Lipoprotein lipase deficiency is associated with elevated acylation stimulating protein plasma levels

Abstract

Acylation stimulating protein (ASP, C3adesArg) is an adipose tissue derived hormone that stimulates triglyceride (TG) synthesis. ASP stimulates lipoprotein lipase (LPL) activity by relieving feedback inhibition caused by fatty acids (FA). The present study examines plasma ASP and lipids in male and female LPL-deficient subjects primarily with the P207L mutation, common in the population of Quebec, Canada. We evaluated the fasting and postprandial states of LPL heterozygotes and fasting levels in LPL homozygotes. Homozygotes displayed increased ASP (58-175% increase, P , 0.05-0.01), reduced HDL-cholesterol (64-75% decrease, P , 0.0001), and elevated levels of TG (19-38-fold, P , 0.0001) versus control (CTL) subjects. LPL heterozygotes with normal fasting TG (1.3-1.9 mmol/l) displayed increased ASP (101-137% increase, P , 0.05-0.01) and delayed TG clearance after a fatload; glucose levels remained similar to controls. Hypertriglyceridemics with no known LPL mutation also had increased ASP levels (63-192% increase, P , 0.001). High-TG LPL heterozygotes were administered a fatload before and after fibrate treatment. The treatment reduced fasting and postprandial plasma ASP, TG, and FA levels without changing insulin or glucose levels. ASP enhances adipose tissue fatty-acid trapping following a meal; however in LPL deficiency, high ASP levels are coupled with delayed lipid clearance.-Paglialunga, S., P.

Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and Insulin Resistance in Obesity

“…Indeed, other studies have pointed out a possible response of adipose tissue C3 production to feeding [ 7 , 8 , 9 ]. Furthermore, this response is not detectable at plasma levels [ 26 , 27 , 28 ]. Instead, high levels of C3 at the adipose tissue microenvironment have been proposed, which, with the help of adipsin (specifically produced in adipose tissue), could produce a peak of ASP at postprandial levels [ 8 , 27 ].…”

Effects of sugar‐sweetened beverages on plasma acylation stimulating protein, leptin and adiponectin: Relationships with Metabolic Outcomes

“…ASP is identical to the immune complement pathway cleavage product C3a‐des‐Arg, and is produced through interaction of three proteins of the alternate complement system; C3, factor B, and adipsin (factor D); all of which are synthesized and secreted by adipocytes . ASP increases triglyceride (TG) synthesis in adipose tissue through (i) increasing glucose transport via translocation of glucose transporters Glut 1, 2, and 3 ; (ii) stimulating fatty acid uptake and esterification ; (iii) increasing the activity of enzymes related to fat storage, such as diacylglycerol‐acyltransferase , (iv) inhibiting hormone sensitive lipase and thereby (v) enhancing the efficiency of lipoprotein lipase (LPL) by reducing fatty acid inhibition. Adiposity is an important determinant of circulating ASP levels, which are elevated in obese subjects and decrease with weight loss .…”

Relationship of C5L2 Receptor to Skeletal Muscle Substrate Utilization

“…ASP stimulates fatty acid esterification by increasing diacylglycerolacyltransferase (DGAT) activity which catalyzes the final step in triglyceride synthesis [12]. Furthermore, in vitro , ASP supplementation increased lipoprotein lipase (LPL) activity in adipose tissue, facilitating triglyceride accumulation [13], and, consequently, in LPL deficiency, plasma ASP levels are upregulated [14]. ASP also stimulates glucose uptake, inducing translocation of glucose transporters (Glut4 and Glut3) to the cell membrane in cultured human preadipocytes [15].…”