Adipocyte macrophage colony-stimulating factor is a mediator of adipose tissue growth.
Adipose tissue growth results from de novo adipocyte recruitment (hyperplasia) and increased size of preexisting adipocytes. Adipocyte hyperplasia accounts for the severalfold increase in adipose tissue mass that occurs throughout life, yet the mechanism of adipocyte hyperplasia is unknown. We studied the potential of macrophage colony-stimulating factor (MCSF) to mediate adipocyte hyperplasia because of the profound effects MCSF exerts on pluripotent cell recruitment and differentiation in other tissues. We found that MCSF mRNA and protein were expressed by human adipocytes and that adipocyte MCSF expression was upregulated in rapidly growing adipose tissue that encircled acutely inflamed bowel and in adipose tissue from humans gaining weight (4-7 kg) with overfeeding. Localized overexpression of adipocyte MCSF was then induced in rabbit subcutaneous adipose tissue in vivo using adenoviral-mediated gene transfer. Successful overexpression of MCSF was associated with 16-fold increases in adipose tissue growth compared with a control adenovirus expressing beta-galactosidase. This occurred in the absence of increased cell size and in the presence of increased nuclear staining for MIB-1, a marker of proliferation. We conclude that MCSF participates in adipocyte hyperplasia and the physiological regulation of adipose tissue growth.
Levine
J A
JA
Department of Medicine, Endocrine Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. Levine.james@Mayo.edu
Jensen
M D
MD
Eberhardt
N L
NL
O'Brien
T
T
D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D000818:Animals; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor