Abstract
Nonalcoholic fatty liver disease (NAFLD) and its progressive inflammatory form, nonalcoholic
steatohepatitis (NASH), are leading causes of liver cirrhosis and hepatocellular carcinoma.
Metabolism and inflammation are intimately interrelated in NAFLD/NASH, as expressed
by the term immunometabolism. Hepatic macrophages mediate inflammatory responses during
metabolic disorders and can stimulate or dismantle liver fibrosis. Their functional
diversity is partly explained by heterogeneous macrophage subsets: tissue-resident
Kupffer cells and monocyte-derived macrophages. However, macrophages themselves are
altered in their functional polarization by dietary composition and metabolic or inflammatory
stimuli in NAFLD. The inflammatory polarization of macrophages correlates with changes
in core metabolism pathways like oxidative phosphorylation and glycolysis. The availability
of nutrients, such as glucose or fatty acids or oxygen also influences macrophage
polarization upon danger signal or cytokine reception. Understanding the interplay
of metabolism and macrophage function in NASH may open new approaches to therapeutic
targeting of these essential modifiers in metabolic liver diseases.
Keywords
metabolism - immunology - chemokine - steatosis - fibrosis
