Rosiglitazone promotes development of a novel adipocyte population from bone marrow–derived circulating progenitor cells
Joseph T. Crossno, Susan M. Majka, Todd Grazia, Ronald G. Gill, Dwight J. Klemm
Joseph T. Crossno, Susan M. Majka, Todd Grazia, Ronald G. Gill, Dwight J. Klemm
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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 5

Microscopic observation of GFP+ ML adipocytes isolated by collagenase digestion.

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Microscopic observation of GFP+ ML adipocytes isolated by collagenase di...
(A) Omental and dorsal intrascapular adipose tissue was isolated from GFP+ BMT mice fed ROSI-impregnated chow for 7 weeks. The tissue was digested with collagenase, and adipocytes were isolated by flotation. Adipocytes were then subjected to flow sorting to separate GFP+ and GFP– cells. Isolated cells were examined by phase-contrast and fluorescence digital deconvolution microscopy to evaluate morphology and GFP expression. Shown are representative phase-contrast and fluorescence images of GFP+ ML adipocytes (MLAs) compared with a GFP– unilocular white adipocyte (from omental tissue) and a GFP– ML brown adipocyte (from dorsal intrascapular brown fat). Digital overlay of GFP fluorescence signal and phase-contrast images in shown. Scale bar (red): 100 μm. (B) Phase-contrast, fluorescence, and digital overlay images of adipocytes isolated by collagenase digestion and flotation from GFP+ BMT mice fed ROSI-impregnated diet for 7 weeks. The image shows the substantial number of GFP+ adipocytes present in the total adipocyte population.