Rosiglitazone promotes development of a novel adipocyte population from bone marrow–derived circulating progenitor cells
Joseph T. Crossno, … , Ronald G. Gill, Dwight J. Klemm
Joseph T. Crossno, … , Ronald G. Gill, Dwight J. Klemm
Published December 1, 2006
Citation Information: J Clin Invest. 2006;116(12):3220-3228. https://doi.org/10.1172/JCI28510.
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Research Article Metabolism

Rosiglitazone promotes development of a novel adipocyte population from bone marrow–derived circulating progenitor cells

Abstract

Obesity and weight gain are characterized by increased adipose tissue mass due to an increase in the size of individual adipocytes and the generation of new adipocytes. New adipocytes are believed to arise from resident adipose tissue preadipocytes and mesenchymal progenitor cells. However, it is possible that progenitor cells from other tissues, in particular BM, could also contribute to development of new adipocytes in adipose tissue. We tested this hypothesis by transplanting whole BM cells from GFP-expressing transgenic mice into wild-type C57BL/6 mice and subjecting them to a high-fat diet or treatment with the thiazolidinedione (TZD) rosiglitazone (ROSI) for several weeks. Histological examination of adipose tissue or FACS of adipocytes revealed the presence of GFP+ multilocular (ML) adipocytes, whose number was significantly increased by ROSI treatment or high-fat feeding. These ML adipocytes expressed adiponectin, perilipin, fatty acid–binding protein (FABP), leptin, C/EBPα, and PPARγ but not uncoupling protein–1 (UCP-1), the CD45 hematopoietic lineage marker, or the CDllb monocyte marker. They also exhibited increased mitochondrial content. Appearance of GFP+ ML adipocytes was contemporaneous with an increase in circulating levels of mesenchymal and hematopoietic progenitor cells in ROSI-treated animals. We conclude that TZDs and high-fat feeding promote the trafficking of BM-derived circulating progenitor cells to adipose tissue and their differentiation into ML adipocytes.

Authors

Joseph T. Crossno, Susan M. Majka, Todd Grazia, Ronald G. Gill, Dwight J. Klemm

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Figure 6

GFP+ ML adipocytes express C/EBPα, PPARγ, adiponectin, FABP, perilipin, leptin, and β3-AR but not UCP-1 and have high mitochondrial content.

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GFP+ ML adipocytes express C/EBPα, PPARγ, adiponectin, FABP, perilipin, ...
(A) cDNA was prepared from RNA from white (from omental adipose tissue), brown (from dorsal intrascapular adipose tissue), and ML adipocytes isolated by collagenase digestion and flotation as described in Methods. Equal amounts of cDNA (1 μg) were subjected to PCR with validated primer sets for the targets indicated to the left of each gel photograph. PCR reactions were then resolved on 2% agarose gels run in the presence of ethidium bromide. Fluorescence photographs of the gels were captured to computer, and band intensities were measured using ImageJ software. Representative gel photographs are shown in the left column. Densitomentry data were averaged over 3 experiments and corrected for differences in β-actin levels. Average band intensities are shown in the corresponding bar graphs to the right of each gel photograph. (B) Mitotracker Red 580 staining was performed on minced white adipose tissue fragments from GFP+ BMT mice fed ROSI-impregnated chow for 7 weeks. Representative fluorescence deconvolution images for GFP and Mitotracker signals, as well as a digital overlay of GFP and Mitotracker signals, are shown (yellow: GFP plus Mitotracker; red or orange: Mitotracker plus little or no GFP). The general location of white (W) and ML adipocytes is indicated by the white ovals.