State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis.

Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy homeostasis. Glucagon-like peptide-1 (GLP-1, encoded by ), secreted by a distinct population of neurons located within the nucleus tractus solitarius (NTS), suppresses feeding through projections to multiple brain targets. Although GLP-1 analogs are proven clinically effective in treating type 2 diabetes and obesity, the mechanisms of GLP-1 action within the brain remain unclear.

Hindbrain ghrelin and liver-expressed antimicrobial peptide 2, ligands for growth hormone secretagogue receptor, bidirectionally control food intake.

Hindbrain growth hormone secretagogue receptor (GHSR) agonism increases food intake, yet the underlying neural mechanisms remain unclear. The functional effects of hindbrain GHSR antagonism by its endogenous antagonist liver-expressed antimicrobial peptide 2 (LEAP2) are also yet unexplored. To test the hypothesis that hindbrain GHSR agonism attenuates the food intake inhibitory effect of gastrointestinal (GI) satiation signals, ghrelin (at a feeding subthreshold dose) was administered to the fourth ventricle (4V) or directly to the nucleus tractus solitarius (NTS) before systemic delivery of the GI satiation signal cholecystokinin (CCK).

Nucleus of the solitary tract A2 neurons control feeding behaviors via projections to the paraventricular hypothalamus.

Hindbrain NTS neurons are highly attuned to internal physiological and external environmental factors that contribute to the control of food intake but the relevant neural phenotypes and pathways remain elusive. Here, we investigated the role of NTS A2 neurons and their projections in the control of feeding behaviors. In male TH Cre rats, we first confirmed selective targeting of NTS A2 neurons and showed that chemogenetic stimulation of these neurons significantly suppressed dark cycle food intake, deprivation re-feed and high fat diet intake.

Growth differentiation factor 15 (GDF15) and semaglutide inhibit food intake and body weight through largely distinct, additive mechanisms.

Aims: To evaluate whether the potent hypophagic and weight-suppressive effects of growth differentiation factor-15 (GDF15) and semaglutide combined would be a more efficacious antiobesity treatment than either treatment alone by examining whether the neural and behavioural mechanisms contributing to their anorectic effects were common or disparate.

Materials/methods: Three mechanisms were investigated to determine how GDF15 and semaglutide induce anorexia: the potentiation of the intake suppression by gastrointestinal satiation signals; the reduction in motivation to feed; and the induction of visceral malaise. We then compared the effects of short-term, combined GDF15 and semaglutide treatment on weight loss to the individual treatments.