title: Obesity is associated with macrophage accumulation in adipose tissue.
abstract: Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-alpha expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.
authors.affiliation: Division of Moleuclar Genetics, Department of Pediatrics, Columbia University, New York, New York 10032, USA.
authors.forename: Stuart P
authors.initials: SP
authors.lastname: Weisberg
authors.forename: Daniel
authors.initials: D
authors.lastname: McCann
authors.forename: Manisha
authors.initials: M
authors.lastname: Desai
authors.forename: Michael
authors.initials: M
authors.lastname: Rosenbaum
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Ferrante
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001835:Body Weight; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009765:Obesity / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015850:Interleukin-6; D017493:Leukocyte Common Antigens; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496319:NOS2 protein, human; C496317:Nos2 protein, mouse