In Western diet, about 40% of daily caloric intakes is lipid, despite the fact that the recommended level is 10% lower. This high-fat supply greatly contributes to the prevalence of obesity and associated diseases (i.e., non–insulin-dependent diabetes, atherosclerosis, and hypertension). In humans, studies showed that obese subjects prefer lipid when compared with lean subjects (1
), suggesting that inappropriate lipid perception might influence obesity risk by impacting feeding behavior.
The regulation of lipid intake is a complex phenomenon controlled by instantaneous orosensory stimuli (i.e., texture, odor, and taste) and delayed postingestive signals (3
). Until recently, the involvement of gustation in this phenomenon was neglected, dietary fat being thought to be detected only by trigeminal (texture perception) and retronasal olfactory cues (4
). However, short-term behavioral studies, in which normal and anosmic rodents were allowed to choose between oil- or xanthan-enriched solution (to mimic fat texture), strongly suggested that gustation plays a significant role in lipid perception (5
). Although dietary lipids consist mainly of triglycerides, compelling evidence from studies on the rat strongly suggests that long-chain fatty acids (LCFAs) may be responsible for the orosensory cue for fat. Indeed, adult animals exhibit a lower preference for triglycerides and short-chain fatty acids than for LCFAs (6
). Moreover, pharmacological inhibition of lingual lipase, the enzyme responsible for efficient LCFA release from dietary triglycerides, profoundly decreases preference for lipids (8
). Interestingly, lingual lipase level is especially high in the vicinity of taste buds, since it is locally secreted in the cleft of foliate and circumvallate papillae by the Ebner glands (8
). Such an anatomical design may be sufficient to generate an LCFA stimulus in taste receptor cells. In keeping with this assumption, unsaturated LCFAs were reported to inhibit, in rat taste bud cells, the delayed rectifying K+
channels known to be implicated in the transduction pathway of a variety of taste stimuli (9
). Moreover, rat lingual sensory epithelium expresses CD36 (also known as fatty acid transporter [FAT]) (11
), which binds LCFAs with an affinity in the nanomolar range (13
). The CD36 amino acid sequence predicts a ditopic glycoprotein with a large extracellular hydrophobic pocket (15
) between 2 short cytoplasmic tails. The C-terminal cytoplasmic tail has been shown to be associated with Src kinases (17
), suggesting an involvement of CD36 in cell signaling. Together, these data support the existence of a chemical perception of LCFAs in the oral cavity.
Literature on the physiological advantage(s) provided by such a putative orosensory detection system is scarce. A weak rise in the protein content of pancreatobiliary juice has been reported within 10 minutes after oral delivery of LCFAs in esophagectomized rats, suggesting that the presence of lipids in the oral cavity contributes to the cephalic phase of pancreatic secretions (18
). Findings demonstrate that tastant paired with fat intake can also influence lipid metabolic fate. Indeed, prolonged elevation in blood triglyceride was observed in rats in which a small amount of oil was directly administered onto the tongue before an intragastric feeding (19
). Longer-term metabolic changes have also been reported in healthy humans, in which a rise in plasma triglyceride level was observed 2 and 4 hours after a preloading with encapsulated oil (to avoid oral lipid exposure) followed by mastication and expectoration of lipid-enriched foods. This effect was lipid dependent, since no change was noticed with a lipid-free sham feeding (20
Although all these observations argue in favor of a taste for fat, the nature and physiological function(s) of an oral lipid sensor remain elusive. In the rat, CD36 appears to be a plausible candidate for this function. To explore this hypothesis, experiments were conducted both in rats and in wild-type and CD36-null mice. As the sensitivity to basic tastes is species specific (21
), expression of CD36 in papillae and surrounding nonsensory epithelium was first investigated and compared in mouse and rat. Then, impact of CD36 gene inactivation on short- and long-term fat preference and digestive secretions was explored. Data reported herein provide what we believe to be the first identification of a lipid sensor component in the oral cavity by demonstrating that lingual stimulation of CD36 by unsaturated fatty acids impacts both behavioral and digestive physiology.