Tilorone attenuates high-fat diet-induced hepatic steatosis by enhancing BMP9-Smad1/5/8 signaling
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing and is caused by excessive fat deposition in the liver due to non-alcoholic factors. Aging is a major risk factor for the development and progression of MASLD. In this study, we investigated the...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2025
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| Sorozat: | GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)
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| Tárgyszavak: | |
| doi: | 10.1007/s11357-025-01685-8 |
| mtmt: | 36167268 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/39154 |
| Tartalmi kivonat: | The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing and is caused by excessive fat deposition in the liver due to non-alcoholic factors. Aging is a major risk factor for the development and progression of MASLD. In this study, we investigated the metabolic effects of tilorone, a synthetic small molecule, in a high-fat diet (HFD) mouse model, with a focus on the liver function and signaling. We demonstrate that tilorone attenuated HFD-induced steatosis by restoring bone morphogenetic protein 9 (BMP9)-Smad1/5/8 signaling and upregulating peroxisome proliferator-activated receptor gamma (PPARγ) expression. Tilorone reduced HFD-induced increases in body weight, adipose tissue and liver weight, and blood glucose levels, and improved glucose tolerance in HFD mice. PET/MRI imaging demonstrated enhanced 18 FDG ( 18 F-fluoro-2-deoxyglucose) uptake in liver, skeletal muscle, adipose tissue, and myocardium of tilorone-treated HFD animals. Histological analysis showed that tilorone reduced the HFD-induced diffuse, macrovesicular steatosis (S3/3), and machine learning-based image analysis revealed a decrease in lipid droplet size and lipid content. HFD caused the disappearance of liver glycogen, but tilorone increased glycogen levels. High-resolution respirometry indicated that tilorone reduced HFD-induced increases in mitochondrial complex II-linked oxidative phosphorylation and complex IV activity. These findings revealed the beneficial effects of tilorone on HFD and highlight its therapeutic potential in MASLD, particularly given that tilorone is a synthetic small molecule and can be administered orally. Further studies are required to explore its clinical application. |
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| Terjedelem/Fizikai jellemzők: | 18 |
| ISSN: | 2509-2715 |