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

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. 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. Lipoprotein lipase (LPL) is a key enzyme involved in fat metabolism. In its active form as a dimer, LPL catalyzes the hydrolysis of triglyceride (TG) from both chylomicrons and VLDL, releasing nonesterified fatty acids (NEFA) which can be taken up by adipose tissue, to store as TG, or by the muscle to be used as an energy source (as reviewed in Ref. 1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar). LPL activity is highly regulated by several factors, including apolipoproteins, hormones, and even NEFA levels (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar). ApoCIII and TNF-α decrease LPL function, while apoCII, apoAV and both insulin and acylation stimulating protein (ASP, C3adesArg) enhance LPL activity (as reviewed in Ref. 2Paglialunga S. Cianflone K. Regulation of postprandial lipemia: an update on current trends.Appl. Physiol. Nutr. Metab. 2007; 32: 61-75Crossref PubMed Google Scholar). ASP is an adipose tissue derived hormone generated through the alternative complement pathway and is the cleavage product of complement C3 by adipsin (as reviewed in Ref. 3Cianflone K. Xia Z. Chen L.Y. Critical review of Acylation Stimulating Protein physiology in humans and rodents.Biochim. Biophys. Acta. 2003; 1609: 127-143Crossref PubMed Scopus (314) Google Scholar). ASP stimulates TG synthesis in adipocytes by increasing diacylglycerol acyltransferase (DGAT) activity, the final enzyme in the TG synthesis cascade (4Yasruel Z. Cianflone K. Sniderman A.D. Rosenbloom M. Walsh M. Rodriguez M.A. Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue.Lipids. 1991; 26: 495-499Crossref PubMed Scopus (118) Google Scholar). ASP acts through C5L2, a G protein-coupled receptor, to stimulate TG synthesis and glucose uptake (5Kalant D. Maclaren R. Cui W. Samanta R. Monk P.N. Laporte S.A. Cianflone K. C5L2 is a functional receptor for acylation stimulating protein.J. Biol. Chem. 2005; 280: 23936-23944Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar, 6Kalant D. Cain S.A. Maslowska M. Sniderman A.D. Cianflone K. Monk P.N. The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/Acylation-Stimulating Protein.J. Biol. Chem. 2003; 278: 11123-11129Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar). C5L2 is highly expressed in adipose tissue, muscle, and liver (5Kalant D. Maclaren R. Cui W. Samanta R. Monk P.N. Laporte S.A. Cianflone K. C5L2 is a functional receptor for acylation stimulating protein.J. Biol. Chem. 2005; 280: 23936-23944Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar, 7Okinaga S. Slattery D. Humbles A. Zsengeller Z. Morteau O. Kinrade M.B. Brodbeck R.M. Krause J.E. Choe H.R. Gerard N.P. et al.C5L2, a nonsignaling C5A binding protein.Biochemistry. 2003; 42: 9406-9415Crossref PubMed Scopus (213) Google Scholar). While insulin directly increases LPL activity in adipocytes (8Faraj M. Sniderman A.D. Cianflone K. ASP enhances in situ lipoprotein lipase activity by increasing fatty acid trapping in adipocytes.J. Lipid Res. 2004; 45: 657-666Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar), ASP stimulates LPL activity indirectly by enhancing cellular uptake and esterification of NEFA, thereby relieving feedback inhibition on LPL (8Faraj M. Sniderman A.D. Cianflone K. ASP enhances in situ lipoprotein lipase activity by increasing fatty acid trapping in adipocytes.J. Lipid Res. 2004; 45: 657-666Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar). Like insulin (9Farese Jr., R.V. Yost T.J. Eckel R.H. Tissue-specific regulation of lipoprotein lipase activity by insulin/glucose in normal-weight humans.Metabolism. 1991; 40: 214-216Abstract Full Text PDF PubMed Scopus (151) Google Scholar, 10Boivin A. Montplaisir I. Deshaies Y. Postprandial modulation of lipoprotein lipase in rats with insulin resistance.Am. J. Physiol. 1994; 267: E620-E627PubMed Google Scholar), ASP exerts an inhibitory effect on LPL activity in the muscle (11Faraj M. Cianflone K. Differential regulation of fatty acid trapping in mice adipose tissue and muscle by ASP.Am. J. Physiol. Endocrinol. Metab. 2004; 287: E150-E159Crossref PubMed Scopus (35) Google Scholar). Furthermore, in vivo antibody treatment that blocked ASP function in mice resulted in decreased LPL activity in adipose tissue and increased muscle LPL activity (12Cui W. Paglialunga S. Kalant D. Lu H. Roy C. Laplante M. Deshaies Y. Cianflone K. Acylation Stimulating Protein/C5L2 Neutralizing Antibodies alter Triglyceride Metabolism in vitro and in vivo.Am. J. Physiol. Endocrinol. Metab. 2007; 293: E1482-E1491Crossref PubMed Scopus (44) Google Scholar). Circulating ASP levels tend not to change during a fatty meal (13Charlesworth J.A. Peake P.W. Campbell L.V. Pussell B.A. O'Grady S. Tzilopoulos T. The influence of oral lipid loads on acylation stimulating protein (ASP) in healthy volunteers.Int. J. Obes. Relat. Metab. Disord. 1998; 22: 1096-1102Crossref PubMed Scopus (38) Google Scholar, 14Faraj M. Jones P. Sniderman A.D. Cianflone K. Enhanced dietary fat clearance in post-obese women.J. Lipid Res. 2001; 42: 571-580Abstract Full Text Full Text PDF PubMed Google Scholar); however, there is a postprandial increase in local adipose tissue ASP production (15Saleh J. Summers L.K.M. Cianflone K. Fielding B.A. Sniderman A.D. Frayn K.N. Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period.J. Lipid Res. 1998; 39: 884-891Abstract Full Text Full Text PDF PubMed Google Scholar, 16Kalant D. Phelis S. Fielding B.A. Frayn K.N. Cianflone K. Sniderman A.D. Increased postprandial fatty acid trapping in subcutaneous adipose tissue in obese women.J. Lipid Res. 2000; 41: 1963-1968Abstract Full Text Full Text PDF PubMed Google Scholar). While little is known regarding ASP regulation, chylomicrons have been shown to directly increase production of ASP through increased production of C3 and increased conversion of C3 to ASP in adipocytes (17Maslowska M. Scantlebury T. Germinario R. Cianflone K. Acute in vitro production of ASP in differentiated adipocytes.J. Lipid Res. 1997; 38: 1-11Abstract Full Text PDF PubMed Google Scholar, 18Scantlebury T. Maslowska M. Cianflone K. Chylomicron specific enhancement of Acylation Stimulating Protein (ASP) and precursor protein C3 production in differentiated human adipocytes.J. Biol. Chem. 1998; 273: 20903-20909Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar). Furthermore, previous studies on postprandial TG clearance in normal healthy subjects indicated that fasting ASP positively correlates with TG area under the curve (AUC), where higher ASP levels are associated with inefficient TG clearance (19Cianflone K. Zakarian R. Couillard C. Delplanque B. Despres J.P. Sniderman A.D. Fasting acylation stimulating protein is predictive of postprandial triglyceride clearance.J. Lipid Res. 2004; 45: 124-131Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar). Since ASP plays a pivotal role in dietary fatty acid uptake and esterification through modulation of LPL activity, we evaluated the impact of total and partial LPL deficiency on ASP levels and the association with lipid levels. Homozygote mutations in the LPL gene are rare autosomal recessive disorders with prevalence in the general population of approximately one in a million (20Evans V. Kastelein J.J. Lipoprotein lipase deficiency—rare or common?.Cardiovasc. Drugs Ther. 2002; 16: 283-287Crossref PubMed Scopus (20) Google Scholar). However two LPL mutations, G188E and P207L, that cause complete loss of postheparin LPL activity in homozygotes and 50% loss in heterozygotes, are commonly seen in Quebec, Canada (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar). The present study examines the plasma ASP levels in total or partial LPL-deficient patients in the fasting state and after a fatty meal (heterozygotes only). In addition, plasma ASP was measured in hypertriglyceridemic LPL heterozygotes before and following 3 months of fibrate treatment intended to TG levels. healthy from and were from the general control (CTL) with a of and lipid treatment were with a of without LPL deficiency triglyceride levels with or without were from the in as as the Lipid Lipid total of LPL homozygotes and LPL heterozygotes were also from the and the Lipid the of no was lipid or known to impact The was by local the and Lipid and was from The of subjects displayed a mutation P207L or G188E of the LPL gene In the had a mutation P207L, 3 had both P207L and G188E mutations, subjects had mutations, one and P207L, and the and while had an mutations have been shown to a in LPL postheparin activity (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar). While the mutation is known to cause a loss in LPL activity (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar), in with mutations, enzyme activity can and the subjects were to measured LPL In the had a mutation P207L of the LPL and subjects had mutations, one and P207L, and one P207L and mutations were known to cause a with a 50% loss in postheparin LPL activity (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar). The mutations were by as C. S. J. J. Gagne C. Julien P. in the a to Biophys. Res. PubMed Scopus Google Scholar). The heterozygotes were two heterozygotes with normal fasting TG and heterozygotes with high fasting TG were for and TG levels to the LPL heterozygotes, while subjects were for and to LPL In addition, heterozygotes were with for 3 LPL mutations for and and and and and heterozygotes with high fasting heterozygotes with normal fasting homozygotes. in a heterozygotes with high fasting heterozygotes with normal fasting homozygotes. a were in was by for levels in plasma and in lipoprotein and plasma triglyceride levels were measured by the were measured by an the NEFA was an from was by and the was after of in the with and as B. Gagne C. Julien P. in lipid and in lipoprotein lipase Biophys. Acta. PubMed Scopus Google Scholar). and as as were measured by with the by B. J. S. D. A. A. C. Despres J.P. The of the gene as a of the state in 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). was as by et D. K. Y. J. Julien P. P. T.J. D. Effect of receptor and lipoprotein lipase gene mutations on the of to lipid and hypertriglyceridemic 2002; PubMed Scopus (64) Google Scholar). ASP was measured as by M. H. Phelis S. Sniderman A.D. D. Cianflone K. acylation stimulating adipsin and lipids in and obese J. PubMed Scopus Google Scholar). and glucose levels were as indicated P. D. Gagne C. Despres J.P. A. and the of in lipoprotein lipase 1997; PubMed Scopus (38) Google Scholar). an the subjects were a The meal of a and of as a source of and two The was and to in the to the the of the subjects were to complete the The total were from from and from were taken and after the are expressed as of the Fasting TG, HDL-cholesterol and ASP and homozygotes were by fasting were by by versus in were by and postprandial were by by and are in was by Fasting and treatment were by and postprandial were by by where treatment and are in for and heterozygotes with hypertriglyceridemic subjects were by by of were by for subjects that were administered a fatload and were with and was P and of LPL-deficient subjects were a of LPL homozygotes LPL heterozygotes with normal fasting TG and LPL heterozygotes with high fasting TG shown in a of the LPL mutation were with the P207L or G188E mutations to both which are known to cause a (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar). In to LPL mutations, a homozygotes and heterozygotes also were for while control subjects were with the for and LPL-deficient < 3 subjects with subjects with heterozygotes with high fasting heterozygotes with normal fasting not are as were by by were by P < P < P < 3 subjects with subjects with in a heterozygotes with high fasting heterozygotes with normal fasting not are as were by by were by P < P < P < Increased TG and HDL-cholesterol levels are of LPL deficiency (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar). and female LPL homozygotes displayed a < 0.0001) and < 0.0001), increase in fasting TG levels with control HDL-cholesterol was reduced by < 0.0001) in male and by < 0.0001) in female LPL subjects with the control subjects In addition, total was increased by < in and < in plasma ASP levels were elevated in both male P < and female P < homozygotes subjects were and to heterozygotes with normal fasting TG similar TG both male and female displayed reduced HDL-cholesterol and P < Furthermore, with a fatty postprandial TG was for both male P < 0.0001) and female subjects P < 0.0001) with control as by increased NEFA levels were delayed in the male displayed postprandial and P < and to K. Xia Z. Chen L.Y. Critical review of Acylation Stimulating Protein physiology in humans and rodents.Biochim. Biophys. Acta. 2003; 1609: 127-143Crossref PubMed Scopus (314) Google Scholar), ASP levels not after the fat however postprandial ASP levels were higher in the male and female subjects versus control subjects While fasting ASP levels were higher in male P < and higher in female P < fasting insulin levels were in male heterozygotes and P < and female heterozygotes and P < fasting glucose levels were similar the two and and subjects with no known LPL mutation were and to LPL heterozygotes While total and were similar the HDL-cholesterol was in hypertriglyceridemic subjects the heterozygotes displayed elevated fasting TG levels with hypertriglyceridemic subjects and and P no in ASP levels was and P and and High-TG heterozygotes were on treatment for are commonly used as to TG levels and lipid the treatment reduced fasting TG, and and increased levels in both male and female female were male versus P < with female heterozygotes displayed reduced fasting NEFA and ASP levels following treatment while levels were heterozygotes had an increase in levels Furthermore, fibrate treatment had no effect on or insulin levels in male or female subjects of LPL subjects and ASP, acylation stimulating NEFA, nonesterified fatty TG, are as were by P < < P in a ASP, acylation stimulating NEFA, nonesterified fatty TG, are as were by P < < P In to fasting TG the fibrate treatment in male reduced postprandial TG NEFA and ASP The treatment had no effect on postprandial insulin or glucose were for female where fibrate treatment decreased postprandial TG NEFA and ASP no in postprandial insulin or glucose was following LPL heterozygotes postprandial before and after a fibrate treatment. Triglyceride NEFA ASP insulin and glucose levels following a fat Postprandial before and after a fibrate treatment in LPL was by where treatment and are indicated in are as where P < P < P < and is of the were in with treatment with subjects with no known LPL TG for male subjects was reduced by versus male < In after the fibrate TG was decreased with ASP was decreased in heterozygotes with hypertriglyceridemic subjects NEFA was for both male and with male subjects NEFA for female was decreased with female subjects was in both and with while glucose was not the and In addition, no was in for insulin or glucose and postprandial from control and LPL heterozygotes and were fasting ASP levels with NEFA in both and Fasting ASP also with P in and glucose P in Increased fasting TG and HDL-cholesterol are to as the of LPL deficiency (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google Scholar); is of total deficiency not for partial In the present study we two of LPL heterozygotes, one with normal and one with high fasting the heterozygotes had HDL-cholesterol levels with control while the TG heterozygotes displayed a in HDL-cholesterol with control subjects. While are the is and the for in LPL is of fasting TG we that both LPL heterozygotes displayed delayed postprandial clearance coupled with high ASP levels. The G188E and the mutations both have been shown to cause delayed postprandial TG clearance M. P. H. clearance of postprandial in of LPL gene Lipid Res. 40: Full Text Full Text PDF PubMed Google C. R.M. V. J. O. Lipoprotein lipase and are associated with increased plasma triglyceride and lipoprotein studies in the fasting and postprandial the 1997; PubMed Scopus Google Scholar, Gagne H. mutation in the lipoprotein lipase gene in postprandial triglyceride and in Lipid Res. 1996; Full Text PDF PubMed Google Scholar), and the mutation is by postprandial clearance B. B. B. lipoprotein lipase deficiency to a mutation as the cause of triglyceride with lipoprotein PubMed Scopus Google Scholar, J. Kastelein J.J. J.A. Lipoprotein lipase a Biol. 26: PubMed Scopus Google Scholar). one evaluated postprandial lipids in the P207L mutation M. D. M. clearance in 1991; PubMed Scopus Google Scholar), a common mutation in (1Murthy V. Julien P. Gagne C. Molecular pathobiology of the human lipoprotein lipase gene.Pharmacol. Ther. 1996; 70: 101-135Crossref PubMed Scopus (159) Google and the mutation in the LPL-deficient subjects Furthermore, in the present study we that both LPL homozygotes and heterozygotes increased fasting ASP levels. ASP levels are elevated in patients with disorders as and M. H. Phelis S. Sniderman A.D. D. Cianflone K. acylation stimulating adipsin and lipids in and obese J. PubMed Scopus Google Scholar, K. Jr., J. Sniderman A.D. acylation stimulating protein in Biol. 1997; PubMed Google Y. Lu J. Cianflone K. acylation stimulating and complement C3 in obese J. Obes. PubMed Scopus Google Scholar, H. Y. M. Lu H. J. H. Cianflone K. influence on acylation stimulating protein (ASP) and complement C3 in and Metab. PubMed Scopus Google Scholar, Y. J. Y. H. M. Cianflone K. Increased and lipid levels in with Full Text Full Text PDF PubMed Scopus Google Scholar). of disorders are also associated with In increased plasma ASP is to and increased ASP can be increased in the of as in Y. Lu J. Cianflone K. acylation stimulating and complement C3 in obese J. Obes. PubMed Scopus Google Scholar), Y. J. Y. H. M. Cianflone K. Increased and lipid levels in with Full Text Full Text PDF PubMed Scopus Google and as in in LPL Furthermore, LPL-deficient subjects normal and TG Gagne C. Julien P. A. S. C. lipoprotein lipase activity study of total and subcutaneous fat tissue 38: Full Text PDF PubMed Scopus Google Scholar, Despres J.P. T. Gagne C. Julien P. and in lipoprotein lipase J. Obes. Relat. Metab. Disord. 16: Google Scholar). the increased ASP seen in LPL deficiency is not associated with elevated insulin levels. In the LPL heterozygotes to be insulin control and hypertriglyceridemic subjects. In addition, have reduced plasma glucose and increased insulin in LPL-deficient subjects during an oral glucose with J. H. J. K. Y. Y. A. T. insulin in patients with lipoprotein lipase deficiency and Res. Full Text Full Text PDF PubMed Scopus Google Scholar). The of associated with LPL deficiency homozygotes and LPL in the elevated levels of studies have shown that chylomicrons stimulate the and production of both ASP and its precursor protein C3 (17Maslowska M. Scantlebury T. Germinario R. Cianflone K. Acute in vitro production of ASP in differentiated adipocytes.J. Lipid Res. 1997; 38: 1-11Abstract Full Text PDF PubMed Google Scholar, 18Scantlebury T. Maslowska M. Cianflone K. Chylomicron specific enhancement of Acylation Stimulating Protein (ASP) and precursor protein C3 production in differentiated human adipocytes.J. Biol. Chem. 1998; 273: 20903-20909Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, T. T. T. A. Y. K. Chylomicron C3 by the role of to of acylation stimulating protein.J. 2007; PubMed Scopus Google Scholar). fasting TG and NEFA were not increased in LPL heterozygotes, postprandial TG and NEFA clearance were and ASP levels remained Furthermore, fasting ASP positively with NEFA high ASP is associated with delayed NEFA clearance. While high plasma ASP is associated with disorders (as the of elevated ASP levels are In vitro studies in adipocytes have shown that ASP stimulates in situ LPL activity by increasing FA uptake and relieving product inhibition (8Faraj M. Sniderman A.D. Cianflone K. ASP enhances in situ lipoprotein lipase activity by increasing fatty acid trapping in adipocytes.J. Lipid Res. 2004; 45: 657-666Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, M. Cianflone K. Differential regulation of fatty acid trapping in mice adipose tissue and muscle by ASP.Am. J. Physiol. Endocrinol. Metab. 2004; 287: E150-E159Crossref PubMed Scopus (35) Google Scholar). the ASP plays an inhibitory role in muscle LPL activity was decreased by in muscle ASP (11Faraj M. Cianflone K. Differential regulation of fatty acid trapping in mice adipose tissue and muscle by ASP.Am. J. Physiol. Endocrinol. Metab. 2004; 287: E150-E159Crossref PubMed Scopus (35) Google Scholar). high ASP levels to delayed postprandial or the increased ASP is a of the effect on ASP to be the treatment for caused by a on and of in of the of the on and of in 2001; PubMed Scopus Google Scholar), are receptor is highly expressed in the muscle, and and the of involved in lipid including the of LPL In addition, which acts as a of LPL activity C. M. S. and Biophys. Acta. 2007; PubMed Scopus Google Scholar). The by which is however, an been shown to be by C. M. S. and Biophys. Acta. 2007; PubMed Scopus Google Scholar). can increase the activity of the in LPL heterozygotes, LPL activity and enhancing clearance from female heterozygotes from fibrate fasting TG by with male be by a the were had a higher higher ASP, and the in both and the fibrate treatment TG, and total levels in LPL heterozygotes, a in which are of the total lipoprotein tend to be elevated in LPL-deficient subjects S. A. B. R. B. and are increased in lipoprotein lipase 2003; PubMed Scopus Google Scholar). In addition, ASP levels were reduced during the Since the treatment resulted in TG and NEFA fibrate treatment in decreased ASP however, is to In to the on the is also expressed in adipose tissue, to a O. C. M. W. Differential of tissue of and in the 1996; PubMed Scopus Google Scholar). treatment on and TNF-α and were with treatment A. M. R.M. T. M. levels of and increases fatty acid in of 2001; PubMed Scopus Google Scholar, J. and of Acta. 2004; PubMed Scopus Google Scholar), while and both insulin hormones, were increased A. A. M. M. D. Z. T. K. et of receptor and on Biol. 2007; PubMed Scopus Google Scholar, J.A. Effect of and on the of and in fat of Biophys. Res. 2005; PubMed Scopus Google Scholar). ASP is an adipose tissue derived fibrate treatment its production and the of its receptor however to be In ASP is an hormone involved in stimulating NEFA esterification and TG glucose and activity in adipose tissue K. Xia Z. Chen L.Y. Critical review of Acylation Stimulating Protein physiology in humans and rodents.Biochim. Biophys. Acta. 2003; 1609: 127-143Crossref PubMed Scopus (314) Google Scholar), while on muscle LPL In LPL-deficient ASP levels are postprandial lipids are and ASP levels positively with NEFA In addition, fibrate treatment to both fasting and postprandial TG levels resulted in decreased ASP levels. The to Deshaies for and and

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