Novel Potential Drugs Identification for Liver Lipid Metabolism Modulation by High Content Screening
Date Issued
2015
Date
2015
Author(s)
Cheng, Ting-Yu
Abstract
Obesity, a common health condition, is also associated with many clinical disease including diabetes, cardiovascular disease and metabolic syndrome. The occurrence may be due to changes in lifestyle introduced in the 21st century which comprise increased consumption of energy dense foods and reduced physical activity. In addition, obesity plays an important role in other disease progression such as hepatocellular carcinoma (HCC) (risk by up to 4.5-fold), colorectal cancer, breast cancer, esophagus cancer, kidney cancer, pancreatic cancer and leukemia. Therefore drugs or diet supplements for metabolic modulation especially lipid biosynthesis may provide a disease prevention or a therapeutic strategy. In order to develop potential novel drug for this issue, we combined high content screening system, LOPAC1280(Library of Pharmacologically Active Compounds) and high fat medium culture system to screening potential drugs which can significantly modulate lipid metabolism or reduce the accumulation of cellular lipid droplets. Up to date, we have already finished screening all of drug library. We found SK-hep1 cells treated with high fat medium exhibited around 51.8±18.7 lipid droplets per cell compared to normal growth medium treatment (8.9±3.5 lipid droplets per cell). Among 1284 screened drug compounds, about 2.3% of them could effectively decrease more than 50% lipid droplet number compared with cells without drug treatment. We further identified 5 compounds that could reduce the accumulation of intracellular lipid droplets by utilizing mice primary hepatocyte culture system. These compounds also showed no cytotoxicity to hepatocyte in MTT assay. In the furture, these drugs need to be further investigated by experimental animal model as well as the underlying mechanism. The drug candidates may not only have benefits for liver protection but also provide a strategy for fatty liver prevention and therapy in health management.
Subjects
Obesity
Nonalcoholic Fatty Liver Disease
High content screening
SDGs
Type
thesis
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