Abstract
In the present study, the molecular mechanisms by which CM108, a flavone derivative, improves lipid profiles were investigated further. Hyperlipidaemia was induced by oral administration of high cholesterol and fat. After 4 weeks of treatment, the lipid levels in the serum, liver and faeces were measured and the liver genes involved in lipid metabolism were analysed to explore the molecular mechanisms of lowering lipids. CM108 modulated lipid profiles, including elevating the level of high-density lipoprotein cholesterol (HDL-C; 40%) and reducing serum levels of triglyceride (10%), total cholesterol (10%) and low-density lipoprotein cholesterol (26%). Levels of triglyceride and total cholesterol in the liver were reduced by 18% and 24%, respectively. Increased HDL-C level was attributed to the synergic effects of CM108 in increasing levels of ATP-binding cassette transporter (ABC)A1, apolipoprotein AI and apolipoprotein AII in the liver. Intriguingly, CM108 induced genes, including fatty acid transport protein, acyl-CoA synthetase and lipoprotein lipase that are important for more efficient fatty acid beta-oxidation, thereby reducing serum and liver triglyceride levels. In addition, induction of ABCG5, ABCG8 and cholesterol 7al...Continue Reading
References
Feb 1, 1986·Journal of Nutritional Science and Vitaminology·T TokunagaN Hosoya
Jun 1, 1981·Digestive Diseases and Sciences·L CapocacciaM Angelico
Aug 18, 1995·The Journal of Biological Chemistry·K SchoonjansJ Auwerx
Nov 4, 1994·Cell·J E Schaffer, H F Lodish
Feb 7, 1997·The Journal of Biological Chemistry·J M LehmannT M Willson
Nov 14, 1997·The Journal of Biological Chemistry·G MartinJ Auwerx
Oct 27, 1998·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·K NagaoK Imaizumi
Dec 23, 1998·Atherosclerosis·F RinningerH Greten
Nov 23, 2000·Genes & Development·J J RepaD J Mangelsdorf
Nov 23, 2000·Genes & Development·J R SchultzB Shan
Dec 26, 2001·The Journal of Biological Chemistry·Martin MerkelHeiner Greten
May 3, 2002·Journal of Medicinal Chemistry·Jon L CollinsTimothy M Willson
May 8, 2002·The Journal of Clinical Investigation·Jay D HortonMichael S Brown
Jul 5, 2002·The Journal of Biological Chemistry·Aldo GrefhorstFolkert Kuipers
Sep 5, 2002·The Journal of Clinical Investigation·Gregory A GrafHelen H Hobbs
Nov 2, 2002·Nature Medicine·Joyce J Repa, David J Mangelsdorf
Apr 4, 2003·Journal of Medicinal Chemistry·Søren EbdrupPer Sauerberg
Sep 13, 2003·British Journal of Pharmacology·Ranjan ChakrabartiRamanujam Rajagopalan
Feb 13, 2004·The Journal of Pharmacology and Experimental Therapeutics·Thomas P BeyerGuoqing Cao
May 18, 2004·Journal of Lipid Research·Bowman MiaoRanjan Mukherjee
Oct 23, 2004·Pharmaceutical Research·Daniel H van RaalteKishor M Wasan
Oct 10, 2006·European Journal of Pharmacology·Lei GuoBang-Qiang Gong
Citations
Nov 21, 2013·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xiao-Hua YuChao-Ke Tang
Nov 1, 2012·Asian-Australasian Journal of Animal Sciences·J H ChoI H Kim
Jun 13, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Martin PorubaRostislav Vecera
Apr 4, 2017·Journal of Nutritional Science and Vitaminology·Ji Soo OhNamsoo Chang