Antihypertensive And Lipid-lowering Drugs Show Efficacy Against Steatotic Liver Disease

Now, a University of Barcelona study published successful nan journal Pharmacological Research shows that pemafibrate and telmisartan, 2 narcotics already approved for different conditions, efficaciously trim fat accumulation successful laboratory animal models of metabolic liver disease. Furthermore, nan study suggests that this operation of narcotics whitethorn thief to trim some liver engagement and associated cardiovascular complications. These results unfastened nan doorway to nan improvement of safer and much effective treatments for this disease, for which existent therapeutic options are very limited.

​​​​​​​The study has been carried retired by a squad led by Marta Alegret, professor astatine nan UB's Faculty of Pharmacy and Food Sciences, nan Institute of Biomedicine of nan UB (IBUB) and nan CIBER Area for Physiopathology of Obesity and Nutrition (CIBEROBN). The study has been carried retired successful collaboration pinch researchers from nan Santa Creu one Sant Pau Hospital Research Institute, nan Hospital Clínic de Barcelona, nan CIBER Area for Cardiovascular Diseases (CIBERCV) and Uppsala University (Sweden).

So far, astir caller compounds studied for nan curen of metabolic dysfunction-associated steatotic liver illness (MASLD) — formerly known arsenic fatty liver disease — person grounded successful objective tests for respective reasons, including information concerns. In this context, nan supplier repurposing pinch a known and acceptable adverse effect floor plan successful humans is an attractive, safe and much cost-effective strategy. This therapeutic repositioning is of peculiar liking successful nan early, usually asymptomatic, stages of nan disease.

"We person focused connected these phases pinch nan purpose of preventing nan illness from progressing to much terrible stages. But for a supplier to beryllium utilized successful these early stages, it must person a bully information floor plan successful humans," explains Marta Alegret.

Specifically, researchers person analyzed nan repurposing imaginable against MASLD of nan azygous aliases mixed management of a lipid-lowering supplier (pemafibrate) and an antihypertensive (telmisartan), some marketed — nan erstwhile only successful Japan — for nan curen of pathologies related to cardiovascular risk: hyperlipidemia and hypertension, respectively. "Mortality from cardiovascular causes is important successful patients pinch MASLD, and often these patients besides person these 2 consequence factors together," Alegret stresses. Zebrafish larvae, an replacement exemplary for studying nan disease

To corroborate the efficacy of nan narcotics and research their system of action, nan researchers person applied them to a rat exemplary of nan illness and, subsequently, to a zebrafish larval model. "In caller years, zebrafish person emerged arsenic an absorbing replacement exemplary that facilitates nan study of nan pathophysiology of MASLD and nan information of treatments. These are simpler and cheaper models that let results to beryllium obtained much quickly and which, though they are not identical to humans, person a carbohydrate/lipid metabolism and liver physiology akin to those of mammals," says nan UB professor.

The results show that nan operation of nan 2 narcotics reverses nan fat accumulation successful nan liver induced by a fare precocious successful fat and fructose. In addition, successful nan rat model, nan mixed management of half a dose of pemafibrate and half a dose of telmisartan was recovered to beryllium arsenic effective arsenic a afloat dose of either supplier successful reducing fat accumulation. "Combination therapy pinch narcotics acting connected different pathogenic pathways whitethorn beryllium a amended strategy than monotherapy, acknowledgment to imaginable synergistic effects and reduced toxicity related to nan usage of little doses of each drug," Alegret points out.

The operation of these 2 narcotics would beryllium beneficial not only for liver disease, but besides because "it lowers humor unit and cholesterin levels, and each this would consequence successful a little cardiovascular risk," she stresses.

The study besides recovered that each supplier useful by different mechanisms and describes, for nan first time, nan cardinal domiciled of nan PCK1 macromolecule successful telmisartan-derived hepatic lipid lowering. "Telmisartan is simply a supplier that has been utilized successful different models of MASLD, but mostly successful much precocious stages of nan disease, and its beneficial effects person been attributed chiefly to anti-inflammatory and anti-fibrotic effects. But successful nan early stages of nan illness location is nary inflammation aliases fibrosis yet, only lipid accumulation," explains nan researcher.

Researchers person now recovered that nan magnitude of PCK1 macromolecule successful nan livers of MASLD animals was reduced and that curen pinch telmisartan restored its levels to normal. "This summation successful PCK1 diverts nan flux of metabolites from lipid synthesis to glucose synthesis. This summation successful glucose accumulation could beryllium antagonistic if nan glucose were exported and accumulated successful nan blood, arsenic it could lead to diabetes, but we person noticed that this is not nan case," says nan UB professor.

Source:

Journal reference:

Bentanachs, R., et al. (2025) Telmisartan Reverses Hepatic Steatosis via PCK1 Upregulation: A Novel PPAR-independent Mechanism successful Experimental Models of MASLD. Pharmacological Research. doi.org/10.1016/j.phrs.2025.107860.