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.

Background-The pathogenesis of unstable angina and non-Q-wave myocardial infarction is still poorly understood, and early evaluation of prognosis remains difficult. We therefore studied the predictive value of 5 biological indicators of inflammation, thrombogenesis, vasoconstriction, and myocardial necrosis, and we examined the effects of enoxaparin and unfractionated heparin on these markers after 48 hours of treatment. Methods and Results-Sixty-eight patients with unstable angina or non-Q-wave myocardial infarction randomized in the international ESSENCE trial participated in this French substudy. C-reactive protein, fibrinogen, von Willebrand factor antigen, endothelin-1 and troponin I were measured on admission and 48 hours later. The composite end point of death, myocardial infarction, recurrent angina, or revascularization was significantly lower at 14 and 30 days of follow-up in patients allocated to enoxaparin compared with unfractionated heparin. All acute-phase reactant proteins were elevated on admission and increased further at 48 hours. Multivariate analysis demonstrated that the rise of von Willebrand factor over 48 hours was a significant and independent predictor of the composite end point at both 14 days and 30 days. Moreover the early increase of von Willebrand factor was more frequent and more severe with unfractionated heparin than with enoxaparin (mean change was ϩ8.7Ϯ8.8% with enoxaparin versus ϩ93.9Ϯ11.7% with unfractionated heparin, PϽ0.0001). The other clinical and biological variables did not predict outcome. Conclusions-In patients with unstable angina or non-Q-wave myocardial infarction, the acute-phase proteins increase over the first 2 days despite medical treatment. The early rise of von Willebrand factor is an independent predictor of adverse clinical outcome at 14 days and at 30 days. Enoxaparin provides protection as evidenced by the reduced release of von Willebrand factor, which represents a favorable prognostic finding. (Circulation. 1998;98:294-299.)

BACKGROUND: Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses. METHODS: The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient's prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan-Meier method). RESULTS: CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2−/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR− (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8-92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5-17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18-3.75, triplenegative and HER2−/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2-8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50-0.64) for HER2+/ HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65-0.81) for HER2+/HR−, 4.4 months (HR = 1.55, 95% CI: 1.42-1.69) for triple-negative and 7.1 months for HER2−/HR+ patients (p <0.0001). CONCLUSIONS: Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients. CLINICAL TRIAL REGISTRATION: NCT03275311.

Glucagon-like peptide-1 (GLP-1) signaling modulates sweet-taste sensitivity in the mouse. Because circumvallate papillae (CVPs) express both GLP-1 and its receptor, a local regulation has been suggested. However, whether dietary lipids are involved in this regulation, as shown in the gut, is unknown. By using a combination of biochemical, immunohistochemical, and behavioral approaches, the present data i) confirm the role of GLP-1 signaling in the attraction for sucrose, ii) demonstrate that minute quantities of long-chain FAs (LCFAs) reinforce the attraction for sucrose in a GLP-1 receptor-dependent manner, iii) suggest an involvement of the LCFA receptor GPR120 expressed in taste buds in this system, and iv) support the existence of a regulation by GLP-1 of the lipid sensing mediated by lingual CD36. Therefore, oro-sensory detection of LCFAs may affect sweet and fatty taste responsiveness by controlling the secretion of lingual GLP-1. This regulatory loop, probably triggered by the LCFA-GPR120 interaction, might contribute to the high palatability of foods rich both in fat and sugar.