RT Journal Article
SR Electronic
T1 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1317
OP 1327
DO 10.1136/gutjnl-2016-313654
VO 67
IS 7
A1 Mitchell Bijnen
A1 Tatjana Josefs
A1 Ilona Cuijpers
A1 Constantijn J Maalsen
A1 José van de Gaar
A1 Maria Vroomen
A1 Erwin Wijnands
A1 Sander S Rensen
A1 Jan Willem M Greve
A1 Marten H Hofker
A1 Erik A L Biessen
A1 Coen D A Stehouwer
A1 Casper G Schalkwijk
A1 Kristiaan Wouters
YR 2018
UL http://gut.bmj.com/content/67/7/1317.abstract
AB Objective Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c+ proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development.Design vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr-/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH.Results Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c+ and CD11c− macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c+ ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes.Conclusion ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.