The p75 Neurotrophin Receptor is Necessary for Feeding and Survival in Leptin-Deficient Obesity

Eating disorders vary from eating far too little to far too much. The cause may be genetic, such as a deficiency of the hormone leptin, which communicates satiety, or environmental, such as the omnipresence of fatty junk foods (i.e. pizza at 2 am). We are investigating the p75 neurotrophin receptor (p75NTR) which can potentially address over and under eating from both homeostatic and pathological causes. Previously, we found that p75NTR is necessary for normal food intake following a fast, and that knockout of this receptor leads to significant weight loss following repetitive fasting. This led us to hypothesize that p75KO mice in high energy situations still consume less food than wildtype mice, and thus weigh less. When challenged with a high fat diet, our preliminary findings agree with a previously published study showing p75KO mice gain less weight, and we suggest that decreased food intake is part of the explanation. We find a more striking reduction in food intake and body weight when we knockout both p75NTR and either leptin or the leptin receptor. Furthermore, we find that p75NTR is necessary for survival without leptin signaling, with around 60% of mice dying by four months of age. These data suggest that p75NTR is necessary for normal feeding in high energy situations, and knockout of this receptor will prevent weight gain and induce weight loss through decreased food intake. With this new knowledge, we could potentially center treatments for disorders of feeding such as obesity and Anorexia around the p75NTR.