PloS one, 2016-12, Vol.11 (12), p.e0166913-e0166913
2016
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- Autor(en) / Beteiligte
- Titel
- Exendin-4 Inhibits Hepatic Lipogenesis by Increasing β-Catenin Signaling
- Ist Teil von
- PloS one, 2016-12, Vol.11 (12), p.e0166913-e0166913
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The aim of this study is to investigate whether the beneficial effect of exendin-4 on hepatic steatosis is mediated by β-catenin signaling. After the HepG2 human hepatoma cells were treated with PA for 24 hours, total triglycerides levels were increased in a dose-dependent manner, and the expression levels of perilipin family members were upregulated in cells treated with 400 μM PA. For our in vitro model of hepatic steatosis, HepG2 cells were treated with 400 μM palmitic acid (PA) in the presence or absence of 100 nM exendin-4 for 24 hours. PA increased the expression of lipogenic genes, such as sterol regulatory element-binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor gamma (PPARγ), stearoyl-CoA desaturase 1 (SCD1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and triglyceride synthesis-involved genes, such as diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2) in HepG2 cells, whereas exendin-4 treatment significantly prevented the upregulation of SREBP-1c, PPARγ, SCD1, FAS, ACC, DGAT1 and DGAT2. Moreover, exendin-4 treatment increased the expression of phosphorylated glycogen synthase kinase-3 beta (GSK-3β) in the cytosolic fraction and the expression of β-catenin and transcription factor 4 (TCF4) in the nuclear fraction. In addition, siRNA-mediated inhibition of β-catenin upregulated the expression of lipogenic transcription factors. The protective effects of exendin-4 on intracellular triglyceride content and total triglyceride levels were not observed in cells treated with the β-catenin inhibitor IWR-1. These data suggest that exendin-4 treatment improves hepatic steatosis by inhibiting lipogenesis via activation of Wnt/β-catenin signaling.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0166913Titel-ID: cdi_plos_journals_1845246732
- Format
- –
- Schlagworte
- Acetyl-CoA carboxylase, Acetyl-CoA Carboxylase - genetics, Acetyl-CoA Carboxylase - metabolism, Acyltransferase, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism, beta Catenin - agonists, beta Catenin - antagonists & inhibitors, beta Catenin - genetics, beta Catenin - metabolism, Biology and Life Sciences, Cell growth, Cell Nucleus - drug effects, Cell Nucleus - metabolism, Cytosol - drug effects, Cytosol - metabolism, Desaturase, Diabetes, Diacylglycerol, Diacylglycerol O-Acyltransferase - genetics, Diacylglycerol O-Acyltransferase - metabolism, Diglycerides, Fatty Acid Synthase, Type I - genetics, Fatty Acid Synthase, Type I - metabolism, Fatty acids, Fatty liver, Fatty-acid synthase, Gene expression, Gene Expression Regulation, Genes, Glycogen, Glycogen synthase kinase 3, Glycogen Synthase Kinase 3 beta - genetics, Glycogen Synthase Kinase 3 beta - metabolism, Hep G2 Cells, Hepatoma, Hospitals, Humans, Hypoglycemic Agents - pharmacology, Imides - pharmacology, Insulin resistance, Internal medicine, Lipogenesis, Lipogenesis - drug effects, Liver, Liver diseases, Medical research, Medicine, Medicine and Health Sciences, Metabolism, Musculoskeletal system, Palmitic acid, Palmitic Acid - antagonists & inhibitors, Palmitic Acid - pharmacology, Penicillin, Peptides - pharmacology, PPAR gamma - genetics, PPAR gamma - metabolism, Proteins, Quinolines - pharmacology, RNA, Small Interfering - genetics, RNA, Small Interfering - metabolism, Rodents, Signaling, siRNA, Stearoyl-CoA desaturase, Stearoyl-CoA Desaturase - genetics, Stearoyl-CoA Desaturase - metabolism, Steatosis, Sterol Regulatory Element Binding Protein 1 - genetics, Sterol Regulatory Element Binding Protein 1 - metabolism, Sterol regulatory element-binding protein, Sterol regulatory element-binding protein 1c, Sterols, Transcription Factor 4, Transcription factors, Transcription Factors - genetics, Transcription Factors - metabolism, Triglycerides, Venoms - pharmacology, Wnt protein, Wnt Signaling Pathway, β-Catenin