Adipsin/Acylation Stimulating Protein System in Human Adipocytes: Regulation of Triacylglycerol Synthesis

Abstract

Through their capacity to store fatty acids as triacylglycerol molecules, adipocytes serve a vital physiologic role. This study presents further evidence that this process can be modulated in human adipocytes by the adipsin/acylation stimulating protein (ASP) pathway and suggests a novel function for the product of this system--ASP. The data demonstrate the following: (1) ASP stimulates triacylglycerol synthesis within adipocytes, and this occurs to a greater extent in differentiating than undifferentiated cells (242% +/- 32% vs 168% +/- 11%, p < 0.01, respectively, at an ASP concentration of 88 ng/mL; (2) ASP does not affect the Km for triacylglycerol synthesis but does substantially increase Vmax; (3) when ASP is generated in vitro through incubation of its precursor proteins under appropriate conditions, triacylglycerol synthesis increases to the same extent as when plasma-purified ASP is added to the medium; (4) human adipocytes contain mRNA for the specific serine protease adipsin and the two precursor proteins C3 and factor B required to interact for the production of ASP; and (5) the extent to which cultured differentiating adipocytes produce ASP is proportional to the degree to which they have accumulated triacylglycerol mass during differentiation (r2 = 0.7523, p < 0.0005). These findings provide the first evidence for the existence of the adipsin/ASP pathway in human adipocytes, and this may markedly enhance our understanding of the processes which regulate triacylglycerol clearance from plasma.

Troglitazone reduces hyperglycaemia and selectively acute-phase serum proteins in patients with Type II diabetes

“…Complement protein C3 was measured because it is a cytokine-inducible acute-phase plasma protein [20] and vital to all three complement activation pathways and defence against invading micro-organisms [21]. It is synthesized also in the adipose tissue [22] and has a connection to lipid metabolism through its cleavage product acylation stimulating protein (ASP) [23]. It has a critical role in triacylglycerol (TG) synthesis within adipocytes [23].…”

Apolipoprotein E and Complement C3 Polymorphism and Their Role in the Response to Gemfibrozil and Low Fat Low Cholesterol Therapy

“…In all cases, analyses were performed before and after interventions. The patients had been requested to consume a cholesterol-lowering diet (less than 30% of daily energy as fat and daily cholesterol intake < 200 mg, (19)) and were treated with gemfibrozil (Gevilon®, G decke Inc.) 900 mg at bedtime. They were advised to adhere to this diet during the experimental period (6 months).…”

“…A certain C4 allotype (C4B*QO) had higher prevalence in men with myocardial infarction (18). C3 was reported to be involved in the regulation of the adipsin/acylation stimulating protein system which seems to play a pivotal role in regulation of triacylglycerol removal from plasma (19). It was found that acylation stimulating protein is identical with the cleavage product of complement factor C3, named C3a-desArg, and stimulates triacylglycerol synthesis in human adipocytes.…”

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes

“…8,9 ASP is a potent stimulator of free fatty acid esterification into storage triglyceride in human adipocytes in vitro. 5,6,10 Recent studies indicate that chylomicrons and insulin increase both ASP and C3 production in human adipocytes. [11][12][13] While no direct role for C3 has been proposed, ASP appears to be an important determinant of postprandial lipemia in both human 14 and mouse models.…”