Effects of CCK-8 and GLP-1 on fatty acid sensing and food intake regulation in trout

Abstract

We hypothesize that cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) are involved in the modulation of metabolic regulation of food intake by fatty acids in fish. Therefore, we assessed in rainbow trout (Oncorhynchus mykiss) the effects of intracerebroventricular treatment with 1 ng/g of CCK-8 and with 2 ng/g of GLP-1 on food intake, expression of neuropeptides involved in food intake control and the activity of fatty acid-sensing systems in hypothalamus and hindbrain. Food intake decreased up to 24 h post-treatment to 49.8-72.3% and 3.1-17.8% for CCK-8 and GLP-1, respectively. These anorectic responses are associated with changes in fatty acid metabolism and an activation of fatty acid-sensing mechanisms in the hypothalamus and hindbrain. These changes occurred in parallel with those in the expression of anorexigenic and orexigenic peptides. Moreover, we observed that the activation of fatty acid sensing and the enhanced anorectic potential elicited by CCK-8 and GLP-1 treatments occurred in parallel with the activation of mTOR and FoxO1 and the inhibition of AMPKα, BSX and CREB. The results are discussed in the context of metabolic regulation of food intake in fish.

Integration of Nutrient Sensing in Fish Hypothalamus

“…CREB response to fatty acids was abolished by the presence of the CBP-CREB interaction inhibitor (Velasco et al, 2017b). Changes observed in CREB are comparable with those observed under other anorectic situations such as treatment with CCK o GLP-1 (Velasco et al, 2019). Moreover, increased levels of CREB occurred in zebrafish under the orexigenic conditions elicited by food deprivation (Craig and Moon, 2011).…”

“…In contrast, FoxO1 does not appear to respond to changes in the levels of leucine (Comesaña et al, 2018a(Comesaña et al, ,b, 2020. Other anorectic conditions also resulted in increased FoxO1 in rainbow trout as observed after treatment with CCK (Velasco et al, 2019), GLP-1 (Velasco et al, 2019), insulin (Blanco et al, 2020), ceramide (Velasco et al, 2016b(Velasco et al, , 2017a, or FFAR agonists (Velasco et al, 2020). Central changes in FoxO1 are comparable with those occurring in peripheral tissues under different feeding status.…”

“…There is no information available for BSX response in fish hypothalamus to the rise in amino acid levels. Other conditions known to decrease food intake in this species also decreased values for BSX as demonstrated by treatment with CCK (Velasco et al, 2019), GLP-1 (Velasco et al, 2019), or FFAR agonists (Velasco et al, 2020). No comparable studies assessed changes in Bsx mRNA expression under conditions of raised nutrient levels, not even in mammals.…”

“…A role for hypothalamic AMPKα in food intake control is also supported by the increase observed in hypothalamus of food-deprived rainbow trout (Conde-Sieira et al, 2019). The involvement of AMPK is further supported by the decrease in phosphorylation status of AMPKα observed in rainbow trout hypothalamus under anorectic conditions like treatment with ceramide (Velasco et al, 2016b(Velasco et al, , 2017a, FFAR agonists (Velasco et al, 2020), or anorectic hormones like CCK (Velasco et al, 2019), GLP-1 (Velasco et al, 2019), or insulin (Blanco et al, 2020). Of the different isoforms of AMPKα, it seems that AMPKα2 is involved in feed intake regulation while AMPKα1 appears to modulate peripheral metabolism (Conde-Sieira et al, 2019).…”

“…Additional studies relate mTOR to food intake regulation in fish. Thus, increased mTOR occurred under anorectic conditions like feeding a lipidenriched diet in rainbow trout (Librán-Pérez et al, 2015) and blunt snout bream (Dai et al, 2018) or different treatments in rainbow trout with PYY (Velasco et al, 2018), CCK (Velasco et al, 2019), insulin (Blanco et al, 2020), or ceramide (Velasco et al, 2017a). In other fish species, available information is limited.…”