Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding

Abstract

Chronic inflammation of adipose tissue in obesity is by now an established phenomenon, but the initiating event(s) of the inflammatory cascade are still unknown. We hypothesized that neutrophil infiltration into adipose tissue may precede macrophage infiltration as in classical immune responses. Here we demonstrate that early (3 and 7 days) after initiating high-fat feeding of C57BL/6J mice, neutrophils transiently infiltrate the parenchyma of intra-abdominal adipose tissue. Mean periepdidymal fat myeloperoxidase expression (representing neutrophils) and and 7 neutrophils and by in neutrophils of in by the in of of the of by neutrophils of of in of that the is by neutrophil and Chronic inflammation of adipose tissue in obesity is by now an established phenomenon, but the initiating event(s) of the inflammatory cascade are still unknown. We hypothesized that neutrophil infiltration into adipose tissue may precede macrophage infiltration as in classical immune responses. Here we demonstrate that early (3 and 7 days) after initiating high-fat feeding of C57BL/6J mice, neutrophils transiently infiltrate the parenchyma of intra-abdominal adipose tissue. Mean periepdidymal fat myeloperoxidase expression (representing neutrophils) and and 7 neutrophils and by in neutrophils of in by the in of of the of by neutrophils of of in of that the is by neutrophil and is as by inflammation inflammatory in adipose is by of inflammatory and and by an of of in adipose tissue. of in adipose and in and and in fat the tissue in in as an and as of inflammatory of the of adipose tissue in the are of as and and adipose tissue in obesity by of are of is macrophage in adipose inflammation in fat in the of now that infiltration of immune in the of that infiltration into adipose tissue in mice, and the of inflammatory and of high-fat macrophage infiltration into adipose and in the of macrophage infiltration into the fat in the and of infiltration of in adipose tissue is in infiltration into fat of and the of the in in and the of inflammatory and inflammatory of and adipose tissue may by immune and may the of obesity of adipose tissue infiltration by in the high-fat of macrophage infiltration of obesity is macrophage in adipose adipose tissue and obesity and inflammatory inflammatory infiltration of by infiltrate is by infiltration of the tissue by neutrophils and may the that in an established of adipose tissue may by immune of the and the that adipose tissue that neutrophils we hypothesized that neutrophil infiltration of adipose tissue may precede the macrophage we the that neutrophils transiently infiltrate adipose tissue as early as after initiating high-fat in We in that neutrophil and and and in the of neutrophils myeloperoxidase and and by and and the the of the and of C57BL/6J of high-fat as adipose tissue and obesity and and by and periepdidymal and fat in the and in and in an of 7 tissue and and into in as we of and in and the of by of by and of in of and by and by after of and of of and and the in neutrophils of and in neutrophils the and the the in of and in the by of the the in the as the of by neutrophils as the of by the as of of the of neutrophils the and in and as of by of of and as the expression of in neutrophils in in the the and by expression of in and the the and by and fat in and of and the the and adipose fat neutrophils by and of in and the the and the neutrophils in in and the of the and as of and in and in the of the as of the of in of and in of in the neutrophils and the in of the and and in of the of and the in in and the of the and the and by neutrophils as of in the of and by and into and the by the in in and of by in of the and fat in and by in of macrophage and in adipose tissue of and and in of in and of by in of by the the and in an of macrophage by the of are as of by of the neutrophils infiltrate adipose tissue macrophage we C57BL/6J mice, obesity high-fat high-fat an of in as early as after of high-fat feeding and high-fat mice, in of in adipose tissue the of adipose tissue we of adipose tissue the the neutrophil adipose tissue expression and and and and of adipose tissue expression of in is in Mean periepdidymal fat expression and and 7 and in expression in in expression in adipose tissue and high-fat and and neutrophils that that of adipose tissue the the of neutrophils the parenchyma of the adipose tissue in neutrophils by in adipose tissue neutrophils in fat of high-fat and 7 high-fat but established adipose tissue by as by macrophage and in adipose tissue of and and 7 and and the of expression that of in intra-abdominal fat of tissue demonstrate that neutrophils transiently infiltrate intra-abdominal adipose tissue early in the of by the infiltration of adipose tissue by infiltration of adipose tissue in of neutrophils by in fat and in high-fat (3 of high-fat are in the are of the after and 7 of high-fat feeding expression is in of fat high-fat high-fat neutrophils of as in the of we an in the of neutrophils the We the in neutrophils the of the in We by neutrophils of of the neutrophils the and of by the of neutrophils the the in the of neutrophils and in the of of the of in the we the of as the by and that neutrophil (3 in that of neutrophils the in the by the neutrophil neutrophil of by the of neutrophils the of neutrophils that of and an in the early after initiating high-fat feeding in that of neutrophils and the of neutrophils and the of neutrophils of of neutrophils by of by as in in the of are of of neutrophils and and the neutrophils and of neutrophils of of in the neutrophils in the in the of of neutrophils in the of the and neutrophils are the in neutrophil is by of by and we neutrophil in and of of in the of of by and and the of of neutrophils and in in the of the of that in the of the that the is the of neutrophil in the we of neutrophils the in the and the of neutrophils the of and the of neutrophils in neutrophils by and neutrophils the are of neutrophils in neutrophil by the neutrophil we the of and the an of the of by neutrophils the in the and in the of demonstrate that and are of the of the and are of by and by of neutrophils in the of the of are of in in is of the of is we the of the that is of in and in inflammation and We the the of neutrophils in and in the by neutrophils we demonstrate an and the and of by of and of the that of neutrophils the of the of in the and of the in of and in of neutrophils we that of the of by the the that the neutrophils and is by the and by neutrophils and neutrophil and expression of in in by of in are of neutrophils the are of neutrophils in of and and by and of by the of of are of obesity and the the adipose tissue of that fat is of the of obesity an in fat inflammation in fat in the of of of fat by of an of and the in intra-abdominal fat by of fat in of fat adipose tissue in obesity in the of fat the adipose tissue early in the of high-fat feeding of neutrophils transiently infiltrate the parenchyma of intra-abdominal adipose and in neutrophils in that is by and by the neutrophil but is of is by the of by neutrophil and that inflammatory is by inflammatory by neutrophils is in inflammation an the that adipose tissue in high-fat feeding the of adipose tissue inflammation in by the that the is in adipose tissue in obesity and of the in adipose tissue in obesity of inflammatory as of in adipose tissue. of in adipose in and and in fat and as as an as and inflammatory of and and the of the adipose tissue as an infiltration of into adipose tissue is macrophage in adipose and and in by inflammatory and and inflammatory of and that adipose tissue inflammation may inflammation and the the inflammatory cascade is in obesity unknown. are the demonstrate that high-fat feeding of neutrophils intra-abdominal tissue. inflammatory as an early high-fat and inflammatory infiltration into adipose tissue of infiltrate adipose tissue adipose tissue and obesity macrophage and in adipose tissue of and neutrophils are in adipose infiltration the of initiating high-fat feeding and adipose tissue and obesity neutrophil infiltration into adipose tissue is is neutrophil neutrophils of infiltration and and by adipose tissue in obesity of in adipose tissue. of in adipose may as as and and of the adipose that neutrophil are in the of adipose tissue in and inflammation in adipose inflammation by and in adipose tissue infiltration of neutrophils may that in high-fat feeding neutrophils are the adipose tissue infiltrate the parenchyma and are in in an of neutrophils is by neutrophil and of neutrophil an the of in the the of of the of neutrophils and and the of by and the of by neutrophils and of inflammatory infiltration into adipose tissue the of obesity is by the in of adipose tissue in the of adipose tissue and obesity and macrophage infiltration inflammatory and of high-fat the of macrophage infiltration into intra-abdominal adipose tissue infiltration of in adipose tissue is in and of infiltration of in adipose tissue is in infiltration into fat of and the of still the and adipose tissue in in the in adipose tissue inflammation and of infiltration of into adipose in adipose tissue and of in adipose and but adipose tissue inflammation is the of neutrophils are in that neutrophils in adipose tissue and of the and is of that of and into is the of an inflammatory but the of inflammatory as and in of neutrophils in the and of of and in the of the inflammatory cascade in inflammatory in of neutrophils in the and of of the of adipose tissue inflammation as neutrophil infiltration in initiating the inflammatory cascade in high-fat is as by inflammation inflammatory in adipose is by of inflammatory and and by an of of in adipose tissue. of in adipose and in and and in fat the tissue in in as an and as of inflammatory of the of adipose tissue in the are of as and and adipose tissue in obesity by of are of is macrophage in adipose inflammation in fat in the of now that infiltration of immune in the of that infiltration into adipose tissue in mice, and the of inflammatory and of high-fat macrophage infiltration into adipose and in the of macrophage infiltration into the fat in the and of infiltration of in adipose tissue is in infiltration into fat of and the of the in in and the of inflammatory and inflammatory of and adipose tissue may by immune and may the of obesity of adipose tissue infiltration by in the high-fat of macrophage infiltration of obesity is macrophage in adipose adipose tissue and obesity and inflammatory inflammatory infiltration of by infiltrate is by infiltration of the tissue by neutrophils and may the that in an established of adipose tissue may by immune of the and the that adipose tissue that neutrophils we hypothesized that neutrophil infiltration of adipose tissue may precede the macrophage we the that neutrophils transiently infiltrate adipose tissue as early as after initiating high-fat in We in that neutrophil and and and in the of neutrophils myeloperoxidase and and by and and the the of the and of C57BL/6J of high-fat as adipose tissue and obesity and and by and periepdidymal and fat in the and in and in an of 7 tissue and and into in as we of and in and the of by of by and of in of and by and by after of and of of and and the in neutrophils of and in neutrophils the and the the in of and in the by of the the in the as the of by neutrophils as the of by the as of of the of neutrophils the and in and as of by of of and as the expression of in neutrophils in in the the and by expression of in and the the and by and fat in and of and the the and adipose fat neutrophils by and of in and the the and the neutrophils in in and the of the and as of and in and in the of the as of the of in of and in of in the neutrophils and the in of the and and in of the of and the in in and the of the and the and by neutrophils as of in the of and by and into and the by the in in and of by in of the and fat in and by in of macrophage and in adipose tissue of and and in of in and of by in of by the the and in an of macrophage by the of are as of by of the and and in the of neutrophils myeloperoxidase and and in the of neutrophils myeloperoxidase and and by and and the the of the and of C57BL/6J of high-fat as adipose tissue and obesity and and by and periepdidymal and fat in the and in and in an of 7 tissue by and and the the of the and of C57BL/6J of high-fat as adipose tissue and obesity and and by and periepdidymal and fat in the and in and in an of 7 tissue and and into in as we of and in and the of by and into in as we of and in and the of by of by and of in of and by and by after of and of by and of in of and by and by after of and of of and and the in neutrophils of and in neutrophils the and the the in of and in the by of the the in the as the of of and and the in neutrophils of and in neutrophils the and the the in of and in the by of the the in the as the of by neutrophils as the of by the as of of the of neutrophils the and in and as of by of of and as the of by neutrophils as the of by the as of of the of neutrophils the and in and as of by of of and as the expression of in neutrophils in in the the and by neutrophils in in the the and by expression of in and the the and by and the the and by and fat in and of and the the and adipose fat neutrophils by and of in and the the and the neutrophils in in and the of the and as of and in and in the of the as of the of in of and in and fat in and of and the the and adipose fat neutrophils by and of in and the the and the neutrophils in in and the of the and as of and in and in the of the as of the of in of and in of in the neutrophils and the in of the and and in of the of and the in in and the of the and the the neutrophils and the in of the and and in of the of and the in in and the of the and the and by neutrophils as of in the of and by and into and the by the in in and of by in of the and fat in and by in of macrophage and in adipose tissue of and and in of in and of by in of by the the and in an of macrophage by the of by neutrophils as of in the of and by and into and the by the in in and of by in of the and fat in and by in of macrophage and in adipose tissue of and and in of in and of by in of by the the and in an of macrophage by the of are as of by of the are as of by of the neutrophils infiltrate adipose tissue macrophage we C57BL/6J mice, obesity high-fat high-fat an of in as early as after of high-fat feeding and high-fat mice, in of in adipose tissue the of adipose tissue we of adipose tissue the the neutrophil adipose tissue expression and and and and of adipose tissue expression of in is in Mean periepdidymal fat expression and and 7 and in expression in in expression in adipose tissue and high-fat and and neutrophils that that of adipose tissue the the of neutrophils the parenchyma of the adipose tissue in neutrophils by in adipose tissue neutrophils in fat of high-fat and 7 high-fat but established adipose tissue by as by macrophage and in adipose tissue of and and 7 and and the of expression that of in intra-abdominal fat of tissue demonstrate that neutrophils transiently infiltrate intra-abdominal adipose tissue early in the of by the infiltration of adipose tissue by the of we an in the of neutrophils the We the in neutrophils the of the in We by neutrophils of of the neutrophils the and of by the of neutrophils the the in the of neutrophils and in the of of the of in the we the of as the by and that neutrophil (3 in that of neutrophils the in the by the neutrophil neutrophil of by the of neutrophils the of neutrophils that of and an in the early after initiating high-fat feeding in that of neutrophils and the of neutrophils and the of neutrophils of of neutrophils by of by as in in the of are of of neutrophils and and the neutrophils and of neutrophils of of in the neutrophils in the in the of of neutrophils in the of the and neutrophils are the in neutrophil is by of by and we neutrophil in and of of in the of of by and and the of of neutrophils and in in the of the of that in the of the that the is the of neutrophil in the we of neutrophils the in the and the of neutrophils the of and the of neutrophils in neutrophils by and neutrophils the are of neutrophils in neutrophil by the neutrophil we the of and the an of the of by neutrophils the in the and in the of demonstrate that and are of the of the and are of by and by of neutrophils in the of the of are of in in is of the of is we the of the that is of in and in inflammation and We the the of neutrophils in and in the by neutrophils we demonstrate an and the and of by of and of the that of neutrophils the of the of in the and of the in of and in of neutrophils we that of the of by the the that the neutrophils and is by the and by neutrophils and neutrophil and expression of in in by of in are of neutrophils the are of neutrophils in of and and by and of by the of of are of neutrophils infiltrate adipose tissue macrophage we C57BL/6J mice, obesity high-fat high-fat an of in as early as after of high-fat feeding and high-fat mice, in of in adipose tissue the of adipose tissue we of adipose tissue the the neutrophil adipose tissue expression and and and and of adipose tissue expression of in is in Mean periepdidymal fat expression and and 7 and in expression in in expression in adipose tissue and high-fat and and neutrophils that that of adipose tissue the the of neutrophils the parenchyma of the adipose tissue in neutrophils by in adipose tissue neutrophils in fat of high-fat and 7 high-fat but established adipose tissue by as by macrophage and in adipose tissue of and and 7 and and the of expression that of in intra-abdominal fat of tissue demonstrate that neutrophils transiently infiltrate intra-abdominal adipose tissue early in the of by the infiltration of adipose tissue by the of we an in the of neutrophils the We the in neutrophils the of the in We by neutrophils of of the neutrophils the and of by the of neutrophils the the in the of neutrophils and in the of of the of in the we the of as the by and that neutrophil (3 in that of neutrophils the in the by the neutrophil neutrophil of by the of neutrophils the of neutrophils that of and an in the early after initiating high-fat feeding in that of neutrophils and the neutrophils in the in the of of neutrophils in the of the and neutrophils are the neutrophil is by of by and we neutrophil in and of of in the of of by and and the of of neutrophils and in in the of the of that in the of the that the is the of neutrophil in the we of neutrophils the in the and the neutrophil by the neutrophil we the of and the an of the of by neutrophils the in the and in the of demonstrate that and are of the of the is we the of the that is of in and in inflammation and We the the of neutrophils in and in the by neutrophils we demonstrate an and the and of by of and of the that of neutrophils the of the of in the and of the in of and in of neutrophils we that of the of by the the that the neutrophils and is by the and by neutrophils and obesity and the the adipose tissue of that fat is of the of obesity an in fat inflammation in fat in the of of of fat by of an of and the in intra-abdominal fat by of fat in of fat adipose tissue in obesity in the of fat the adipose tissue early in the of high-fat feeding of neutrophils transiently infiltrate the parenchyma of intra-abdominal adipose and in neutrophils in that is by and by the neutrophil but is of is by the of by neutrophil and that inflammatory is by inflammatory by neutrophils is in inflammation an the that adipose tissue in high-fat feeding the of adipose tissue inflammation in by the that the is in adipose tissue in obesity and of the in adipose tissue in obesity of inflammatory as of in adipose tissue. of in adipose in and and in fat and as as an as and inflammatory of and and the of the adipose tissue as an infiltration of into adipose tissue is macrophage in adipose and and in by inflammatory and and inflammatory of and that adipose tissue inflammation may inflammation and the the inflammatory cascade is in obesity unknown. are the demonstrate that high-fat feeding of neutrophils intra-abdominal tissue. inflammatory as an early high-fat and inflammatory infiltration into adipose tissue of infiltrate adipose tissue adipose tissue and obesity macrophage and in adipose tissue of and neutrophils are in adipose infiltration the of initiating high-fat feeding and adipose tissue and obesity neutrophil infiltration into adipose tissue is is neutrophil neutrophils of infiltration and and by adipose tissue in obesity of in adipose tissue. of in adipose may as as and and of the adipose that neutrophil are in the of adipose tissue in and inflammation in adipose inflammation by and in adipose tissue infiltration of neutrophils may that in high-fat feeding neutrophils are the adipose tissue infiltrate the parenchyma and are in in an of neutrophils is by neutrophil and of neutrophil an the of in the the of of the of neutrophils and and the of by and the of by neutrophils and of inflammatory infiltration into adipose tissue the of obesity is by the in of adipose tissue in the of adipose tissue and obesity and macrophage infiltration inflammatory and of high-fat the of macrophage infiltration into intra-abdominal adipose tissue infiltration of in adipose tissue is in and of infiltration of in adipose tissue is in infiltration into fat of and the of still the and adipose tissue in in the in adipose tissue inflammation and of infiltration of into adipose in adipose tissue and of in adipose and but adipose tissue inflammation is the of neutrophils are in that neutrophils in adipose tissue and of the and is of that of and into is the of an inflammatory but the of inflammatory as and in of neutrophils in the and of of and in the of the inflammatory cascade in inflammatory in of neutrophils in the and of of the of adipose tissue inflammation as neutrophil infiltration in initiating the inflammatory cascade in high-fat obesity and the the adipose tissue of that fat is of the of obesity an in fat inflammation in fat in the of of of fat by of an of and the in intra-abdominal fat by of fat in of fat adipose tissue in obesity in the of fat the adipose tissue early in the of high-fat feeding of neutrophils transiently infiltrate the parenchyma of intra-abdominal adipose and in neutrophils in that is by and by the neutrophil but is of is by the of by neutrophil and that inflammatory is by inflammatory by neutrophils is in inflammation an the that adipose tissue in high-fat feeding the of adipose tissue inflammation in by the that the is in adipose tissue in obesity and of the in adipose tissue in obesity of inflammatory as of in adipose tissue. of in adipose in and and in fat and as as an as and inflammatory of and and the of the adipose tissue as an infiltration of into adipose tissue is macrophage in adipose and and in by inflammatory and and inflammatory of and that adipose tissue inflammation may inflammation and the the inflammatory cascade is in obesity unknown. are the demonstrate that high-fat feeding of neutrophils intra-abdominal tissue. inflammatory as an early high-fat and inflammatory infiltration into adipose tissue of infiltrate adipose tissue adipose tissue and obesity macrophage and in adipose tissue of and neutrophils are in adipose infiltration the of initiating high-fat feeding and adipose tissue and obesity neutrophil infiltration into adipose tissue is is neutrophil neutrophils of infiltration and and by adipose tissue in obesity of in adipose tissue. of in adipose may as as and and of the adipose that neutrophil are in the of adipose tissue in and inflammation in adipose inflammation by and in adipose tissue infiltration of neutrophils may that in high-fat feeding neutrophils are the adipose tissue infiltrate the parenchyma and are in in an of neutrophils is by neutrophil and of neutrophil an the of in the the of of the of neutrophils and and the of by and the of by neutrophils and of inflammatory infiltration into adipose tissue the of obesity is by the in of adipose tissue in the of adipose tissue and obesity and macrophage infiltration inflammatory and of high-fat the of macrophage infiltration into intra-abdominal adipose tissue infiltration of in adipose tissue is in and of infiltration of in adipose tissue is in infiltration into fat of and the of still the and adipose tissue in in the in adipose tissue inflammation and of infiltration of into adipose in adipose tissue and of in adipose and but adipose tissue inflammation is the of neutrophils are in that neutrophils in adipose tissue and of the and is of that of and into is the of an inflammatory but the of inflammatory as and in of neutrophils in the and of of and in the of the inflammatory cascade in inflammatory in of neutrophils in the and of of the of adipose tissue inflammation as neutrophil infiltration in initiating the inflammatory cascade in high-fat is by and and