Macrophages in obesity and non-alcoholic fatty liver disease: Crosstalk with metabolism

JHEP Reports : Innovation in Hepatology
Sander Lefere, Frank Tacke

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and a major cause of liver cirrhosis and hepatocellular carcinoma. NAFLD is intimately linked with other metabolic disorders characterized by insulin resistance. Metabolic diseases are driven by chronic inflammatory processes, in which macrophages perform essential roles. The polarization status of macrophages is itself influenced by metabolic stimuli such as fatty acids, which in turn affect the progression of metabolic dysfunction at multiple disease stages and in various tissues. For instance, adipose tissue macrophages respond to obesity, adipocyte stress and dietary factors by a specific metabolic and inflammatory programme that stimulates disease progression locally and in the liver. Kupffer cells and monocyte-derived macrophages represent ontologically distinct hepatic macrophage populations that perform a range of metabolic functions. These macrophages integrate signals from the gut-liver axis (related to dysbiosis, reduced intestinal barrier integrity, endotoxemia), from overnutrition, from systemic low-grade inflammation and from the local environment of a steatotic liver. This makes them central players in the progression of NAFL...Continue Reading

Citations

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Methods Mentioned

BETA
single-cell sequencing

Clinical Trials Mentioned

NCT03028740
NCT03053050
NCT03053063
NCT02686762
NCT03205345
NCT02960204
NCT02462967
NCT02316717
NCT02442687
NCT03676231

Software Mentioned

CENTAUR

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