Evidence for Involvement of the Cysteinyl Leukotriene Type 2 Receptor (CysLT2R) in the Regulation of Food Intake and Body Weight and Possible Role for Vagal Afferents
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The field of food intake and satiety has received increasing interest from the research community in recent years. The mechanisms and factors that regulate satiety gains their importance from the crucial role they play in food consumption and consequently control of body weight. Leukotrienes are mediators that are released in inflammatory conditions. One of the receptors on which Leukotrienes perform their actions is Cysteinyl Leukotriene Receptor Type 2 (CysLT2Rs). Recently, our colleagues made the observation that CysLT2Rs are expressed in vagal afferent neurons. In addition, CysLT2R-/- mice appeared to be heavier than WT (Moos and Funk, unpublished observations). Based on these findings, I hypothesized that CysLT2Rs play a role in regulating food intake via vagal afferent activity. In-vivo studies were performed to characterize body weight gain and investigate whether weight gain was associated with increased food intake. I found that CysLT2R-/- mice not only have significantly higher body weight, but also eat significantly more than CysLT2R+/+ mice. Using calcium imaging techniques, I demonstrated that LTD4 and LTC4 increased calcium Ca2+ influx in nodose ganglion neuron. Moreover, the level of neuronal activation in the brainstem (NTS area) was measured in both groups of mice using immunohistochemical techniques, which suggested less postprandial neuronal activity in KO mice. These data suggest that CysLT2Rs take part in regulating body weight and food intake. In addition these results implicate vagal afferents as a possible pathway. These findings may have implications for the control of food intake in both health and disease and may lead to novel insights in the causes and treatment of disordered weight such as overweight and obesity, or even anorexia.