Obesity is associated with macrophage accumulation in adipose tissue
Stuart P. Weisberg ... Rudolph L. Leibel, Anthony W. Ferrante Jr.
Stuart P. Weisberg ... Rudolph L. Leibel, Anthony W. Ferrante Jr.
Published December 15, 2003
Citation Information: J Clin Invest. 2003;112(12):1796-1808. doi:10.1172/JCI19246.
View: Text | PDF
Categories: Article Metabolism

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-α 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

Stuart P. Weisberg, Daniel McCann, Manisha Desai, Michael Rosenbaum, Rudolph L. Leibel, Anthony W. Ferrante Jr.

×
Options: View larger image (or click on image)
Adipose tissue macrophages express proinflammatory factors. Perigonadal ...

Figure 8

Adipose tissue macrophages express proinflammatory factors. Perigonadal adipose tissue was collected from female B6.V Lepob/ob mice, digested, and centrifuged to yield a buoyant adipocyte-enriched cell population (gray bars) and a pellet of SVCs. The SVCs were separated into F4/80+ macrophages (black bars) and F4/80– populations (white bars) via FACS. Quantitative RT-PCR was used to measure the relative expression of three proinflammatory genes (Tnfa, Nos2, and Il6). Expression of Tnfa was limited almost exclusively to adipose tissue macrophages. F4/80– SVCs did not express detectable amounts of F4/80 or Tnfa (as indicated by asterisks). The adipocyte-enriched fractions expressed Tnfa at levels commensurate F4/80 expression and consistent with macrophage contamination. Nos2 was expressed by both macrophages and F4/80– SVCs, and Il6 was detectably expressed by all three populations in adipose tissue.