Liraglutide reduces lipid accumulation in steatotic L‑02 cells by enhancing autophagy

Zhou,Shi‑Wei; Zhang,Man; Zhu,Min

doi:10.3892/mmr.2014.2569

Liraglutide reduces lipid accumulation in steatotic L‑02 cells by enhancing autophagy

Authors:
- Shi‑Wei Zhou
- Man Zhang
- Min Zhu
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Affiliations: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
Published online on: September 15, 2014 https://doi.org/10.3892/mmr.2014.2569
Pages: 2351-2357
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Simple hepatic steatosis is the early stage of non‑alcoholic fatty liver disease and is recognized as a benign process. Previous studies show that glucagon‑like peptide‑1 has great potential in improving hepatic steatosis. Recent data have revealed that inhibiting autophagy exacerbates lipid accumulation in hepatocytes. Therefore, the present study aimed to determine the effects of liraglutide (LG) on simple hepatic steatosis and the possible role of autophagy. Firstly, steatotic L‑02 cells were induced by incubating L‑02 cells with 1 mmol/l free fatty acid (FFA) mixture (oleic acid and palmitic acid at a molar ratio of 2:1) for 24 h. Intracellular lipid accumulation, cell viability, oxidative stress and apoptosis were evaluated. Secondly, steatotic L‑02 cells were treated with 10 or 100 nmol/l LG, 100 nmol/l LG plus 3‑methyladenine (3‑MA), or rapamycin for 24 h, and then lipid accumulation was measured. Next, the degree of lipid accumulation and the intensity of autophagy were assessed. Oil red O staining and triglyceride quantification demonstrated notable steatosis in L‑02 cells following exposure to 1 mmol/l FFA mixture for 24 h. There was no significant cytotoxicity, oxidative stress or apoptosis in steatotic L‑02 cells. Treatment with 100 nmol/l LG reduced lipid accumulation in steatotic L‑02 cells and increased the mRNA levels of microtubule‑associated protein 1 light chain 3B. Additionally, it enhanced the autophagic flux in steatotic L‑02 cells, as measured by western blot analysis and shown by electron microscopy. Additionally, 3‑MA weakened the ability of LG to improve hepatic steatosis and enhance autophagy. Our data indicate that LG reduces the lipid accumulation in steatotic L‑02 cells, and the activation of autophagy plays a significant role in this process.

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