Melanocortin-4 receptors on neurons in the parabrachial nucleus mediate inflammation-induced suppression of food-seeking behavior

Anorexia is a common symptom during infectious and inflammatory disease. Here we examined the role of melanocortin-4 receptors (MC4Rs) in inflammation-induced anorexia. Mice with transcriptional blockage of the MC4Rs displayed the same reduction of food intake following peripheral injection of lipopolysaccharide as wild type mice but were protected against the anorexic effect of the immune challenge in a test in which fasted animals were to use olfactory cues to find a hidden cookie. By using selective virus-mediated receptor re -expression we demonstrate that the suppression of the food-seeking behavior is subserved by MC4Rs in the brain stem parabrachial nucleus, a central hub for interoceptive information involved in the regulation of food intake. Furthermore, the selective expression of MC4R in the parabrachial nucleus also attenuated the body weight increase that characterizes MC4R KO mice. These data extend on the functions of the MC4Rs and show that MC4Rs in the parabrachial nucleus are critically involved in the anorexic response to peripheral inflam-mation but also contribute to body weight homeostasis during normal conditions.

Automated summary

Anorexia is a common symptom during infectious and inflammatory disease. The study found that melanocortin-4 receptors (MC4Rs) play an important role in inflammation-induced anorexia. The experiments on mice with transcriptional blockage of the MC4Rs showed that they had the same reduction of food intake following peripheral injection of lipopolysaccharide as wild type mice, but were protected against the anorexic effect of the immune challenge in a test involving olfactory cues. By selectively re-expressing the receptors, it was demonstrated that MC4Rs in the brain stem parabrachial nucleus are responsible for the suppression of food-seeking behavior and also contribute to body weight homeostasis.