How Satiety Factors Reach CNS Appetite Centers

In this review we will consider how central structures involved in the regulation of energy balance gather information from the variety of different peripherally derived signaling molecules that we now believe provide an integrated perspective of energy status of the organism. The existence of the blood brain barrier means that the CNS is theoretically unable to directly monitor many of these circulating signals such as adiponectin, amylin, cholecystokinin (CCK), glucose, ghrelin, leptin, and peptide YY (PYY) which do not freely diffuse across this barrier. Studies have identified five primary mechanisms through which these circulating signals may transmit the afferent information they carry from the periphery to the CNS which we describe below. We will both discuss mechanisms and potential contributions of vagal afferent signaling, peptide transporters, vascular endothelial cell signaling, the arcuate nucleus of the hypothalamus, and brain structures which lack the blood brain barrier known as the sensory circumventricular organs (CVOs), in providing sensory information to the integrative centers of the hypothalamus and medulla which play such essential roles in the regulation of energy balance.