Folate receptor expression on murine and human adipose tissue macrophages

Objective and design: Adipose tissue macrophages (ATMs) have been implicated in a number of obesity-related diseases. Because the activated macrophages associated with many types of autoimmune and inflammatory diseases express a folate receptor (FR) that can be exploited for FR-targeted drug delivery, we examined the visceral adipose tissue of obese mice and humans to determine whether ATMs also express FR that are accessible by folate conjugates. Material or subjects: C57BL/6 or FATSO mice fed on either a low- or high-fat diet were used in murine studies. Human adipose tissue were obtained from healthy volunteers during adipose reduction surgery. Methods: Visceral adipose tissue was collected from both obese mice and humans, collagenase digested, and stained with folate-Oregon Green and antibodies for macrophage markers including F4/80, mannose receptor (CD206), CD11b, and CD11c. Cells were then examined for expression of the above markers by flow cytometry. Furthermore, the ability of folate conjugates to target the FR-expressing ATMs in obese mice was evaluated in vivo. Results: A subset of the ATMs harvested from obese mice were found to express FR. Subpopulations of ATMs also simultaneously express both pro- and anti-inflammatory markers, and FR is expressed on both subsets. We then demonstrate that FR-expressing ATMs can be targeted with folate-linked fluorescent dyes in vivo. Conclusions: FR are expressed on multiple subsets of ATMs and these subsets can be targeted with folate-linked drugs, allowing for the possible development of FR-targeted therapies for obesity-related inflammatory diseases.