Adipocyte macrophage colony-stimulating factor is a mediator of adipose tissue growth.

TLDR

Adipose tissue expands through hyperplasia and hypertrophy, yet the mechanism driving hyperplasia remains unknown. The study examined whether macrophage colony‑stimulating factor (MCSF) mediates adipocyte hyperplasia, given its role in recruiting and differentiating pluripotent cells elsewhere. Adipocyte MCSF was overexpressed locally in rabbit subcutaneous fat via adenoviral gene transfer to test its effect on tissue growth. MCSF is expressed by human adipocytes and is upregulated in rapidly expanding fat; adenoviral overexpression in rabbits caused a 16‑fold increase in adipose growth without enlarging cells but with heightened proliferation, indicating MCSF drives adipocyte hyperplasia.

Abstract

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.