ABSTRACT
The vagus nerve conveys gastrointestinal cues to the brain to control eating behavior. In obesity, vagally mediated gut-brain signaling is disrupted. Here, we show that the cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide synthesized proportional to the food consumed in vagal afferent neurons (VANs) of chow-fed rats. CART injection into the nucleus tractus solitarii (NTS), the site of vagal afferent central termination, reduces food intake. Conversely, blocking endogenous CART action in the NTS increases food intake in chow-fed rats, and this requires intact VANs. Viral-mediated Cartpt knockdown in VANs increases weight gain and daily food intake via larger meals and faster ingestion rate. In obese rats fed a high-fat, high-sugar diet, meal-induced CART synthesis in VANs is blunted and CART antibody fails to increase food intake. However, CART injection into the NTS retains its anorexigenic effect in obese rats. Restoring disrupted VAN CART signaling in obesity could be a promising therapeutic approach.
Subject(s)
Hyperphagia/genetics , Nerve Tissue Proteins/metabolism , Vagus Nerve/drug effects , Weight Gain/genetics , Animals , Humans , Male , RatsABSTRACT
Arterial sympathetic innervation (ASI) is a complex biological process requiring a fine axonal guidance by arteries. Its physiological impact has remained unknown for decades but recently started to be better understood and recognized. ASI is a key element of the adaptive response of the cardiovascular system to challenging situations (exposure to cold, exercise ) as ASI controls the diameter of resistance arteries, thus blood supply to organs and systemic arterial blood pressure via arterial tone modulation. Defaults in ASI can lead to diseases, acting as a main cause or as an aggravating factor. Its impact is actively studied in cardiovascular diseases representing major public health issues, like hypertension, but ASI could also play a role in aging and many more pathological processes including cancer.
TITLE: Les fonctions de l'innervation sympathique artérielle - Du développement à la pathologie. ABSTRACT: L'innervation sympathique artérielle (ISA) est un processus biologique complexe nécessitant un guidage fin des axones des neurones sympathiques par les artères. L'ISA est un élément clé de l'adaptation du système cardiovasculaire aux différentes contraintes (exposition au froid, exercice, etc.) : elle contrôle le diamètre des artères de résistance, donc le flux sanguin parvenant aux organes et la pression artérielle systémique via la modulation du tonus artériel. Son importance lors du vieillissement et dans de nombreux contextes pathologiques est de mieux en mieux reconnue et comprise. Son intégration à la prise en charge de nombreuses maladies (hypertension, cancer, etc.) permettrait d'en améliorer traitements et pronostic.
