GLP-1 Suppresses Feeding Behaviors and Modulates Neuronal Electrophysiological Properties in Multiple Brain Regions

Abstract

The glucagon-like peptide-1 (GLP-1) plays important roles in the regulation of food intake and energy metabolism. Peripheral or central GLP-1 suppresses food intake and reduces body weight. The electrophysiological properties of neurons in the mammalian central nervous system reflect the neuronal excitability and the functional organization of the brain. Recent studies focus on elucidating GLP-1-induced suppression of feeding behaviors and modulation of neuronal electrophysiological properties in several brain regions. Here, we summarize that activation of GLP-1 receptor (GLP-1R) suppresses food intake and induces postsynaptic depolarization of membrane potential and/or presynaptic modulation of glutamatergic or GABAergic neurotransmission in brain nuclei located within the medulla oblongata, pons, mesencephalon, diencephalon, and telencephalon. This review may provide a background to guide future research about the cellular mechanisms of GLP-1-induced feeding inhibition.

GLP-1 facilitates cerebellar parallel fiber glutamate release through PKA cascade in vitro in mice

“…GLP-1 regulates neuronal activity by modulating of multiple signal transduction, such as the ERK1/2, PKA, PKC and cytosolic Ca 2+ signaling pathways [11,18]. PKA signaling pathway plays a key role in regulating the synthesis and release of neurotransmitters, and activation of GLP-1 receptor can affect the release function of glutamate and regulate the release rate of neurotransmitter vesicles through cyclic adenosine phosphate-PKA signaling pathway [8,38].…”

“…GLP-1 regulates neuronal activity by modulating of multiple ion channels, such as calcium channels, nonselective cation channels, voltage-dependent potassium channels and TRPC5 channels [11]. GLP-1 induces depolarization of neuronal resting membrane potential and increase of cytosolic Ca 2+ , resulting in an increase in spike ring rate in rat nodose ganglion neurons [12].…”

“…GLP-1 can regulates neuronal activity by modulating of multiple signal transduction, such as the ERK1/2,protein kinase A (PKA),protein kinase C (PKC)and cytosolic Ca 2+ signal pathways [11,18].…”

GLP-1 enhances hyperpolarization-activated currents of mouse cerebellar Purkinje cell in vitro

“…GLP1 receptor activation is involved in regulating multiple ion channels and signaling pathways, such as calcium channels, non-selective cation channels, voltage-dependent potassium channels and TRPC5 channels, and protein kinase A (PKA) and protein kinase C signaling pathways ( Chen et al, 2021 ). GLP1 receptor activation can increase the level of cyclic adenosine monophosphate (cAMP) by activating adenylate cyclase, and subsequent activation of PKA.…”

“…GLP1 receptor activation increases intracellular Ca 2+ concentration through a Gq/11 pathway and recruits β-Arrestin to promote ERK1/2 signal transduction ( Wheeler et al, 1993 ; Koole et al, 2010 ). GLP1 receptor activation also inhibits adenosine 5′-monophosphate-activated protein kinase (AMPK) and activates mitogen-activated protein kinase (MAPK) in neurons through PKA signaling ( Hayes et al, 2011 ) and inhibits AMPK in the hindbrain and activates MAPK via protein kinase C signaling, thereby participating in the regulation of animal food intake ( Chen et al, 2021 ).…”