized fed glycemia, insulinemia, and insulin sensitivity. Isolated islets from CAF Sham rats secreted more insulin in response to the cholinergic agent, carbachol, and when intracellular cyclic adenine monophosphate (cAMP) is enhanced by forskolin or 3-isobutyl-1-methylxanthine. Vagotomy decreased glucose-induced insulin release due to a reduction in the cholinergic action on β-cells. This effect also normalized islet secretion in response to cAMP. Therefore, vagotomy in rats fed on a CAF-style diet effectively decreases adiposity and restores insulin sensitivity. These effects were mainly associated with the lack of cholinergic action on the endocrine pancreas, which decreases insulinemia and may gradually reduce fat storage and improve insulin sensitivity.

Glucose Activates Vagal Control of Hyperglycemia and Inflammation in Fasted Mice

“…Previous studies showed that the pancreas is innervated by ‘sensory’ vagal fibers that may regulate insulin production through a sensory/efferent splanchnic network that involve other organs 29–34 . These results concur with other studies showing that innervations of the adrenal glands modulate hyperglycemia in hemorrhagic shock 35,36 . Thus, we analyzed whether vagal stimulation attenuates hyperglycemia in adrenalectomized endotoxemic mice.…”

“…Previous studies also showed that the pancreas is innervated by ‘sensory’ vagal fibers from the hepatic subdiaphragmatic branches and suggest that the vagus nerve may regulate insulin production through a complex sensory/efferent splanchnic network that involves other organs 29–34 . In agreement with these results, previous physiological studies showed that innervations of the adrenal glands modulate hyperglycemia in hemorrhagic shock 35,36 . Our current results show that efferent vagal stimulation induced insulin and adrenalectomy prevented vagal control of hyperglycemia in endotoxemia.…”

Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence

“…This suggests that vagotomy-induced reduction in insulin clearance is a phenomenon observed only in an obese mouse model, probably because they experienced malnutrition during early life. In fact, in nonprogramming obese rats, vagotomy also reduced insulin secretion but in contrast with our data, the insulinemia was reduced [ 24 ], which reinforces our idea that insulin clearance reduction induced by vagotomy may be dependent on metabolic programming. Although not evaluated, it seems that mice fed on a low-protein diet early in life followed by a regular diet in adulthood also develop decreased insulin clearance.…”

The Effect of Subdiaphragmatic Vagotomy on Lipid Profile and Insulin Resistance in Diabetic Obese Rats

“…After 5 weeks, the Lee obesity index of rats in the HFD group was calculated by dividing the cube root of BW (g) by nasoanal length (cm) and multiplying the result by 1000, and rats with lee obesity index greater than 310 were considered obese (17,19). were separated from the esophagus and cut off (19,21). After the operation, rats were received systemic analgesic (Ibuprofen 5mg/kg SC) for 3 days in order to decrease postoperative pain (22) and subcutaneous 10 cm glucose 5% (Figure 1).…”