Novel roles for acylation stimulating protein/C3adesArg: a review of recent in vitro and in vivo evidence.

Recent experimental evidence is shedding more light on the physiological actions of acylation-stimulating protein (ASP)/C3adesArg. The role of ASP in regulating lipid metabolism has primarily focused on its participation in the stimulation of triglyceride synthesis (TGS) and glucose transport. Although there is no doubt that ASP, an adipocyte-produced hormone, plays a key physiological role, accumulating evidence suggests that the effects of ASP go beyond its acute effects on lipid metabolism. In this review, we present novel findings of ASP/C3adesArg effects on preadipocyte differentiation. In 3T3-L1 and 3T3-F442A cells, ASP can substitute for insulin and enhance differentiation as measured by intracellular lipid droplet accumulation, clonal expansion, and increased expression of differentiation markers. Specifically, ASP increased basal TGS by 250% after 9 days differentiation, with similar effects induced by insulin. With ASP treatment, expression of C/EBPdelta was up-regulated early in differentiation (day 2) and decreased thereafter. Expression of PPARgamma and late markers of differentiation, such as adipsin and diacylglycerol acyltransferase-1, were also increased. Effects on clonal expansion were indicated by a twofold increase in [(3)H] thymidine incorporation in 3T3-L1 cells compared to treatment with IBMX + DX alone. Further, the effects of ASP extended beyond adipose tissue to endocrine effects on hormone secretion of insulin (pancreatic cells); cytokines TNFalpha, IL-1beta, and IL-6 (myeloid cells); prolactin, growth hormone, and adrenocorticotropin (pituitary cells). Finally, the potential implication of C5L2, the newly discovered ASP receptor, and its expression profile in various tissues are discussed relative to ASP function.