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GPR40 and GPR120 fatty acid sensors are critical for post-oral but not oral mediation of fat preferences in the mouse

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AJP Regulatory Integrative and Comparative Physiology

Published online on

Abstract

In addition to orosensory signals, post-oral actions of fat stimulate appetite and condition flavor preferences but the gut sensors mediating these responses are unknown. Here we investigated the role of the fatty acid sensors GPR40 and GPR120 in post-oral and oral preferences for a soybean oil emulsion (Intralipid). Mice were trained to drink a flavored solution (CS+) paired with intragastric (IG) oil infusions and another flavored solution (CS-) paired with water infusions. Knockout (KO) mice missing GPR40 or GPR120 sensors increased their CS+ intake in one-bottle tests (1 h/day) but less so than wildtype (WT) mice. The KO mice also preferred the CS+ to CS- in a two-bottle test but the preference was attenuated in GPR40 KO mice. Double knockout (DoKO) mice missing both GPR40 and GPR120 displayed attenuated stimulation of CS+ intake and only a marginal CS+ preference. The DoKO mice developed a more substantial CS+ preference when tested 24 h/day, although weaker than that of WT mice. The DoKO mice also consumed less of the CS+ paired with IG Intralipid as well as less Intralipid in oral tests. However, DoKO mice, like GPR40 KO and GPR120 KO mice did not differ from WT mice in their preference for Intralipid over water at 0.001% - 20% concentrations. In contrast to prior results obtained with mice missing the CD36 fatty acid sensor, these findings indicate that together GPR40 and GPR120 play a critical role in the post-oral stimulation of appetite by fat but are not essential for oral fat preferences.