Left untreated, nonalcoholic fatty liver disease can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and end-stage liver disease. To date, few if any therapies have proven effective against NASH with fibrosis. Quantification and qualification of hepatic scar might enable development of more effective targeted therapies. In a murine model of NASH induced by diet, we characterized fibrillar collagen deposition within the hepatic parenchyma. At harvest, livers from the modified diet cohort exhibited NASH with fibrosis. Transcriptomic analysis of hepatic tissue revealed increased and each of which correlated directly with hepatic hydroxyproline content. Circular polarized microscopic analysis of Picrosirius red-stained liver sections revealed deposition of collagen type I within the parenchyma. Development of therapeutics designed to mitigate collagen type I accumulation might prove effective in NASH with fibrosis.
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http://dx.doi.org/10.3390/molecules26113316 | DOI Listing |
World J Gastroenterol
December 2024
Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India.
The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated at 32.4%, reflecting its growing clinical significance. MASLD, which includes MASLD and metabolic dysfunction-associated steatohepatitis (MASH) has been linked to increased metabolic, cardiovascular, and malignant morbidity.
View Article and Find Full Text PDFCureus
November 2024
Gastroenterology, University of Rochester, Rochester, USA.
Resmetirom is a thyroid hormone receptor agonist that has been recently approved by the FDA for the management of metabolic dysfunction-associated steatohepatitis (MASH). MASH is a severe form of metabolic dysfunction-associated fatty liver disease (MASLD), which is marked by hepatic inflammation and potential progression to cirrhosis and liver cancer. This review analyzes and demonstrates the efficacy of resmetirom in reducing intra-hepatic lipids, improving liver histology, and improving metabolic parameters.
View Article and Find Full Text PDFJ Gastrointestin Liver Dis
December 2024
Department of Gastroenterology, Gulhane School of Medicine, Ankara, Turkey.
Background And Aims: Insulin resistance is considered the most important key mechanism in the development of nonalcoholic fatty liver disease (NAFLD). Some studies have reported that hyperinsulinemia decreases the hepatic secretion of apolipoprotein (Apo) B. Chronic hyperinsulinemia in NAFLD may be responsible for the accumulation of triglycerides in hepatocytes.
View Article and Find Full Text PDFAnimal Model Exp Med
December 2024
GemPharmatech Chengdu Co., Ltd., Chengdu, China.
Background: The emerging incidence of pathogenic liver conditions is turning into a major concern for global health. Induction of pyroptosis in hepatocytes instigates cellular disintegration, which in turn liberates substantial quantities of pro-inflammatory intracellular substances, thereby accelerating the advancement of liver fibrosis. Consequently, directing therapeutic efforts towards inhibiting pyroptosis could potentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.
View Article and Find Full Text PDFDiseases
December 2024
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-9510, Japan.
Metabolic dysfunction-associated steatotic liver disease (MASLD) causes cellular senescence due to oxidative stress, endoplasmic reticulum stress, and ectopic fat deposition in the liver. Recently, dasatinib, an antitumor agent, and quercetin, a dietary supplement, were combined as a senolytic drug to eliminate senescent cells. Thus, this study aimed to examine the effects of dasatinib and quercetin administration on removing senescent cells and their therapeutic effects on MASLD in a medaka MASLD model.
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