Effects of Fibrates and Chemicals on Lipoprotein Lipase Expression
Date Issued
2009
Date
2009
Author(s)
Chen, Chia-Jung
Abstract
Lipoprotein lipase ( LPL ) gene located at human chromosome 8. The human LPL gene is now known to comprise 10 exons and 9 introns spanning approximately 30 kb. LPL are synthesized in many tissues, such as adipose tissue, skeletal muscle, brain and kidney,etc. The synthesized LPL then being secreted to capillary, binding with HSPG which is on cell surface so that it can attatch to capillary wall. Lipoprotein lipase plays an important role in the metabolism of plasma lipid metabolism. It catalyzes the hydrolysis of triglycerides from chylomicrons and very low density lipoprotein into glycerol, diacylglycerol and free fatty acids and the free fatty acids are supplied to tissues as sources of metabolic energy or stored as triglycerides after re-esterification. The defect in LPL gene can cause type I hyperlipoproteinemia and affect lipid homeostasis, symptoms like high triglyceride, accompany with recurrent abdominal pain, hepatosplenomegaly, pancreatitis,etc are found in clinical patients. The drugs performed so far are fibrates, which enhance LPL expression by regulating peroxisome proliferator-activated receptors (PPAR). Additionally, there are also reports which show that curcumin and esculetin can lower cholesterol and triglyceride. In this research, we investigated effects of these drugs on LPL expression. Moreover, recent research about Sirtuin family also shows that SIR1 can regulate synthesis of glucose and insulin and adipose metabolism, etc. Resveratrol, the most potent molecule that enhances SIRT1 activity. Therefore whether resveratrol can enhance LPL synthesis and activity will be investigated.n previous report, we observed significant expression of reporter gene（β-galactosidase） （P<0.05） in drugs-treated cells transfected with plasmid carrying human LPL promoter. However, no LPL activity was expressed when report gene was replaced with LPL cDNA. The reason might be the lack of +80 ~ +144 sequence on 5''UTR. So we reconstructed a new plasmid (pLPLwt) which carried LPL promoter and cDNA region (includeing +80 ~ +144 sequence) to check whether LPL could be expressed in CHO-K1 cells and enhanced after treatment of drugs.The data shoewed that esculetin, resveratrol enhanced LPL expression up to about 1.2 ~3.5 fold compared with the control group. In addition to fibrates, however, no effect on LPL expression by curcumin was observed. We concluded that esculetin and resveratrol enhanced LPL expression on CHO-K1 cell. We hope that we can apply these drugs to mutant form LPL, furthermore apply theses drugs into clinical treatment.
Subjects
Lipoprotein lipase
Hyperlipoproteinemia
Resveratrol
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