Physiological Effect of Ghrelin on Body Systems

Figure 5

Effect of ghrelin on two main brain regions: arcuate nucleus (ARC) of the hypothalamus and the ventral tegmental area (VTA). The h-ghrelin is represented in the figure as a black amino acid sequence, and red-letter substitution is that of the rat. Acyl ghrelin is proposed to initiate neurocircuits that promote feeding behavior in the ARC and VTA. Within the ARC, ghrelin stimulates neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons by binding to GHSR on their surface. Upon activation, these neurons produce and release γ-aminobutyric acid which inhibits anorectic proopiomelanocortin (POMC) neurons, decreasing the release of the anorectic peptide α-melanocyte-stimulating hormone (α-MSH). This efficiently reduces the amount of α-MSH capable of binding to satiety promoting melanocortin 4 receptors (MC4Rs). Simultaneously, activated NPY/AGRP neurons increase their production and secretion of orexigenic peptides NPY and AGRP. NPY binds to neuropeptide Y receptor type 1 (Y1R), and AGRP antagonizes the binding of α-MSH at MC4Rs. These two effects, the reduction in anorectic and enhancement of orexigenic peptides, work to reduce the activity of second-order anorexigenic neurons in the paraventricular nucleus (PVN) to promote homeostatic feeding behavior [66]. Similarly, ghrelin also stimulates VTA DA neurons, increasing the frequency and probability of the DA release from their projections in the nucleus accumbens (NAcc), prefrontal cortex (PFC), hippocampus, and amygdala to encourage mesolimbic reward feeding [66].