Glycosylphosphatidylinositol-anchored proteins coordinate lipolysis inhibition between large and small adipocytes

Abstract

In response to palmitate, the antidiabetic sulfonylurea drug glimepiride, phosphoinositoglycans, or H 2O 2, the release of the glycosylphosphatidylinositol-anchored and cyclic adenosine monophosphate–degrading phosphodiesterase Gce1 from adipocytes into small vesicles (adiposomes) and its translocation from adiposomes to cytoplasmic lipid droplets (LD) of adipocytes have been reported. Here the role of Gce1-harboring adiposomes in coordinating lipolysis between differently sized adipocytes was studied. Separate or mixed populations of isolated epididymal rat adipocytes of small and large size and native adipose tissue pieces from young and old rats were incubated with exogenous adiposomes or depleted of endogenous adiposomes and then analyzed for translocation of Gce1 and lipolysis in response to above antilipolytic stimuli. Large compared with small adipocytes are more efficient in releasing Gce1 into adiposomes but less efficient in translocating Gce1 from adiposomes to LDs. Maximal lipolysis inhibition by above antilipolytic stimuli, but not by insulin, was observed with mixed populations of small and large adipocytes (1:1 to 1:2) rather than with separate populations. In mixed adipocyte populations and adipose tissue pieces from young, but not old, rats, lipolysis inhibition by above antilipolytic stimuli, but not by insulin, was dependent on the function of Gce1-harboring adiposomes. Inhibition of lipolysis in rat adipose tissue in response to palmitate, glimepiride, and H 2O 2 is coordinated via the release of adiposome-associated and glycosylphosphatidylinositol-anchored Gce1 from large “donor” adipocytes and their subsequent translocation to the LDs of small “acceptor” adipocytes. This transfer of antilipolytic information may be of pathophysiologic relevance.