Wnt/beta‐catenin signaling and its modulators in nonalcoholic fatty liver diseases

• Published in: Hepatobiliary & pancreatic diseases international Vol. 22; no. 4; pp. 333 - 345
• Main Authors: Shree Harini, Karthik, Ezhilarasan, Devaraj
• Format: Journal Article
• Language: English
• Published: Singapore Elsevier B.V 01.08.2023; Department of Pharmacology,Molecular Medicine and Toxicology Lab,Saveetha Dental College,Saveetha Institute of Medical and Technical Sciences(SIMATS),Chennai,Tamil Nadu 600077,India
• Subjects: Chronic liver diseases; Fatty liver; Fibrosis; Oxidative stress; Steatosis; Wnt/β-catenin; Oxidative stress; Chronic liver diseases; Fatty liver; Wnt/β-catenin; Fibrosis; Steatosis
• ISSN: 1499-3872
• DOI: 10.1016/j.hbpd.2022.10.003

Nonalcoholic fatty liver disease (NAFLD) is a global health concern associated with significant morbidity and mortality. NAFLD is a spectrum of diseases originating from simple steatosis, progressing through nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis that may lead to hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is mediated by the triglyceride accumulation followed by proinflammatory cytokines expression leading to inflammation, oxidative stress, and mitochondrial dysfunction denoted as “two-hit hypothesis”, advancing with a “third hit” of insufficient hepatocyte proliferation, leading to the increase in hepatic progenitor cells contributing to fibrosis and HCC. Wnt/β-catenin signaling is responsible for normal liver development, regeneration, hepatic metabolic zonation, ammonia and drug detoxification, hepatobiliary development, etc., maintaining the overall liver homeostasis. The key regulators of canonical Wnt signaling such as LRP6, Wnt1, Wnt3a, β-catenin, GSK-3β, and APC are abnormally regulated in NAFLD. Many experimental studies have shown the aberrated Wnt/β-catenin signaling during the NAFLD progression and NASH to hepatic fibrosis and HCC. Therefore, in this review, we have emphasized the role of Wnt/β-catenin signaling and its modulators that can potentially aid in the inhibition of NAFLD.