Honokiol activates the LKB1-AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes
| Autor: | Jung Hwan Kim, Min Suk Seo, Ki Churl Chang, Sang Won Park, Hye Jung Kim |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Honokiol
Male medicine.medical_specialty Pharmacology AMP-Activated Protein Kinases Fatty Acids Nonesterified Protein Serine-Threonine Kinases Toxicology Diet High-Fat Lignans chemistry.chemical_compound Mice Internal medicine Cell Line Tumor medicine Animals Humans Phosphorylation Protein kinase A Triglycerides biology Kinase Lipogenesis Biphenyl Compounds AMPK Hep G2 Cells Lipid Metabolism Mice Inbred C57BL Fatty acid synthase Endocrinology chemistry Liver biology.protein Hepatocytes Signal transduction Fatty Acid Synthases Sterol Regulatory Element Binding Protein 1 Stearoyl-CoA Desaturase Acetyl-CoA Carboxylase Signal Transduction |
| Zdroj: | Toxicology and applied pharmacology. 284(2) |
| ISSN: | 1096-0333 |
| Popis: | Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1h, and then exposed to 1mM free fatty acid (FFA) for 24h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28days, and honokiol (10mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated protein kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1-AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. |
| Databáze: | OpenAIRE |
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