Tilorone attenuates high-fat diet-induced hepatic steatosis by enhancing BMP9-Smad1/5/8 signaling.

Barnabas Horvath, Judit Halasz, Norman Noel Tanner, Zoltan Marton Kohler, Gyorgy Trencsenyi, Laszlo Juhasz, Laszlo Rovo, Andras Kiss, Aniko Keller-Pinter

Department of Biochemistry, Albert Szent-Gyorgyi Medical School, Centre of Excellence for Interdisciplinary Research, Development and Innovation, University of Szeged, Szeged, Hungary.Department of Biochemistry, Albert Szent-Gyorgyi Medical School, Centre of Excellence for Interdisciplinary Research, Development and Innovation, University of Szeged, Szeged, Hungary. · pubmed

Paper

Abstract

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

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Research summary

Tilorone attenuates high-fat diet-induced hepatic steatosis by enhancing BMP9-Smad1/5/8 signaling. The study addresses metabolic dysfunction associated with aging, specifically focusing on liver health, which is a critical aspect of longevity research.

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