It is estimated that 74% of adults in the United States are either overweight or obese, and over 10% have type 2 diabetes (T2D). Worldwide, T2D accounts for nearly 90% of the approximately 537 million individuals with diabetes. The number of those affected with T2D is growing at alarming rates in children and young adults (1, 2). Obese individuals have a higher risk of heart disease, stroke, sleep apnea, metabolic dysfunction–associated steatotic liver disease (MASLD), cancer, kidney failure, and premature death (1, 3). Obesity is a complex polygenic disease, but with no singular, prevalent obesity genes. Nonetheless, several consistent signaling pathways regulate feeding, satiety, and adipogenesis and control fat accumulation. Many involve signaling via GPCRs that control neuroendocrine processes. Mutations in several GPCRs, and notably those in the stimulatory G protein α subunit (Gαs) and specific adenylate cyclases, including ADCY3, are strongly linked to severe obesity (4–6). Many of these GPCRs respond to neuroendocrine peptides released in the feeding response to enable metabolic responses such as secretion of insulin or other neuropeptides. These factors can traffic via serum to the brain to activate neuronal receptors that suppress feeding. Particularly, in response to feeding, glucagon-like peptide 1 (GLP-1) is released by the intestinal lining and in turn accelerates insulin secretion and reduces glucagon secretion in pancreatic islets. GLP-1 also slows gastric emptying and regulates food intake. Notably, GLP1 receptor agonists are effective treatments for obesity and diabetes (1).