Inhibition of diacylglycerol acyltransferase by betulinic acid from Alnus hirsuta.
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 IC (50) value of 9.6 microM. Enzyme kinetic studies showed apparent Km and Ki values of 13.3 microM and 8.1 microM 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.
Chung
Mi Yeon
MY
Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, Daejon.
Rho
Mun-Chual
MC
Lee
Seung Woong
SW
Park
Hye Ran
HR
Kim
Koanhoi
K
Lee
In Ah
IA
Kim
Dong Hyun
DH
Jeune
Kyung Hee
KH
Lee
Hyun Sun
HS
Kim
Young Kook
YK
D029661:Alnus; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D053978:Pentacyclic Triterpenes; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000094062:Betulinic Acid
D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; D051048:Diacylglycerol O-Acyltransferase; D000094062:Betulinic Acid