Orexigenic

An orexigenic substance or signal stimulates appetite and food intake. In physiology and pharmacology, orexigenic means increasing hunger, often contrasted with anorexigenic, which suppresses appetite. Orexigenic drive results from signaling within the brain, especially the hypothalamus, and from peripheral hormones that act on feeding circuits.

Key mediators include neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus, which promote feeding when activated. Ghrelin, a stomach-derived hormone, robustly stimulates hunger by acting on these same neurons. Other orexigenic systems involve orexin (hypocretin) neurons in the lateral hypothalamus and melanin-concentrating hormone (MCH) neurons, as well as endocannabinoid signaling, all of which can enhance meal initiation and intake.

Mechanistically, orexigenic signals interact with brain reward and stress systems and project to other hunger centers such as the paraventricular nucleus, modulating motivation and meal size. Leptin and insulin generally exert anorexigenic effects, opposing orexigenic drives; the balance between these signals regulates energy intake and body weight.

Clinically, orexigenic strategies have been explored to counteract conditions like cachexia, chronic illness, or anorexia, though effectiveness and safety vary. Ghrelin agonists and other agents that stimulate appetite have been studied in research settings; cannabinoids, such as dronabinol, also exhibit orexigenic effects. Nutritional support and addressing underlying causes remain central to care.