Chen CS, Bench EM, Allerton TD, Schreiber AL, Arceneaux KP 3rd, Primeaux SD. Preference for linoleic acid in obesity-prone and obesityresistant rats is attenuated by the reduction of CD36 on the tongue. Am J Physiol Regul Integr Comp Physiol 305: R1346-R1355, 2013. First published October 23, 2013 doi:10.1152/ajpregu.00582.2012.-Differential sensing of dietary fat and fatty acids by the oral cavity is proposed to regulate the susceptibility to obesity. In the current experiments, animals that differ in their susceptibility to obesity were used to investigate the influence of the oral cavity on the preference for the polyunsaturated fatty acid, linoleic acid. In experiment 1, the preference for differing concentrations of linoleic acid was determined in obesity-prone Osborne-Mendel (OM) and obesity-resistant S5B/Pl (S5B) rats. The preference threshold for linoleic acid was lower in S5B rats, compared with OM rats. To determine whether differences in linoleic acid preference threshold were related to innate strain differences in the fatty acid receptors on the tongue, the expression of GPR120, GPR40, and CD36 on the circumvallate papillae were assessed in OM and S5B rats. Results indicated that the expression of CD36, GPR40, and GPR120 did not differ between these two strains. Numerous studies have examined the role of CD36 on fat intake; therefore, in experiment 3, RNA interference was used to decrease the expression of CD36 on the tongues of OM and S5B rats, and the effect of decreased CD36 expression on linoleic acid preference was determined. CD36 siRNA attenuated linoleic acid preference for the most preferred concentration in both OM and S5B rats. Overall, these data indicate that there are innate differences in the preference threshold for linoleic acid in obesity-prone and obesity-resistant rats. Experimentally reducing the expression of CD36 on the circumvallate papillae attenuated the preference for linoleic acid in both strains. preference threshold; obesity-prone; obesity-resistant; CD36; taste CONSUMPTION OF AN ENERGY-DENSE, high-fat diet has been associated with an increased risk for developing obesity (23). The detection of dietary fat and subsequent fat intake are mediated by input from the oral cavity and by postingestive effects (12). The ability to sense dietary fat in the oral cavity has two main functions: 1) mediation of the cephalic phase response and 2) regulation of food intake (12, 31). Differences in fat/fatty acid sensors in the oral cavity have been proposed as potential mechanisms contributing to the susceptibility of becoming obese. This is characterized by a subset of individuals who become obese on a high-fat diet (HFD) and another subset of individuals that are resistant to becoming obese when consuming a HFD (15,24,31,33). Understanding the detection and regulation of fat intake by fat/fatty acid sensors in the oral cavity may elucidate the mechanisms by which individuals develop preferences for high-fat foods, overconsume dietary fat, and subsequently become obese.Demonstration...