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.
Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, Daejon.
Mi Yeon
MY
Chung
Mun-Chual
MC
Rho
Seung Woong
SW
Lee
Hye Ran
HR
Park
Koanhoi
K
Kim
In Ah
IA
Lee
Dong Hyun
DH
Kim
Kyung Hee
KH
Jeune
Hyun Sun
HS
Lee
Young Kook
YK
Kim
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