Vagal afferent cholecystokinin receptor activation is required for glucagon‐like peptide‐1–induced satiation

Abstract

Peripheral glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are secreted from enteroendocrine cells, and their plasma concentrations increase in response to eating. While the satiating effect of gut-derived CCK on food-intake control is well documented, the effect of peripheral GLP-1 is less clear. There is evidence that native GLP-1 can inhibit food intake only in the fed state but not in the fasting state.We therefore hypothesized that other gut peptides released during a meal might influence the subsequent effect of endogenous GLP-1 and investigated whether CCK could do so. We found that intraperitoneal injection of CCK in food-restricted mice inhibited food intake during the first 30-minute segment of a 1-hour session of ad libitum chow intake and that mice compensated by increasing their intake during the second half of the session. Importantly, this compensatory behaviour was abolished by an intraperitoneal injection of GLP-1 administered following an intraper-

Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake

“…In contrast to our hypothesis, patients with primary WL failure had similar GLP-1 and PYY concentrations after a fixed breakfast meal compared with patients with successful WL. Also, postprandial CCK concentrations did not differ between groups which is important since CCK receptor activation may be required for GLP-1 induced satiation, at least in rodents [ 26 ]. Fasting ghrelin concentration was lower in the primary WL failure group as also observed in previous WL response studies [ 14 , 18 , 19 ], consistent with the higher body weight [ 27 ], but the postprandial suppression of ghrelin did not differ between the groups contrasting with previous findings [ 10 , 14 , 18 , 19 ].…”

GLP-1 attenuates intestinal fat absorption and chylomicron production via vagal afferent nerves originating in the portal vein

“…We also recognize the potential of portal or nodose ganglia GLP-1Rs to be sensitizing vagal afferents to other circulating factors which regulate lipoprotein metabolism. Certainly, the reverse has been shown where pre-treatment with CCK in food-restricted mice can enhance the satiation effect of GLP-1 via a vagal afferent mechanism [ 30 ]. Regardless, experiments in our novel GLP-1R KO hamster model highlighted the importance of the GLP-1R in modulating the vagal response to GLP-1, as KO hamsters did not respond to portal or nodose ganglia injection of its native form.…”

Oral Erythritol Reduces Energy Intake during a Subsequent ad libitum Test Meal: A Randomized, Controlled, Crossover Trial in Healthy Humans

“…However, studies to date with erythritol and SGLT-1 are lacking. In addition, at least in mice, GLP-1 induced satiation requires vagal CCK receptor activation [ 48 ].…”