title: The role of macrophages in obesity-driven chronic liver disease.
abstract: Overnutrition and a sedentary lifestyle have resulted in the expansion of human obesity and associated metabolic complications. Nonalcoholic fatty liver disease has become the most common chronic liver disease in Western developed countries and can range from simple hepatic steatosis to a combination of steatosis, inflammation, and ballooning degeneration (nonalcoholic steatohepatitis). Obesity and its related liver disease are both risk factors for hepatocellular carcinoma, the incidence of which is expected to increase rapidly. The pathogenesis of nonalcoholic fatty liver disease and its progression to nonalcoholic steatohepatitis and hepatocellular carcinoma involve a deregulated lipid metabolism and a disruption of immune homeostasis and tissue integrity and are associated with a state of chronic inflammation. Macrophages are immune cells essential for maintenance of organ function and homeostasis but can also contribute to tissue damage and maintain a proinflammatory response. Their function depends on their origin, and tissue and can be converted based on local environmental cues. Resident liver macrophages, Kupffer cells, which function as sentinels, provide a first defense and are assisted by infiltrating monocytes in cases of hepatic insult. Until now, the contribution of tissue-residing and infiltrating macrophages to the onset and progression of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and hepatocellular carcinoma has been only partially unraveled. This review summarizes the current knowledge on the contribution of macrophage subsets to obesity-driven fatty liver disease and its complications and sheds light on still unexplored areas.
authors.affiliation: Department of Hepatology and Gastroenterology, Ghent University, Belgium lindsey.devisscher@ugent.be.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Devisscher
authors.affiliation: Department of Hepatology and Gastroenterology, Ghent University, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Verhelst
authors.affiliation: Department of Hepatology and Gastroenterology, Ghent University, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Colle
authors.affiliation: Department of Hepatology and Gastroenterology, Ghent University, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
authors.affiliation: Department of Hepatology and Gastroenterology, Ghent University, Belgium.
authors.forename: Anja
authors.initials: A
authors.lastname: Geerts
mesh_terms: D000818:Animals; D002908:Chronic Disease; D018450:Disease Progression; D006801:Humans; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D008954:Models, Biological; D009765:Obesity / Q000150:complications* / Q000473:pathology*
keywords: Kupffer cell; monocyte; nonalcoholic fatty liver disease; steatohepatitis