Abstract 285: Reduced Parasympathetic Activity and Correlation with Plasma Resistin Levels in High Fat Diet Mice

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A trait of most cardiovascular diseases, obesity, and aging is autonomic imbalance with increased sympathetic and decreased parasympathetic activity. While the hyperactive sympathetic nervous system has been extensively researched, little attention has been given to the mechanisms involved in the reduction of the parasympathetic nervous system. This study investigates the peripheral regulation of the parasympathetic nervous system and its association with plasma resistin levels in a high fat diet mice model of obesity. Male ICR mice were fed a high fat diet (HFD) or low fat diet (LFD) for 14 weeks. At the end of the diet regimen, mice underwent vagal stimulation (VS) tests and were sacrificed for blood and tissue collection. For VS, under anesthesia of intraperitoneal injection with urethane (2 g/kg), the right cervical vagus nerve was stimulated at 2 to 10Hz with pulses of 2ms and 2V while the heart rate was monitored with ECG. The reduction of heart rate by VS was significantly attenuated at 10Hz in HFD mice as compared to LFD mice (-121.3 beats per minute, 95% Confidence Interval [CI] -178 to -64.63, p<0.05, n=5 both groups). To evaluate the contribution of adipokines and cytokines to this reduced parasympathetic response, serum was tested using commercially available kits for resistin, adiponectin, TNFa, and IL6. Whereas no changes were observed in plasma adiponectin, TNFa, or IL6 levels, there was an significant increase in plasma resistin levels in HFD mice as compared to LFD mice (837 pg/mL, 95% CI 294-1379, p<0.01, LFD n=5, HFD n=4). Furthermore, a Pearson product-moment correlation coefficient was calculated to assess the relationship between plasma resistin level and responses in heart rate to VS. There was a strong positive correlation between these two variables (r=0.851, n=8, p<0.01). The molecular mechanisms responsible for the effects of resistin on the cholinergic, parasympathetic system are currently being investigated. In summary, these results suggest that elevated plasma resistin levels may contribute to a reduction in parasympathetic nervous system activity associated with obesity.