COMPARISON OF THE LIPID‐LOWERING EFFECTS OF NICOTINIC ACID AND 2,5‐DIMETHYLPYRAZINE IN RATS

Abstract

It has been known that nicotinic acid (NA) binds to G protein-coupled receptor, GPR109A or HM74, on adipocytes, resulting in decreasing plasma non-esterified fatty acid (NEFA). A drawback of lipid-lowering therapy by NA comes from a rebound phenomenon found in plasma NEFA concentration. The compound 2,5-dimethylpyrazine (2,5-DMP), one of the Maillard reaction products, is known to be metabolized in the liver to 5-methylpyrazinoic acid, which binds to GPR109A as well as NA. We have previously reported that 2,5-DMP has an NEFA-lowering effect in rats. Here, we compare the effect of 2,5-DMP with those of NA on the blood concentration of NEFA. The most characteristic feature of NA was found in the rebound phenomenon that was not observed in 2,5-DMP. Co-administration of 2,5-DMP with NA did not show the rebound, resulting in continuous low concentrations of plasma NEFA. PRACTICAL APPLICATIONS In this study, we compared the non-esterified fatty acid (NEFA)-lowering effects of 2,5-dimethylpyrazine (2,5-DMP) and nicotinic acid (NA), which is found in roasted coffee. Administration of NA to rats induced the “NEFA rebound” while 2,5-DMP did not. Furthermore, co-administration of 2,5-DMP with NA did not result in the “NEFA rebound,” giving continuous low concentrations of plasma NEFA. Although the amount of 2,5-DMP in coffee is very low, many kinds of Maillard reaction products such as 2,5-DMP are found in roasted coffee. We also reported that some Maillard reaction products have NEFA-lowering effects. Therefore, we suggest that 2,5-DMP and other Maillard reaction products may be useful to suppress the “NEFA rebound” induced by NA.