In FA transport and the response to a fat diet and specific defect in FA uptake in the proximal intestine of CD362/2 mice is associated with reduced incorporation of FA in TG and a diminished TG secretion. This concept was however AP24534 challenged. Published observations have shown that CD36 genetic deletion does not affect intestinal lipid uptake and the efficient participation of CD36 in LCFA intestinal uptake was questioned. It was suggested that CD36 functions as a FA sensor and stimulates events that control FA metabolism rather than being directly involved in the lipid transit. In any case, our findings show that small inhibitors of the CD36 binding functions can significantly reduce the postprandial BAY 73-4506 hypertriglyceridemia which follows a gastric olive challenge. Again, when compared to a complete deletion of the gene, which favor redundant mechanisms, a partial inhibition of CD36 functions may have different consequences. Our findings demonstrate that a selective down regulation of CD36 in the intestine reduces lipid intake and is beneficial to postprandial hypertriglyceridemia. In conclusion, CD36 is generally recognized as an important lipid and FA receptor which plays a role in the metabolic syndrome and its associated cardiac events. The pleiotropic activity and the various molecular associations of this scavenger in different cells and tissues have however questioned its potential as a safe therapeutic target. Different published observations have indeed suggested that CD36 down regulation might not been beneficial due to redundant mechanisms or potential toxicity. The present study shows that it is possible to identify small molecules that can block the CD36 binding and uptake functions and that such antagonism can reduce atherosclerosis, postprandial hypertriglyceridemia and be beneficial for type II diabetes. Particularly, elevated postprandial hypertriglyceridemia is a metabolic parameter which is now recognized to be strongly associated with cardiovascular events and is independent of traditional cardiovascular risk factors. Thus, CD36 might represent an attractive therapeutic target. Its expression can be induced by a broad spectrum of growth factors, hormones, or stress stimuli, and it is associated with various chronic conditions. Studies in mice have revealed that Mig-6 is required for skin morphogenesis and lung development and that it plays an important role in maintaining joint homeostasis. As a cytoplasmic scaffolding adaptor, MIG-6 has several important protein-protein interaction motifs that may mediate interaction with signaling molecules downstream of receptor tyrosine kinases. One of the most prominent roles of MIG-6 in regulating signal transduction comes from its ability to directly interact with epidermal growth factor receptor and other ErbB family members, inhibiting their phosphorylation and downstream signaling in a negative feedback fashion. MIG-6 can be induced by hepatocyte growth factor and functions as a negative feedback regulator of HGF-MET signaling, indicating that it has broad role as a signal checkpoint for modulating activated RTK pathways in a timely manner. The evidence that MIG-6 is a tumor suppressor gene is compelling. It is located in chromosome 1p36, a locus that frequently has loss of heterozygosity in several human cancers including lung cancer, melanoma, and breast cancer. Indeed, down-regulation or loss of MIG-6 expression has been reported in cancers and is often associated with poor prognosis. MIG-6 down-regulation in non-small cell lung cancer is associated with increased EGFR signaling and poorly differentiated cancer, while loss of its expression in ErbB2-amplified breast carcinoma renders the cancer cells more resistant to Herceptin, the neutralizing antibody against ErbB2.