Mast cell and heparin promote adipogenesis in superficial fascia of rats

Abstract

Fascial adipocytes are recently identified as a unique population of adipose cells, which have different developmental origins, anatomical locations, cytological and functional characteristics compared with subcutaneous or visceral adipocytes. Superficial fascia in rats (also in pigs but not obviously in mice) contains numbers of lineage committed preadipocytes which possess adipogenic potential in vivo. The present study aimed to investigate the physiological factors that contribute to fascial adipogenesis in rats. We detected that mast cells, adipose progenitor cells, and mature adipocytes distributed in certain fascia areas were closely associated with each other, and numerous heparin-loaded granules released from mast cells were distributed around fascial preadipocytes. The culture supernatants of rat peritoneal mast cells and RBL-2H3 mast cells contained 20–30 μg/ml of heparin, effectively activated PPAR-responsive luciferase activity, promoted mRNA and protein expressions of key adipogenic genes, and hence increased adipogenic differentiation of fascia- or epididymal adipose-derived stromal cells. Adipogenic effects of mast cell supernatants were mimicked by heparin but not by histamine or 5-hydroxytryptamine, and were antagonized by protamine sulfate. In rats, local administration of heparin-loaded microspheres for 30 days induced adipogenesis in local areas of superficial fascia. This adipogenic effects of heparin might be related by chain length of glucosamine units, because heparin stimulated stronger adipogenesis than dalteparin and enoxaparin with relatively short chains. Our findings suggested that mast cell and its granule heparin could serve as the endogenous physiological factors to initiate and accelerate local adipogenesis in superficial fascia, or in adipose tissue with the fascia naturally embedded inside.