High Fat Diet Does Not Compromise Vagal Afferent Responses to 5‐HT

Abstract

Endocrine cells lining the proximal intestine release 5-HT in response to ingested glucose which subsequently activates 5-HT3 receptors on vagal afferent nerve endings. Previous studies have suggested that glucose amplifies the response of dissociated vagal afferent neurons to 5-HT and that this effect is lost by exposure to a high fat diet (HFD). The aim of the present study was to determine if exposure to a HFD attenuates the ability of glucose to modulate the actions to 5-HT to excite gastric vagal afferent fibers in vivo. Male Sprague-Dawley rats were fed a control or HFD (14% or 60% kcal from fat) for 2 weeks. Then, rats were anesthetized with Inactin, and vagal afferent nerve activity was recorded from the anterior gastric vagal nerve using a bipolar electrode. Injection of 5-HT through a celiac arterial catheter evoked dose-dependent increases in vagal afferent nerve activity in both groups (Table 1) with no differences between rats fed control vs HFD. Acute hyperglycemia (400-500 mg/dL; IV infusion of 50% glucose for 10min) did not alter vagal afferent nerve responses to 5HT (3ug/kg) in control (baseline: 295±35% vs hyperglycemia: 289±33%) or HFD (baseline: 316±49% vs hyperglycemia: 291±31%) rats. These results suggest that HFD does not compromise the ability of vagal afferents to respond to 5-HT but, unlike dissociated vagal afferent neurons, extracellular glucose does not modulate this 5-HT-induced response. Further studies will be required to determine whether longer periods of elevated glycemia are required to modulate gastric vagal afferent responses. Table 1. Peak Change in Vagal Afferent Nerve Activity after 5-HT Injection *P<0.05 vs saline Saline 0.03 ug/kg 1 ug/kg 3 ug/kg 10 ug/kg Control (n=5) 113±2 148±11 * 183±16 * 274±29 * 297±38 * HFD (n=5) 116±5 137±11 * 183±18 * 250±22 * 313±19 *