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.
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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.

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F4/80+ cells express macrophage markers. Perigonadal adipose tissue was ...

Figure 5

F4/80+ cells express macrophage markers. Perigonadal adipose tissue was collected from female B6.V Lepob/ob mice, digested, and centrifuged to yield a buoyant adipocyte-enriched cell population and a pellet of SVCs. The SVCs were separated into F4/80+ (black bars) and F4/80– (white bars) populations via FACS. Quantitative RT-PCR was used to measure the relative expression of macrophage markers (Emr1, Csf1r, Cd68) and an adipocyte-specific gene (Acrp30). Among the three isolated cell populations, the relative gene expression of macrophage markers was highest among the F4/80+ cells. *The F4/80– SVCs did not express detectable amounts (< 0.05 of mean of all populations) of the macrophage markers. The adipocyte-enriched population (gray bars) expressed small amounts of the macrophage markers (a), consistent with residual macrophage contamination seen by immunofluorescent staining of live cells (b). In the adipocyte-enriched fraction, large autofluorescent adipocyte cell membranes (green) are not recognized by fluorescently conjugated F4/80 antibody (red), but membrane staining of small nonautofluorescent cells is seen. Control fluorescently conjugated isotype antibody did not recognize these cells (c).