Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells.
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/EBPalpha, and PPARgamma 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.
Crossno
Joseph T
JT
Research Section, Veterans Affairs Medical Center, Denver, CO, USA.
Majka
Susan M
SM
Grazia
Todd
T
Gill
Ronald G
RG
Klemm
Dwight J
DJ
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000032:analysis; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D018845:CD11 Antigens / Q000032:analysis; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects*; D017364:Collagenases / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020738:Leptin / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008858:Microscopy, Phase-Contrast; D047495:PPAR gamma / Q000032:analysis; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
D052242:Adiponectin; D018845:CD11 Antigens; D002352:Carrier Proteins; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D020738:Leptin; D047495:PPAR gamma; D000070778:Perilipin-1; D010750:Phosphoproteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens; D017364:Collagenases