Fat preference deficits and experience-induced recovery in global taste-deficient Trpm5 and Calhm1 knockout mice

Abstract

There is much evidence that gustation mediates the preference for dietary fat in rodents. Several studies indicate that mice have fat taste receptors that activate downstream signaling elements, including TRPM5 and CALHM1 ion channels and P2×2/P2×3 purinergic gustatory nerve receptors. Experiment 1 further documented the involvement of TRPM5 in fat appetite by giving Trpm5 knockout (KO) mice, which show global taste deficits, 24-h two-bottle choice tests with ascending concentrations of soybean oil (0.1 - 10% Intralipid) vs. water. Unlike wildtype (WT) mice, naive Trpm5 KO mice were indifferent to 0.5 - 2.5% fat. They preferred 5-10% fat but consumed much less than WT mice. The same KO mice preferred all fat concentrations in a second test series, which is attributed to a postoral fat conditioned attraction to the non-taste flavor qualities of the Intralipid, although they consumed less fat than the WT mice. The fat preference deficits of the Trpm5 KO mice were as great or greater than those observed in Calhm1 KO mice, another KO line with global taste deficits. Experiment 2 examined experience-enhanced fat preferences in Trpm5 KO and Calhm1 KO mice by giving them one-bottle training with 1%, 2.5%, and 5% fat prior to two-bottle fat vs. water tests. The KO mice displayed increased two-bottle preferences for all concentrations, although they still consumed less 1% and 2.5% fat than WT mice. Thus, the postoral actions of fat induce robust preferences for fat in taste-deficient mice, but do not stimulate the high fat intakes observed in WT mice with normal fat taste signaling.

Keywords: Fat taste; One-bottle exposure; Postoral fat appetition; Soybean oil; Two-bottle preference.

Fig. 1.

Experiment 1. Intake (means ± SE) of Intralipid and water for Trpm5 KO mice (n = 10, top) and WT mice (n = 10, middle) and percent fat preference for both groups (bottom) during 24-h Intralipid vs. water choice tests. In Test 1 (left) naive mice were tested with 0.1 – 5% Intralipid vs. water. In Test 2 (right), the same mice were retested with Intralipid vs. water. # Concentrations at which Intralipid intake significantly (p < 0.05) exceeded water intake within each group. * Concentrations at which WT and Trpm5 KO mice significantly (p < 0.05) differed in Intralipid intake or preference.

Fig. 2.

Experiment 2. Intake (+ SE) by Trpm5 KO (top), Calhm1 KO (middle) and WT (bottom) mice of 1%, 2.5% and 5% Intralipid and water during one-bottle training (Train, narrow bars) and two-bottle tests (wide bars). # Concentrations at which Intralipid intake significantly (P< 0.05) exceeded water intake within each group.

Fig. 3.

Experiment 2. Intake (+ SE) by Trpm5 KO (top), Calhm1 KO (middle) and WT (bottom) mice of 1%, 2.5% and 5% Intralipid and water during two-bottle tests of mice inexperienced (I) with one-bottle training and mice experienced (E) with one-bottle training. Data for inexperienced Trpm5 KO mice are from Experiment 1. Data for inexperienced Calhm1 KO mice are from [32] # Concentrations at which Intralipid intake significantly (P< 0.05) exceeded water intake within each group.