Acylation Stimulating Protein (ASP) Deficiency and Altered Adipose Tissue in Alternative Complement Pathway Knockout Mice

Acylation stimulating protein (C3adesArg/ASP) is an adipokine that acts on its receptor C5L2 to stimulate triglyceride (TG) synthesis in adipose tissue. The present study investigated ASP levels in mouse models of obesity and leanness and the effect of ASP deficiency in C3 knockout (C3KO) mice on adipose tissue morphology. Plasma ASP levels in wildtype (WT) mice correlated positively with plasma non-esterified fatty acids (NEFA) (R=0.664, p<0.001) and total cholesterol (R=0.515, p<0.001). Plasma ASP was increased by 85% in obese ob/ob leptin-deficient mice and decreased in lean DGAT1 KO mice (-54%) and C/EBPαβ/β  transgenic mice (-70%) compared to WT . Mice lacking alternative complement factor B or adipsin (FBKO or ADKO), required for ASP production, were also ASP deficient. Both FBKO and C3KO had delayed postprandial TG and NEFA clearance on low fat (LF) and high fat (HF) diets, suggesting lack of ASP, not C3, drives the metabolic phenotype. Adipocyte size distribution in C3KO mice was polarized (increased number of both small and large cells), with decreased adipsin expression (-33% gonadal HF), DGAT1 expression (-31% to 50%) and DGAT activity (-41%). Overall a reduction/deficiency in ASP is associated with an anti-adipogenic state and ASP may provide a target for controlling fat storage.