The Lipid-Sensor Candidates CD36 and GPR120 Are Differentially Regulated by Dietary Lipids in Mouse Taste Buds: Impact on Spontaneous Fat Preference

Abstract

BackgroundRecent studies in rodents and humans suggest that the chemoreception of long-chain fatty acids (LCFA) in oral cavity is involved in the spontaneous preference for fatty foods and might contribute to the obesity risk. CD36 and GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids raises the question of the respective role(s) played by these gustatory lipid-sensor candidates.Methodology/Principal FindingsUsing a combination of biochemical, nutritional and behavioural studies in wild-type, CD36+/−and CD36−/− mice, it was found that: 1°) CD36 and GPR120 display different diurnal rhythms in the gustatory circumvallate papillae, CD36 mRNA levels being down-regulated during the dark period in contrast to GPR120, 2°) this change is due to food intake and strictly dependent of the presence of lipids in the diet, 3°) CD36 protein levels are also rapidly but transiently decreased by the food intake, a two-fold drop in CD36 protein levels being found 1 h after refeeding, followed by a progressive return to the pre-prandial values, 4°) this down-regulation, which has a post-transcriptional origin, seems sufficient to alter the spontaneous fat preference, independently to change in the GPR120 gene expression.Conclusions/SignificanceIn contrast to GPR120, CD36 appears to be a food-sensitive lipid sensor in the gustatory circumvallate papillae. Lipid-mediated change in lingual CD36 expression might modulate the motivation for fat during a meal, initially high and then gradually decreasing secondary to the food intake. This short-term lipid-mediated effect is reminiscent of sensory-specific satiety. These findings, which highlight the role played by CD36 in the oro-sensory perception of dietary lipids, raise the possibility of novel pharmacological strategies to modify attraction for fatty foods and decrease obesity risks.

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

“…Consistent with this assumption, it was reported that the GLP-1 signaling modulates the sweet taste sensitivity ( 35 ). We recently reported that CD36 protein levels in mouse CVP is subjected to a highly sensitive short-term downregulation during food intake, in contrast to GPR120 ( 11 ). This regulation is strictly dependent on the presence of lipids in the diet.…”

“…In contrast, GPR120 was systematically detected in murine and human gustatory papillae ( 11,15,18 ) in which it was frequently coexpressed with CD36 ( 11,19 ). This last observation raises the question of the respective role(s) of these two LCFA receptors in the coding mechanisms eliciting the oro-sensory detection of dietary lipids at the periphery.…”

“…On the third day, mice were given mineral oil (Cooper, France) for both sessions so that the mice were not neophobic to the oily texture. On test days, animals were successively and randomly subjected to the control (mineral oil) or experimental (mineral oil + 0.5% OLA or 0.5% LA w/v; Sigma-Aldrich) solutions and the number of licks on each bottle was determined for 1 min from the fi rst lick to minimize post-ingestive signals ( 11 ). LA and OLA were tested on 2 different days.…”

Inhibition of the CD36 receptor reduces visceral fat accumulation and improves insulin resistance in obese mice carrying the BDNF-Val66Met variant

“…CD36 has been reported as a key factor in innate immunity and phagocytosis in resolution phase after ischemic stroke (9). In addition, CD36 uptakes long chain fatty acids and oxidized lipids, and has been identified as a fat sensing gustatory receptor in the taste buds (10)(11)(12). CD36 is also highly expressed in the duodeno-jejunum of small intestine, the main site of fat absorption (13).…”

Increased Levels of Extracellular Dopamine in the Nucleus Accumbens and Amygdala of Rats by Ingesting a Low Concentration of a Long-Chain Fatty Acid

“…A 19) and Laugerette et al 21) and Martin et al 34) have found no preference for fatty acids in CD36-deficient mice. These findings suggest the chemoreception of dietary fat via CD36 in the oral cavity.…”