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

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Abstract / Description of output

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]. 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], highlighted by the increased rates of cardiovascular disease in patients with MASLD [3] . 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.

Obesity is usually correlated with MASLD development and adipose tissue has been shown to respond to its inability to store the surplus of nutrients with the systemic release of lipids, cytokines and extracellular vesicles which in turn promote inflammation and fibrosis in distant organs [4]. This has been extensively demonstrated in mouse models of lipodystrophy where the redirection of lipids to the liver leads to the development of MASLD [4–6]. However, whether changes in adipose tissue occur in human MASLD, and how these might regulate disease initiation and propagation remain largely unknown (Figure 1). In this issue of the Journal of Hepatology, a study by Boesch and colleagues [7] provide insights into the association between human adipose-tissue macrophage (ATM) dysfunction and liver MASLD phenotype, proposing a novel mechanism through which aberrant macrophage differentiation and function in the adipose tissue can result in disruption of vascular barrier integrity and potentially contribute to enhanced inflammatory signalling between the adipose tissue and the liver in patients with MASH.
Original languageEnglish
Pages (from-to)390-393
Number of pages4
JournalJournal of Hepatology
Volume80
Issue number3
Early online date18 Dec 2023
DOIs
Publication statusPublished - Mar 2024

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