Role in Obesity
AgRP induces obesity by chronic antagonism of the MC4-R. Overexpression of AgRP in transgenic mice (or intracerebroventricular injection) causes hyperphagia and obesity, whilst AgRP plasma levels have been found to be elevated in obese human males. Understanding the role AgRP plays in weight gain may assist in developing pharmaceutical models for treating obesity. AgRP mRNA levels have been found to be down regulated following an acute stressful event. Studies suggest that systems involved in the regulation of stress response and of energy balance are highly integrated. Loss or gain of AgRP function may result in inadequate adaptive behavioural responses to environmental events, such as stress, and may potentially contribute to the development of eating disorders. It has been shown that polymorphisms in the AgRP gene have been linked with anorexia nervosa as well as obesity. Some studies suggest that inadequate signalling of AgRP during stress may result in binge eating. Recent studies have shown that autophagy plays a key role in regulation of food intake and energy balance in maintaning neuronal AgRP levels.
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