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. https://doi.org/10.1172/JCI19246.
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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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Adipose tissue transcripts whose abundance was correlated with body mass...
Adipose tissue transcripts whose abundance was correlated with body mass in mice. The expression of more than 12,000 transcripts in parametrial and epididymal adipose tissue was monitored in C57BL/6J mice whose body mass varied secondary to sex, diet, or mutations in the agouti (Ay/+) or leptin (Lepob/ob) loci. Using Kendall’s τ, a nonparametric correlation metric, we identified 1,304 transcripts that correlated significantly with body mass when the false discovery rate was held to 0.03. Examples of adipose tissue transcripts whose expression correlated with body mass include (a) Csf1r and (b) CD68 antigen (Cd68), which correlated positively with body mass, (c) succinate dehydrogenase complex, subunit B, iron sulfur (Ip) (Sdhb), and (d) ubiquinol–cytochrome c reductase subunit (Uqcr), which correlated negatively with body mass. Gray and black symbols denote female and male mice, respectively. +, lean; triangles, Ay/+; squares, DIO; circles, Lepob/ob mice.