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Acylation Stimulating Protein (ASP) is one of the factors that control adipose tissue function. It was initially identified from human plasma, J Biol Chem. 1989 Jan 5;264(1):426-30  and determined to be a derivative of the 3rd complement component (C3).  Arginine removal from activated C3 (C3a) by carboxypeptidase results in C3a-desArg, also known as ASP. Human fat cells have been shown to have mRNA for Adipsin (complement factor D), C3 and factor B, all of which are components necessary to generate  C3a, the precursor for ASP.  Basal production of ASP in adipocytes is dependent on adipocyte differentiation, with ASP production increasing after 7 days of adipocyte differentiation. Eur J Clin Invest. 1995 Nov;25(11):817-25.  While ASP is produced by the interaction of C3, factor B and Adipsin in the alternate complement pathway, it can also be potentially generated by the classical complement pathway as well as the lectin pathway. Plasma concentrations of ASP in normal adults range from 10-58 nM with no gender related differences. Eur J Clin Invest. 1999 Aug;29(8):679-86.


Actions of ASP

ASP injection intraperitoneally into lean mice reduces triglyceride levels by 40%, Am J Physiol. 1999 Sep;277(3 Pt 1):E474-80   with enhanced triglyceride clearance being demonstrable in ob/ob and db/db mice which are hypertriglyceridemic and hyperinsulinaemic. Int J Obes Relat Metab Disord. 2001 May;25(5):705-13     ASP increases triglyceride synthesis in human adipocytes  and skin fibroblasts by stimulating fatty acid incorporation into adipose triglyceride. Semin Cell Dev Biol. 1999 Feb;10(1):31-41  This triglyceride synthesis stimulation is more potent than that seen with insulin,   Biochemistry. 1994 Aug 16;33(32):9489-95   as well as synergistic, with the combined effect of ASP and insulin being a complete (97%) re-esterification and storage of fatty acid available.  The ASP effect is primarily on triglyceride enzyme activation with the predominant effect being on the enzyme diacylglycerol acyltransferase. Lipids. 1991 Jul;26(7):495-9.  ASP stimulates triglyceride synthesis in differentiated adipocytes than in preadipocytes. J Surg Res. 1989 May;46(5):470-3. The rate of triglyceride clearance from plasma correlates with plasma levels of ASP. J Lipid Res. 1989 Nov;30(11):1727-33  Thus, ASP may facilitate signalling between the circulation and the adipose tissue to modulate the storage function of fatty tissue. Note that C3a also is a potent stimulator of triglyceride synthesis in adipocytes and pre-adipocytes, and conversion to ASP is not necessary to effect this action.  J Lipid Res. 1997 Dec;38(12):2492-501   


While ASP increases lipogenesis in adipocytes, it also decreases lipolysis by inhibiting hormone sensitive lipoprotein lipase. J Biol Chem. 1999 Jun 25;274(26):18243-51   ASP also increases glucose transport by enhanced translocation of glucose transporters (GLUT1, GLUT3 and GLUT4) to the plasma membrane surface. Although C3a is an immune modulator in the myeloid system, C3ades-arginine (ASP) is not active in the immune system.  J Lipid Res. 1997 Dec;38(12):2492-501   

ASP may mediate its actions through as yet uncharacterized receptors. These receptors seem to be distinct from the receptor for C3a, as ASP binds to subcutaneous and omental adipocytes and pre-adipocytes despite a lack of demonstrable C3a receptor protein or mRNA at in the adipose tissue. Am J Physiol. 1999 May;276(5 Pt 1):E815-21.
Regulators of ASP

While glucose ,free fatty acids, LDL, VLDL, and HDL have little or no effect on ASP production, insulin increases ASP production 3 fold, while the postprandial rise in chylomicrons results in the strongest stimulus for ASP production (150 fold rise) in a dose dependent manner   J Lipid Res. 1997 Jan;38(1):1-11.  C3 mRNA levels correlate with plasma triglycerides, NEFA levels and leptin. These factors could up-regulate ASP production in the insulin-resistant state. TNF-alpha, IL-6 and glucocorticoids can influence C3, factor B, and Adipsin in obese subjects,  Diabetes Care. 2000 Jun;23(6):779-85.     thereby influencing ASP production. Exercise increases ASP acutely by up to 67% in athletes with relatively rapid return to normal levels afterwards. International Journal of Obesity (2005) 29, 632-638
ASP and Obesity

ASP levels increase post prandially. In lean controls, no net production of ASP is demonstrable in the fasting state. In contrast, Morbidly obese subjects have higher ASP levels than controls,  Int J Obes Relat Metab Disord. 1995 Sep;19(9):604-9    even in the fasted state.  J Lipid Res. 2000 Dec;41(12):1963-8.  Obese humans have 58-400% increase in ASP above normal.  It is likely that the higher circulating ASP levels in the obese might continue to enhance the triglyceride storage, since adipocytes in the obese subjects remain as sensitive to the effects of ASP as in normal weight subjects.   A 4 week fast resulted in a reduction of ASP to normal levels in these obese subjects. Weight loss has been shown to decrease ASP levels  Atherosclerosis. 1990 Mar;81(2):111-8.  with normalisation of ASP levels. The precursors of ASP, namely plasma C3, factor B and Adipsin also decrease with weight loss.
ASP and Diabetes

Type 2 diabetic patients have higher levels of ASP, C3, factor B and Adipsin. Arterioscler Thromb Vasc Biol. 2001 Jun;21(6):1034-9   Obesity could be a confounding factor in these patients, as the increase in ASP in the type 2 diabetic patients was only to a level comparable to non-diabetic subjects of matched weight. While ASP levels correlated with lipids and blood glucose in non-diabetic subjects, no such correlation was demonstrated in diabetics, possibly due to a dysregulation in ASP production or metabolism.
ASP and Miscellaneous Conditions

HyperApoB subjects who tend to have increased incidence of coronary artery disease have a dysfunction of the ASP pathway. J Clin Invest. 1990 Mar;85(3):722-30.  HyperApoB subjects have higher levels of plasma ASP, probably due to decreased responsiveness to ASP at the adipose tissue  resulting in a compensatory increase in ASP levels. Patients with anorexia nervosa have lower levels of plasma C3, factor B and Adipsin which increase with weight gain.