Metabolic Syndrome Ameliorated by 4-Methylesculetin by Reducing Hepatic Lipid Accumulation
| Autor: | Linghuan Li, Guangyao Zhu, Gaohang Fu, Weiwei Zha, Hanbing Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Metabolic Syndrome
NF-E2-Related Factor 2 Organic Chemistry General Medicine Diet High-Fat Lipids Catalysis visceral obesity hepatic steatosis 4-methylesculetin adipose microenvironment metabolic syndrome Computer Science Applications Fatty Liver Mice Inbred C57BL Inorganic Chemistry Mice Liver Animals PPAR alpha Obesity Umbelliferones Insulin Resistance Physical and Theoretical Chemistry Sterol Regulatory Element Binding Protein 1 Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 18; Pages: 10465 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms231810465 |
| Popis: | Obesity is a chronic metabolic disease caused by an imbalance between energy intake and expenditure during a long period and is characterized by adipose tissue disfunction and hepatic steatosis. The aim of this study was to investigate the effect of 4-methylesculetin (4-ME), a coumarin derivative, upon adipose microenvironment and hepatic steatosis in mice induced by a high-fat diet (HFD), and to explore potential mechanisms of its beneficial effect on metabolic disorders. HFD-fed mice displayed visceral obesity, insulin resistance, and hepatic lipid accumulation, which was remarkably ameliorated by 4-ME treatment. Meanwhile, 4-ME ameliorated adipocyte hypertrophy, macrophage infiltration, hypoxia, and fibrosis in epididymal adipose tissue, thus improving the adipose tissue microenvironment. Furthermore, 4-ME reversed the increase in CD36, PPAR-γ, SREBP-1, and FASN, and the decrease in CPT-1A, PPAR-α, and Nrf2 translocation into the nucleus in livers of HFD mice and in FFA-incubated hepatocytes. Moreover, the beneficial effects of 4-ME upon lipid deposition and the expression of proteins related to lipid metabolism in FFA-induced LO2 cells were abolished by ML385, a specific Nrf2 inhibitor, indicating that Nrf2 is necessary for 4-ME to reduce hepatic lipid deposition. These findings suggested that 4-ME might be a potential lead compound candidate for preventing obesity and MAFLD. |
| Databáze: | OpenAIRE |
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