2019Chin J Diabetes MellitusRequires access

Effect of glucagon-like peptide-1 on lipid metabolism in hepatocytes by modification of forkhead box protein O1 phosphorylation sites

Ling Li, Xiaofeng Wang, Lanyu Zhang, M. Zha, Zhaohua Zhu, Dajin Zou

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Abstract

Objective To investigate whether glucagon-like peptide-1 (GLP-1) can regulate lipid metabolism in hepatocytes by modifying forkhead box protein O1 (FoxO1) phosphorylation sites. Methods The hepatic carcinoma cell line HepG2 cells were used to construct the hepatic steatosis model. Measuring the change of intracellular triglyceride (TG) of the GLP-1 treated cells fatty liver model, Western blot was used to detect changes in phosphorylation of Thr24, Ser256, and Ser319 in FoxO1; construction and transfection of the FoxO1-Ser256 mutant plasmid, RT-PCR was used to detect the changes of ACC and Fasn genes regulated by FoxO1. Results Compared with model group, ACC and Fasn mRNA level were lower than in GLP-1 treated model group, the difference was statistically significant (1.33±0.30 vs 4.21±0.66, 1.41±0.48 vs 3.05±0.67, t=5.31,4.16, all P 0.05). Conclusions GLP-1 may affect the expression of Foxol downstream gene ACC andFasn by modifying the phosphorylation sites of FoxO1, and reduce lipid formation in the fatty liver cell model. Key words: Non-alcoholic fatty liver disease; Glucagon-like peptide; Forkhead box protein O1; Phosphorylation

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Objective To investigate whether glucagon-like peptide-1 (GLP-1) can regulate lipid metabolism in hepatocytes by modifying forkhead box protein O1 (FoxO1) phosphorylation sites. Methods The hepatic carcinoma cell line HepG2 cells were used to construct the hepatic steatosis model. Measuring the change of intracellular triglyceride (TG) of the GLP-1 treated cells fatty liver model, Western blot was used to detect changes in phosphorylation of Thr24, Ser256, and Ser319 in FoxO1; construction and transfection of the FoxO1-Ser256 mutant plasmid, RT-PCR was used to detect the changes of ACC and Fasn genes regulated by FoxO1. Results Compared with model group, ACC and Fasn mRNA level were lower than in GLP-1 treated model group, the difference was statistically significant (1.33±0.30 vs 4.21±0.66, 1.41±0.48 vs 3.05±0.67, t=5.31,4.16, all P 0.05). Conclusions GLP-1 may affect the expression of Foxol downstream gene ACC andFasn by modifying the phosphorylation sites of FoxO1, and reduce lipid formation in the fatty liver cell model. Key words: Non-alcoholic fatty liver disease; Glucagon-like peptide; Forkhead box protein O1; Phosphorylation

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Available abstract

Objective To investigate whether glucagon-like peptide-1 (GLP-1) can regulate lipid metabolism in hepatocytes by modifying forkhead box protein O1 (FoxO1) phosphorylation sites. Methods The hepatic carcinoma cell line HepG2 cells were used to construct the hepatic steatosis model. Measuring the change of intracellular triglyceride (TG) of the GLP-1 treated cells fatty liver model, Western blot was used to detect changes in phosphorylation of Thr24, Ser256, and Ser319 in FoxO1; construction and transfection of the FoxO1-Ser256 mutant plasmid, RT-PCR was used to detect the changes of ACC and Fasn genes regulated by FoxO1. Results Compared with model group, ACC and Fasn mRNA level were lower than in GLP-1 treated model group, the difference was statistically significant (1.33±0.30 vs 4.21±0.66, 1.41±0.48 vs 3.05±0.67, t=5.31,4.16, all P 0.05). Conclusions GLP-1 may affect the expression of Foxol downstream gene ACC andFasn by modifying the phosphorylation sites of FoxO1, and reduce lipid formation in the fatty liver cell model. Key words: Non-alcoholic fatty liver disease; Glucagon-like peptide; Forkhead box protein O1; Phosphorylation

Key concepts: FOXO1, Phosphorylation, Steatosis, Glucagon, Lipid metabolism, FOXA2, Internal medicine, Endocrinology

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