Inhibition of Diacylglycerol Acyltransferase by Betulinic Acid from Alnus hirsuta

Abstract

During the screening for diacylglycerol acyltransferase (DGAT) inhibitors from natural products, the lupane-type triterpenoid betulinic acid was isolated from the methanol extract of Alnus hirsuta. It potently inhibited DGAT in the rat liver microsomes with an IC₅₀ value of 9.6 μM. Enzyme kinetic studies showed apparent Km and Ki values of 13.3 μM and 8.1 μM using [¹⁴ C]oleoyl-CoA as a substrate. A decrease in the apparent Vmax was observed with betulinic acid, whereas the apparent Km remained constant. Therefore, a Lineweaver-Burk plot of DGAT inhibition by betulinic acid showed a non-competitive type of inhibition. In the cell-based assay, betulinic acid inhibited triglyceride (TG) formation by human HepG2 cells. These findings suggest that betulinic acid may be a potential lead compound in the treatment of obesity.

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