Chronic endothelin‐1 infusion causes adipocyte hyperplasia in rats

ObjectiveThe aim of this study was to investigate the regulatory mechanism of endothelin‐1 (ET‐1), an endothelium‐derived vasoconstrictor, on adipogenesis in vitro and in vivo.Methods3T3‐L1 preadipocytes were used to explore the mechanisms mediating ET‐1 actions on preadipocyte proliferation and adipocyte differentiation. To investigate the in vivo effect of ET‐1, male Sprague‐Dawley rats were infused with ET‐1 or saline for 4 weeks via intraperitoneally implanted osmotic pumps, and the fat pad weight and adipocyte size of adipose tissues were measured.ResultsET‐1 stimulated preadipocyte proliferation and increased the cell number at the mitotic clonal expansion stage of adipocyte differentiation via the endothelin A receptor (ETAR) and activation of the protein kinase C (PKC) pathway. ET‐1, via ETAR, inhibited adipocyte differentiation partially through an ERK‐dependent pathway. Furthermore, no significant difference in the body weight and fat pad weight was observed in either ET‐1‐ or saline‐infused rats. Compared with saline‐infused rats, the adipocyte cell number was significantly increased but the adipocyte size was significantly decreased in ET‐1‐infused rats.ConclusionsChronic ET‐1 infusion increased the number of small adipocytes without the change of white adipose tissue mass in rats, which were associated with ET‐1‐stimulated preadipocyte proliferation, but not ET‐1‐suppressed adipocyte differentiation.