Cells; co-auth.: W. Wahli

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Peroxisome Proliferator-Activated Receptor β/δ: A Link Between Metabolism, Inflammation, and Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease

Xavier Palomer  1   2   3   4 , Jue-Rui Wang  1   2   3   4 , Xiaoman Tang  1   2   3   4 , Siyuan Wu  1   2   3   4 , Ricardo Rodríguez-Calvo  3   5   6   7 , Walter Wahli  8   9 , Manuel Vázquez-Carrera  1   2   3   4

Affiliations

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered a hepatic manifestation of insulin resistance and ranges from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH). Hepatocyte ballooning, indicative of hepato-cellular damage, and liver inflammation, with or without fibrosis, are characteristic of MASH. Evidence shows that peroxisome proliferator-activated receptor β/δ (PPARβ/δ), expressed in the major liver cells (hepatocytes, Kupffer cells, cholangiocytes, and hepatic stellate cells), may help prevent the progression of MASLD by ameliorating insulin resistance, lipotoxicity, inflammation, and fibrosis. In this review, we summarize the molecular mechanisms by which PPARβ/δ attenuates the progression of MASLD and discuss future research perspectives.