Chronic high fat diet impairs glucagon like peptide-1 sensitivity in vagal afferents.

This study aimed to examine the effect of chronic high fat diet on GLP-1 sensitivity in vagal afferents. C57/BL6 mice were fed either a high-fat or low-fat diet for 6-8 weeks. To evaluate gastrointestinal afferent sensitivity and nodose neurons' response to GLP-1, extracellular afferent recordings and patch clamp were performed, respectively. Exendin-4 (Ex-4) was used as an agonist of the GLP-1 receptor. C-Fos Expression was examined as an indication of afferent input to the nucleus tractus solitarius (NTS). Food intake was monitored in real-time before and after Ex-4 treatment to monitor the consequence of the high fat diet on the satiating effect of GLP-1. In high fat fed (HFF) mice, GLP-1 caused lower activation of intestinal afferent nerves, and failed to potentiate mechanosensitive nerve responses compared to low fat fed (LFF). GLP-1 increased excitability in LFF and this effect was reduced in HFF neurons. Consistent with these findings on vagal afferent nerves, GLP-1 receptor stimulation given systemically, had a reduced satiating effect in HFF compared to LFF mice, and neuronal activation in the NTS was also reduced. The present study demonstrated chronic high fat diet impaired vagal afferent responses to GLP-1, resulting in impaired satiety signaling. GLP-1 sensitivity may account for the impairment of satiety signaling in obesity and thus a therapeutic target for obesity treatment. PMID: 32943186 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research