Increased innervation of the hypothalamic paraventricular nucleus by the AgRP and α-MSH axonal projections in germ-free mice

O. Vahirua^a (Mr), M. El Mehdi^a (Mrs), F. Zysk^a (Mr), S. Rabot^b (Dr), S. Fetissov*^a (Prof)

^a Rouen University, Mont-St-Aignan, FRANCE ; ^b Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-En-Josas, FRANCE

* Serguei.Fetissov@univ-rouen.fr

Background. Innervation of the paraventricular hypothalamic nucleus (PVN) by the orexigenic agouti-related protein (AgPR) and anorexigenic α-melanocyte-stimulating hormone (α-MSH) neurons of the arcuate nucleus (ARC), represents a key element in the appetite-regulating circuitry. Insufficient development of such circuitry has been found in mice with an early onset of anorexia and body weight loss. Recent studies also show that gut microbiota can be involved in regulation of feeding behavior by activation of both intestinal and central satiety pathways, while germ-free mice display increased food intake. Moreover, altered composition of gut microbiota is present in patients with anorexia and bulimia nervosa, the eating disorders which are 10 times more prevalent in females vs. males. However, it is unknown if the gut microbiota may influence the development of the ARC /PVN appetite circuitry. Objectives and Methods. To respond to this question, in the present study, we used immunohistochemistry to compare AgRP and α-MSH innervation of the PVN between germ-free and specific pathogen free 7-week-old C3H/HeN female mice. Results. We found that the germ-free mice display an increased innervation of the PVN by both AgRP and α-MSH fibers, but also, that the increase in the AgRP fiber density was about twice more important than that of α-MSH. Conclusions. These data reveal that gut microbiota may play an inhibitory role in the development in ARC/PVN axonal projections of AgRP and α-MSH neurons. It also suggests that a relative increase of PVN innervation by AgRP fibers may contribute to hyperphagia in germ-free mice.

Acknowledgement

The study was supported by the EC H2020 “GEMMA” and ERAnet “MIGBAN” research programs.

The author has declared no conflict of interest.