Sex differences in the ability of high fat diet to inhibit glucose‐induced modulation of 5‐HT3 receptor responses in GI‐vagal afferents in rats (905.4)

Previous studies in this lab have shown that extracellular glucose modulates 5‐HT3 receptor (5‐HT3R) mediated currents GI vagal afferent neurons and that this response is lost following exposure to a high fat diet (HFD). The aim of this study was to investigate whether this loss of glucose‐induced modulation showed any sex dependent differences. Sprague‐Dawley rats were placed on HFD (60% kcal from fat) at 28 days. Whole cell patch clamp recordings were made subsequently from acutely dissociated identified GI‐projecting vagal afferent neurons. The ability of extracellular glucose (2.5‐10mM) to modulate the magnitude of the 5‐HT‐induced inward current was assessed. After 4 weeks HFD exposure, glucose modulated the 5‐HT‐induced response in 7/8 neurons (87%) from female rats. In contrast, glucose modulated the 5‐HT‐induced inward current in only 4/7 neurons (57%; 4 weeks) from male rats (P<0.2). At this time point, there was no difference in body weights (male: 189±12g vs female: 168±5g; P>0.05) although male rats had significantly higher blood glucose levels (363±13mg/dl vs 251±7mg/dl; P<0.05). These data suggest that, following HFD (i) male rats may be more susceptible to loss of glucose‐induced modulation of 5‐HT‐induced currents in GI vagal afferent neurons and (ii) this loss of glucose‐induced modulation is determined primarily by dysregulated glycemic control rather than diet or obesity. Grant Funding Source : NIH DK078364, NSF IOS1148978