Liraglutide Exerts Protective Effects by Downregulation of PPARγ, ACSL1 and SREBP-1c in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis

利拉鲁肽通过下调 PPARγ、ACSL1 和 SREBP-1c 在非酒精性脂肪变性和药物性脂肪变性的 Huh7 细胞培养模型中发挥保护作用

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作者:Tea Omanovic Kolaric, Tomislav Kizivat, Vjera Mihaljevic, Milorad Zjalic, Ines Bilic-Curcic, Lucija Kuna, Robert Smolic, Aleksandar Vcev, George Y Wu, Martina Smolic

Background

With the aging of the population and polypharmacy encountered in the elderly, drug-induced steatosis (DIS) has become frequent cause of non-alcoholic steatosis (NAS). Indeed, NAS and DIS may co-exist, making the ability to distinguish between the entities ever more important. The

Conclusions

LIRA ameliorates hepatocyte steatosis in Huh7 cell culture models of NAS and DIS.

Methods

Huh7 cells were treated with oleic acid (OA), or amiodarone (AMD) to establish models of NAS and DIS, respectively. Cells were treated with LIRA and cell viability was assessed by MTT, lipid accumulation by Oil-Red-O staining and triglyceride assay, and intracellular signals involved in hepatosteatosis were quantitated by RT-PCR. (3)

Results

After exposure to various OA and AMD concentrations, those that achieved 80% of cells viabilities were used in further experiments to establish NAS and DIS models using 0.5 mM OA and 20 µM AMD, respectively. In both models, LIRA increased cell viability (p < 0.01). Lipid accumulation was increased in both models, with microsteatotic pattern in DIS, and macrosteatotic pattern in NAS which corresponds to greater triglyceride accumulation in latter. LIRA ameliorated these changes (p < 0.001), and downregulated expression of lipogenic ACSL1, PPARγ, and SREBP-1c pathways in the liver (p < 0.01) (4) Conclusions: LIRA ameliorates hepatocyte steatosis in Huh7 cell culture models of NAS and DIS.

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