Obesity prevalence continues to climb worldwide providing significant pathophysiologic challenges to human health. Hyperphagia, the primary driver of this epidemic, results from the activating effects of hedonic sensory features of the food environment on specific, behavior-generating brain circuits. Feeding inhibition, by contrast, results from ingested food triggering GI satiation signals whose activational effects are conveyed via vagal afferents and processed by n. tractus solitarious (NTS) neurons that are also responsive to leptin and oxytocin. A focus on food intake inhibition neurobiology compels attention to roles for gastrointestinal satiation signals and provides an entry point in deciphering a circuit diagram for feeding inhibition that should be useful to the development of efficacious obesity phramacotherapies. It is interesting to note that GLP-1 released from intestinal enteroendocrine cells by digested food excites centrally projecting vagal afferents that in turn excite GLP-1-positive TH- positive and PrRP-positive NTS neurons. The rats’ ~500 GLP-1 NTS neurons send their axons to multiple and anatomically distributed GLP-1R expressing nuclei such that when activated by the consequences of food ingestion and other antecedents there is a brain wide increase in GLP-1R signaling that results in feeding inhibition. Others and we have individually probed function in various GLP-1R expressing nuclei with agonist and find a remarkable degree of redundancy across targets including reductions in: meal size, cumulative intake, food seeking and feeding motivation. GLP-1R targeted anti-obesity drug therapy works via brain penetrance of long acting modied agonists resulting in multisite activation of endogenous control circuits to reduce feeding and thereby body weight. Among their actions GLP-1R targeting therapies impact neural mediation of hedonic processes involved in food seeking and feeding motivation. Support from NIH DK-21397