Investigating appetite control by G protein-coupled receptors

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

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Abstract

The purpose of this project is to understand the key cellular and neural circuit mechanisms by which pharmacological activation of G-protein coupled receptor (GPCR) signaling controls eating especially when foods are palatable and engage addiction-associated neural circuits. We hypothesize that GPCR signaling changes with chronic pharmacological anti-obesity treatment and that more precise combinations of pharmacological agents may enhance the efficacy of these treatments. We use quantitative fluorescence measurements including fluorescence lifetime of genetically encoded biosensors to track GPCR signaling over weeks in the same neuronal populations in awake behaving mice. We investigate how obesity and chronic anti-obesity treatments impact this GPCR signaling. This year, the lab made major progress in understanding the actions of GLP-1 and dopamine receptors during normal ingestion and during treatments with anti-obesity medications. We found important causal mechanisms by which GLP1R agonists mediate weight loss via neural circuits in the brainstem. We also uncovered a link between dopamine signaling in the amygdala and the motor actions of ingestion.