Adipose tissue macrophage dysfunction in human MASLD – Cause or consequence?

Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), represents a huge global disease burden affecting a staggering 32.4% of the world's population [ [1] Riazi K. Azhari H. Charette J.H. Underwood F.E. King J.A. Afshar E.E. et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022; 7: 851-861https://doi.org/10.1016/S2468-1253(22)00165-0 Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar ]. Metabolic dysfunction-associated steatohepatitis (MASH), the more severe form of MASLD, is characterised by hepatic inflammation and fibrosis which can ultimately progress to cirrhosis and hepatocellular carcinoma. There remain no currently licensed disease-modifying therapies for the hepatic manifestations of MASH, with liver transplantation the only option for patients with advanced disease. Thus, a more detailed understanding of the cellular and molecular drivers of MASH pathogenesis are essential to identify novel therapeutic targets. Crucially, MASH is increasingly recognised as part of a systemic inflammatory disorder associated with obesity and metabolic syndrome [ [2] Byrne C.D. Targher G. NAFLD: A multisystem disease. J Hepatol. 2015; 62: S47-64https://doi.org/10.1016/j.jhep.2014.12.012 Abstract Full Text Full Text PDF PubMed Scopus (1866) Google Scholar ], highlighted by the increased rates of cardiovascular disease in patients with MASLD [ [3] Targher G. Byrne C.D. Tilg H. NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut. 2020; 69: 1691https://doi.org/10.1136/gutjnl-2020-320622 Crossref PubMed Scopus (311) Google Scholar ] . Hence, modulating the hepatic manifestations of the disease could have beneficial effects in the liver and beyond, whilst targeting inflammation in distant organs could potentially reduce the hepatic disease burden. However, an understanding of how changes in the diseased liver are linked to changes in other tissues and how this might regulate disease pathogenesis remains uncertain. Adipose tissue macrophage dysfunction is associated with a breach of vascular integrity in NASHJournal of HepatologyPreviewNon-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions, fueled by the obesity pandemic. In NAFLD, monocytes infiltrate visceral adipose tissue that promote local and hepatic inflammation. It however remains unclear what drives inflammation and how the immune landscape in adipose tissue differs across the NAFLD severity spectrum. We aimed to assimilate the adipose tissue macrophage (ATM) heterogeneity in a NAFLD cohort. Full-Text PDF Open Access