Regulation of lipoprotein lipase expression by effect of hawthorn flavonoids on peroxisome proliferator response element pathway.
To investigate the possibility that natural medicines affect lipid metabolism by regulating lipoprotein lipase (LPL) expression, a green fluorescent protein (GFP) gene was constructed downstream of the peroxisome proliferator response element (PPRE) and the constructed plasmid was microinjected into Xenopus oocytes to establish a PPRE regulatory reporter system. Using this system, hawthorn flavonoids were quickly selected from a panel of natural medicines and found to up-regulate GFP expression by an effect on PPRE. To confirm the effect of hawthorn flavonoids, we treated mice orally with water (control), hawthorn flavonoids, and pioglitazone and measured the LPL levels in serum, adipose tissue, and muscle by an enzyme-linked immunosorbent assay. The serum LPL levels were no different from the controls after treatment with either hawthorn flavonoids or pioglitazone, but LPL increased significantly in muscular tissues and decreased in adipose tissues. These results demonstrate that hawthorn flavonoids meditate LPL expression in mice with tissue-specific differences. A novel PPRE regulatory report system was established for rapid and effective selection and evaluation of LPL-mediating drugs.
Fan
Chunlei
C
Life Science Department, Zhejiang College of Traditional Chinese Medicine, Hangzhou, China. snow@zjtcm.net
Yan
Jin
J
Qian
Ying
Y
Wo
Xingde
X
Gao
Liping
L
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology; D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D027825:Crataegus / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D009865:Oocytes; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D018515:Plant Leaves; D020218:Response Elements / Q000187:drug effects* / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014982:Xenopus laevis
D005419:Flavonoids; D047495:PPAR gamma; D045162:Thiazolidinediones; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D008071:Lipoprotein Lipase; D000077205:Pioglitazone