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

Abstract

In addition to orosensory signals, postoral 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 postoral 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 wild-type (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 postoral stimulation of appetite by fat but are not essential for oral fat preferences.

The oral lipid sensor GPR120 is not indispensable for the orosensory detection of dietary lipids in mice

“…This behavior is not gender-dependent as similar results were found in age-matched males and females (data not shown). Consistent with data from Sclafani et al ( 20 ), GPR120 Ϫ / Ϫ mice displayed an attraction to Intralipid similar to that of controls ( Fig. 2B ).…”

“…In contrast to prior results ( 15 ), a recent study reported that GPR120 Ϫ / Ϫ mice did not differ from wild-type mice in their preference for Intralipid ( 20 ), a fat emulsion composed of soy bean oil, egg phospholipids, and glycerin, suggesting that GPR120 might not be essential for oral fat detection. Although these two studies were conducted using the same GPR120 KO mouse model, a direct comparison between these two sets of data is difficult because of major differences in the lipid stimuli used, which were either free LCFAs ( 15 ) or lipid micelles ( 20 ). In another report, despite a specifi c activation of their afferent gustatory fi bers, wild-type mice were unable to detect and prefer nonfatty acid GPR120 agonists during behavioral tests ( 21 ).…”

“…In the present study, LCFA concentrations tested were deliberately limited to values reported as leading to signifi cant differences between controls and GPR120 Ϫ / Ϫ mice during two-bottle preference tests in ( 15 ), but remaining within the limits that may be found in the feed. Moreover, an infl uence of the KO mouse model used is unlikely because we found an attraction for Intralipid similar to the one found by Sclafani et al ( 20 ), whose ( 20,30 ), contrary to prior fi ndings ( 15 ). To further unravel the GPR120 role in the "taste of fat", we chose to revisit the effects of a GPR120 gene invalidation on taste bud functionality and lipid preference in mice.…”

“…Experimental solutions contained, in addition to xanthan gum, either 0.02%, 0.2%, or 2.0% rapeseed oil (w/v, Fleur de Colza, Lesieur, France), 0.5% or 1% LA, 2% sucrose (w/v), or 0.3 mM quinine (Sigma-Aldrich). In another set of experiments, Intralipid (20% Fresenius kabi a.b., Sweden) solutions were tested versus deionized water (0.25% and 2.5% Intralipid, v/v) ( 20 ). To avoid the development of side preferences, the position of each bottle was randomized and reversed for each test.…”

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

“…Studies utilizing transgenic mice suggest that intestinal GPR40 and GPR120 fatty acid sensors have critical roles in post-oral intake stimulation and preference conditioning by dietary fat 115 . The mechanisms underlying appetition are still being investigated but may involve other non-dopaminergic neurochemical systems and/or presently undiscovered hormonal mediators released from the gut mucosa.…”