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.

Alkylpyrazines from Coffee are Extensively Metabolized to Pyrazine Carboxylic Acids in the Human Body

“…A highly significant inhibition of phosphodiesterase activity was found, demonstrating that roasting‐associated compounds such as pyrazines can modulate platelet phosphodiesterase activity and cAMP concentrations in humans, which may contribute to the putative beneficial health effects of coffee . Furthermore, 2,5‐DMeP treatment reduced plasma levels of nonesterified fatty acids in rats; this was attributed to a presumed interaction between the corresponding carboxylic acid metabolite and the G‐protein coupled receptor GPR109A . Activation of this receptor by pyrazine‐2‐carboxylic acid (PA) was approximately 20‐fold less than by nicotinic acid …”