Upregulation of Lipid Synthesis in Small Rat Adipocytes by Microvesicle‐Associated CD73 From Large Adipocytes

Abstract

Filling‐up lipid stores is critical for size increase of mammalian adipocytes. The glycosylphosphatidylinositol (GPI)‐anchored protein, CD73, is released from adipocytes into microvesicles in response to the lipogenic stimuli, palmitate, the antidiabetic sulfonylurea drug glimepiride, phosphoinositolglycans (PIG), and H2O2. Upon incubation of microvesicles with adipocytes, CD73 is translocated to cytoplasmic lipid droplets (LD) and esterification is upregulated. The role of CD73‐harboring microvesicles in coordinating esterification between differently sized adipocytes was studied here. Populations consisting of either small or large or of both small and large isolated rat adipocytes as well as native adipose tissue pieces from young and old rats were incubated with or depleted of endogenous microvesicles and analyzed for translocation of CD73 and esterification in response to the lipogenic stimuli. Large adipocytes exhibited higher and lower efficacy in releasing CD73 into microvesicles and in translocating CD73 to LD, respectively, compared to small adipocytes. Populations consisting of both small and large adipocytes were more active in esterification in response to the lipogenic stimuli than either small or large adipocytes. With both adipocytes and adipose tissue pieces from young rats esterification stimulation by the lipogenic stimuli was abrogated by depletion of CD73‐harboring microvesicles from the incubation medium and interstitial spaces, respectively. In conclusion, stimulus‐induced lipid synthesis between differently sized adipocytes is controlled by the release of microvesicle‐associated CD73 from large cells and its subsequent translocation to LD of small cells. This information transfer via microvesicles harboring GPI‐anchored proteins may shift the burden of triacylglycerol storage from large to small adipocytes.

Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

“…Proteomic profiling studies of EVs released by adipocyte cell models have been documented including that of hypoxic 3T3‐L1 cells and of animal models of obesity and diabetes but to date not much information is available for circulating EVs in human obesity. Available literature from in vitro systems suggests that EVs from adipocytes contain protein and RNA species involved in regulating lipid metabolism and adipokine production …”

“…Adipocytes have been shown to produce EVs of heterogeneous sizes which contribute to regulate lipid deposition and angiogenesis, reviewed in . Deng et al .…”

Therapeutic potential of antisense oligonucleotides for the management of dyslipidemia

“…For the moment, the exact nature and physiological role of this novel adipocyte population are still misunderstood, but these results suggest they may be implicated in the metabolic dysfunction of white adipose tissues associated with ectopic fat accumulation, as shown by the presence of hepatic steatosis [64]. A recent study suggests a molecular cross-talk between larger adipocytes and these small adipocytes that regulates the fatty acid uptake capacity of the latter [66].…”

PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition

“…This would explain the increase of PTRF and caveolin-1 over time in adipocytes treated with rPTRF. Muller et al reported that adipocytes can enlarge when treated with certain EV [14] which triggered the expression of some adipogenic genes among which are regulators of caveola expression [19]. We hypothesize that the larger size of the adipocytes treated with rPTRF may be explained by an increased number of caveolae, thus allowing the adipocyte to have a membrane reservoir to rapidly increase cell surface.…”