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

Előnézet	Szöveg (Disszertáció) Download (2MB) | Előnézet
Előnézet	Szöveg (Tézisfüzet) Download (246kB) | Előnézet
Előnézet	Szöveg (Tézisfüzet) Download (294kB) | Előnézet
Előnézet	Szöveg (Kapcsolódó saját publikációk) Download (12MB) | Előnézet

Absztrakt (kivonat) idegen nyelven

Background and aims: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing, making it the most common liver disease worldwide nowadays. It is closely associated with different metabolic disorders such as obesity, diabetes, and cardiovascular diseases. Epidemiological projections indicate a continuous rise in global prevalence each year. Importantly, MASLD affects not only adult population, its incidence is also increasing among children and adolescents, further amplifying its impact as a major global health problem. MASLD is characterized by excessive accumulation of triglycerides in the liver that is not caused by alcohol consumption. The more severe form is marked by hepatocellular damage, which may subsequently progress to fibrosis and liver cancer. Type 2 diabetes mellitus (T2DM), characterized by relative insulin deficiency, obesity, and aging, represents the major risk factors for the development and progression of MASLD. Bone morphogenetic proteins (BMPs) play an important role in the development of MASLD. Previous studies have shown that BMPs reduced body weight, blood glucose levels, and the lipid content of the liver. Given the increasing prevalence of MASLD, the development of novel therapeutic strategies is urgently needed. Accordingly, our aim was to investigate the effect of the BMP-inducing agent tilorone on metabolism, with a particular focus on hepatic lipid accumulation in vivo. Materials and methods: Twelve- to fourteen-week-old male C57BL/6 mice were used in a 10-week experimental period. Mice were randomly divided into three groups: (1) control group; (2) high-fat diet (HFD) group were treated of intraperitoneal saline injections (25µl saline/kg body weight) every third day during weeks 3-10; and (3) HFD + tilorone group were treated of intraperitoneal tilorone injections (25mg tilorone/kg body weight) every third day during weeks 3-10. Body mass and blood glucose levels were measured weekly. Intraperitoneal glucose tolerance test was performed on the 9th week. At the end of the experimental period one set of animals also underwent PET/MRI imaging. After the 10 weeks experimental period the animals were euthanized and internal organs (heart, liver, kidney, abdominal fat) and the hindlimb muscles were isolated. High-resolution respirometry was performed on freshly isolated liver samples. Further investigation liver tissue samples were also embedded for histological analysis. One set of animals in each group was terminated after 6 weeks for histological analysis.

Tétel nézet