Post-oral fat-induced satiation is mediated by endogenous CCK and GLP-1 in a fat self-administration mouse model
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Post-oral fat-induced satiation is mediated by endogenous CCK and GLP-1 in a fat self-administration mouse model. / Vana, Vasiliki; Lærke, Michelle K.; Kleberg, Karen; Mroz, Piotr A.; Lindberg, Birgit L.; Ekberg, Jeppe H.; Rehfeld, Jens F.; Schwartz, Thue W.; Hansen, Harald S.
In: Physiology and Behavior, Vol. 234, 113315, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Post-oral fat-induced satiation is mediated by endogenous CCK and GLP-1 in a fat self-administration mouse model
AU - Vana, Vasiliki
AU - Lærke, Michelle K.
AU - Kleberg, Karen
AU - Mroz, Piotr A.
AU - Lindberg, Birgit L.
AU - Ekberg, Jeppe H.
AU - Rehfeld, Jens F.
AU - Schwartz, Thue W.
AU - Hansen, Harald S.
N1 - Publisher Copyright: © 2021
PY - 2021
Y1 - 2021
N2 - Triacylglycerol is the most abundant dietary lipid, and a strong stimulator of satiation. Absorption of triacylglycerol in the small intestine occurs in the form of free fatty acids and 2-monoacylglycerol, a process known to trigger not only the release of cholecystokinin (CCK) but also glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). It remains controversial, however, whether endogenously released GLP-1 and PYY are required for fat-induced satiation. Using a self-administration model where mice are trained to self-administer Intralipid 30% intragastrically, we show that blocking the CCK1 receptors with intraperitoneal devazepide diminishes the post-oral satiation effect of ingested fat. Similarly, s.c. administration of a GLP-1 receptor antagonist with a prolonged half-life (Jant4-C16) also reduced the post-oral satiation effect of ingested fat. Importantly, coadministration of the GLP-1 antagonist together with devazepide increased fat self-infusions to a level equal to the combined blockade of each individual peptide action alone, indicating an additive effect of endogenous CCK and GLP-1 in fat satiation signaling. Blocking the PYY Y2 receptor did not further enhance the fat intake in devazepide-treated mice. Consistent with the above, we show that voluntary post-oral ingestion of fat increases CCK and GLP-1 plasma levels and is correlated positively with CCK and GLP-1 plasma concentrations. Taken together, our results support the role of endogenous GLP-1 in the regulation of fat intake and suggest that both CCK and GLP-1 are required for the fat satiation signaling.
AB - Triacylglycerol is the most abundant dietary lipid, and a strong stimulator of satiation. Absorption of triacylglycerol in the small intestine occurs in the form of free fatty acids and 2-monoacylglycerol, a process known to trigger not only the release of cholecystokinin (CCK) but also glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). It remains controversial, however, whether endogenously released GLP-1 and PYY are required for fat-induced satiation. Using a self-administration model where mice are trained to self-administer Intralipid 30% intragastrically, we show that blocking the CCK1 receptors with intraperitoneal devazepide diminishes the post-oral satiation effect of ingested fat. Similarly, s.c. administration of a GLP-1 receptor antagonist with a prolonged half-life (Jant4-C16) also reduced the post-oral satiation effect of ingested fat. Importantly, coadministration of the GLP-1 antagonist together with devazepide increased fat self-infusions to a level equal to the combined blockade of each individual peptide action alone, indicating an additive effect of endogenous CCK and GLP-1 in fat satiation signaling. Blocking the PYY Y2 receptor did not further enhance the fat intake in devazepide-treated mice. Consistent with the above, we show that voluntary post-oral ingestion of fat increases CCK and GLP-1 plasma levels and is correlated positively with CCK and GLP-1 plasma concentrations. Taken together, our results support the role of endogenous GLP-1 in the regulation of fat intake and suggest that both CCK and GLP-1 are required for the fat satiation signaling.
KW - CCK1 receptor
KW - Fat
KW - GLP-1 receptor
KW - Jant4-C16
KW - Satiation
KW - Y receptor
U2 - 10.1016/j.physbeh.2021.113315
DO - 10.1016/j.physbeh.2021.113315
M3 - Journal article
C2 - 33460676
AN - SCOPUS:85102039085
VL - 234
JO - Physiology & Behavior
JF - Physiology & Behavior
SN - 0031-9384
M1 - 113315
ER -
ID: 262992211