The Relationship of Serum Lipoprotein Lipase Mass with Fasting Serum Apolipoprotein B-48 and Remnant-like Particle Triglycerides in Type 2 Diabetic Patients

Abstract

Background: There have been no previous reports showing specifically the relation between lipoprotein lipase (LPL) and apolipoprotein (apo) B-48 or remnant metabolism. In this study, we have clarified the relationships of LPL mass in pre-heparin with serum apo B-48 measured by enzyme-linked immunosorbent assay, triglycerides (TG), and remnant-like particle triglycerides (RLP-TG).

Material and Methods: Seventy-nine type 2 diabetic subjects [age, 55±13; body mass index (BMI), 25±5.0 kg/m²; fasting plasma glucose (FPG), 7.39±2.22 mmol/l, HbA1c, 6.5±1.3%, total cholesterol (TC), 5.36±1.09 mmol/l, TG, 2.32±2.53 mmol/l; HDL-C, 1.22±0.44 mmol/l; serum LPL mass, 45±22 ng/ml; apo B-48, 6.6±6.3 μg/ml] were recruited in this study. Fasting serum apo B-48 were measured by ELISA using anti-human apo B-48 monoclonal antibodies (MoAb) and LPL mass by ELISA using anti-bovine milk LPL MoAb. RLP-TG levels were measured using monoclonal antibodies to apo B-100 and apo A-1.

Results: There was no relationship of LPL mass to age, BMI, FPG, and HbA1c. Serum LPL mass was correlated inversely with TG (r=-0.529 p<0.0001) and positively with HDL-C (r=0.576, p<0.0001). Also, LPL mass showed inverse correlations with apo B-48 (r=-0.383 p<0.0001) and RLP-TG (r=-0.422 p<0.0001, n=51). Multiple regression analysis with TG, apo B-48, or RLP-TG as dependent variables, and age, gender, BMI, plasma glucose, and LPL mass as independent variables showed that LPL mass was associated independently with TG, apo B-48, or RLP-TG.

Conclusion: The decrease in LPL protein mass could cause an increase in serum apo B-48 and RLP-TG levels, which is related to the retardation of remnant metabolism.

Chylomicrons - ELISA - plasma glucose - body mass index - HDL-cholesterol

References

• 1 Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies.  J Cardiovasc Risk. 1996;  3 213-219
• 2 Patsch JR, Miesenbock G, Hopferwieser T, Muhlberger V, Knapp E, Dunn JD, Gotto Jr AM, Patsch W. Relation of triglyceride metabolism and coronary artery disease.  Arterioscler Thromb. 1992;  12 1336-1345
• 3 Zilversmit DB. Atherogenic nature of triglycerides, postprandial lipidemia, and triglyceride-rich remnant lipoproteins.  Clin Chem. 1995;  41 153-158
• 4 Miensenbock G, Patsch JR. Postprandial hyperlipidemia: the search for the atherogenic lipoprotein.  Curr Opin Lipidol. 1992;  3 196-201
• 5 Havel R J. Postprandial hyperlipidemia and remnant lipoproteins.  Curr Opin Lipidol. 1994;  5 102-119
• 6 Karpe F, Hamsten A. Postprandial lipoprotein metabolism and atherosclerosis.  Curr Opin Lipidol. 1995;  6 123-129
• 7 Zilversmit DB. Atherogenesis: a postprandial phenomenon.  Circulation. 1979;  60 473-485
• 8 Havel RJ, Kane JP, Kashyap ML. Interchange of apolipoproteins between chylomicrons and high-density lipoproteins during alimentary lipemia in man.  J Clin Invest. 1973;  52 32-38
• 9 Nilsson-Ehle P, Garfinkel AS, Schotz MC. Lipolytic enzymes and plasma lipoprotein metabolism.  Ann Rev Biochem. 1980;  49 667-693
• 10 Brunzell JD, Deeb SS. Familial lipoprotein lipase deficiency, apo C-II deficiency and hepatic lipase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D. (eds). The metabolic and molecular basis of inherited disease. New York: Mc Graw-Hill Inc. 2001: 2789-2816
• 11 Kobayashi J, Saito K, Fukamachi I, Taira K, Takahashi K, Bujo H, Saito Y. Pre-heparin plasma lipoprotein lipase mass: Its correlation with intra-abdominal visceral fat accumulation.  Horm Metab Res. 2001;  33 412-416
• 12 Miyashita Y, Shirai K, Itoh Y, Sasaki H, Totsuka M, Murano T, Watanabe H. Low lipoprotein lipase mass in preheparin serum of type 2 diabetes mellitus patients and its recovery with insulin therapy.  Diabetes Res Clin Pract. 2002;  56 181-187
• 13 Kobayashi J, Maruyama T, Watanabe H, Kudoh A, Tateishi S, Sasaki T, Murano S, Watanabe M. Gender differences in the effect of type 2 diabetes on serum lipids, pre-heparin plasma lipoprotein lipase mass and other metabolic parameters in Japanese population.  Diabetes Res Clin Pract. 2003;  62 39-45
• 14 Kobayashi J. Pre-heparin lipoprotein lipase mass.  J Atheroscler Thromb. 2004;  11 1-5
• 15 Kobayashi J, Tateishi S, Maruyama T, Kudoh A, Murano S. Marked reduction in serum high-density lipoprotein cholesterol levels in a woman with acute inflammation due to diabetic gangrene.  Clin Chim Acta. 2003;  335 33-38
• 16 Hanyu O, Miida T, Obayashi K, Ikarashi T, Soda S, Kaneko S, Hirayama S, Suzuki K, Nakamura Y, Yamatani K, Aizawa Y. Lipoprotein lipase (LPL) mass in preheparin serum reflects insulin sensitivity.  Atherosclerosis. 2004;  174 385-390
• 17 Rip J, Nierman MC, Wareham NJ, Luben R, Bingham SA, Day NE, Miert JN van, Hutten BA, Kastelein JJ, Kuivenhoven JA, Khaw KT, Boekholdt SM. Serum lipoprotein lipase concentration and risk for future coronary artery disease: the EPIC-Norfolk prospective population study.  Arterioscler Thromb Vasc Biol. 2006;  26 637-642
• 18 Khaw KT, Bingham S, Welch A, Luben R, Wareham N, Oakes S, Day N. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition.  Lancet. 2001;  357 657-663
• 19 ChanL, Chang BH, Nakamuta M, Li WH, Smith LC. Apobec-1 and apolipoprotein B mRNA editing.  Biochim Biophys Acta. 1997;  1345 11-26
• 20 Davidson NO, Shelness GS. Apolipoprotein B: mRNA editing, lipoprotein assembly, and presecretory degradation.  Annu Rev Nutr. 2000;  20 169-193
• 21 Sakai N, Uchida Y, Ohashi K, Hibuse T, Saika Y, Tomari Y, Kihara S, Hiraoka H, Nakamura T, Ito S, Yamashita S, Matsuzawa Y. Measurement of fasting serum apoB-48 levels in normolipidemic and hyperlipidemic subjects by ELISA.  J Lipid Res. 2003;  44 1256-1262
• 22 Nakajima K, Okazaki M, Tanaka A. et al . Separation and determination of remnant-like particles in human serum using monoclonal antibodies to apo B-100 and apo A-1.  J Clin Ligand Assay. 1996;  19 177-183
• 23 Cohn JS, Marcoux C, Davignon J. Detection, quantification and characterization of potential atherogenic triglyceride-rich remnant lipoproteins.  Arterioscler Thromb Vasc Biol. 1999;  19 2474-2486
• 24 Campos E, Nakajima K, Tanaka A, Havel RJ. Properties of an apolipoprotein E-enriched fraction of triglyceride-rich lipoproteins isolated from human blood plasma with a monoclonal antibody to apolipoprotein B-100.  J Lipid Res. 1992;  33 369-380
• 25 Weintraub MS, Eisenberg S, Breslow JL. Different patterns of postprandial lipoprotein metabolism in normal, type IIa, type III, and type IV hyperlipoproteinemic individuals. Effects of treatment with cholestyramine and gemfibrozil.  J Clin Invest. 1987;  79 1110-1119
• 26 Mero N, Malmstrom R, Steiner G, Taskinen MR, Syvanne M. Postprandial metabolism of apolipoprotein B-48- and B-100-containing particles in type 2 diabetes mellitus: relations to angiographically verified severity of coronary artery disease.  Atherosclerosis. 2000;  150 167-177
• 27 Phillips C, Murugasu G, Owens D, Collins P, Johnson A, Tomkin GH. Improved metabolic control reduces the number of postprandial apolipoprotein B-48-containing particles in type 2 diabetes.  Atherosclerosis. 2000;  148 283-291
• 28 Guo Q, Avramoglu RK, Adeli K. Intestinal assembly and secretion of highly dense/lipid-poor apolipoprotein B48-containing lipoprotein particles in the fasting state: evidence for induction by insulin resistance and exogenous fatty acids.  Metabolism. 2005;  54 689-697
• 29 Kobayashi J, Nohara A, Kawashiri MA, Inazu A, Koizumi J, Nakajima K, Mabuchi H. Serum lipoprotein lipase mass: Clinical significance of its measurement.  Clin Chim Acta. 2007;  378 7-12
• 30 Auwerx JH, Babirak SP, Fujimoto WY, Iverius PH, Brunzell JD. Defective enzyme protein in lipoprotein lipase deficiency.  Eur J Clin Invest. 1989;  19 433-437
• 31 Kern PA, Martin RA, Carty J, Goldberg IJ, Ong JM. Identification of lipoprotein lipase immunoreactive protein in pre- and postheparin plasma from normal subjects and patients with type I hyperlipoproteinemia.  J Lipid Res. 1990;  31 17-26
• 32 Tornvall P, Olivecrona G, Karpe F, Hamsten A, Olivecrona T. Lipoprotein lipase mass and activity in plasma and their increase after heparin injection.  Arterioscler Thromb Vasc Biol. 1995;  15 1086-1093
• 33 Tornvall P, Karpe F, Proudler A, Bavenholm P, Landou C, Olivecrona T, Hamsten A. High-density lipoprotein: Relations to metabolic parameters and severity of coronary artery disease.  Metabolism. 1996;  45 1375-1382
• 34 Hitsumoto T, Ohsawa H, Uchi T, Noike H, Kanai M, Yoshinuma M, Miyashita Y, Watanabe H, Shirai K. Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis.  Atherosclerosis. 2000;  153 391-396
• 35 Hitsumoto T, Yoshinaga K, Aoyagi K, Sakurai T, Kanai M, Uchi T, Noike H, Ohsawa H, Watanabe H, Shirai K. Association between preheparin serim lipoprotein lipase mass and acute myocardial infarction in Japanese men.  J Atheroscler Thromb. 2002;  9 163-169
• 36 Watanabe H, Miyashita Y, Murano T, Hiroh Y, Itoh Y, Shirai K. Preheparin serum lipoprotein lipase mass level: The effects of age, gender and type of hyperlipidemia.  Atherosclerosis. 1999;  145 45-50
• 37 Hirano T, Nishioka F, Murakami T. Measurement of the serum lipoprotein lipase concentration is useful for studying triglyceride metabolism: Comparison with postheparin plasma.  Metabolism. 2004;  53 526-531
• 38 Saiki A, Oyama T, Endo K, Ebisuno M, Ohira M, Koide N, Murano T, Miyashita , Shirai K. Preheparin serum lipoprotein lipase mass might be a biomarker of metabolic syndrome.  Diabetes Res Clin Pract. 2006;  , Sep 4; [Epub ahead of print]
• 39 Kobayashi J, Kusunoki M, Murase Y, Kawashiri M, Higashikata T, Miwa K, Katsuda S, Takata M, Asano A, Nohara A, Inazu A, Mabuchi H. Relationship of lipoprotein lipase and hepatic triacylglycerol lipase activity to serum adiponectin levels in Japanese hyperlipidemic men.  Horm Metab Res. 2005;  37 505-509
• 40 Williams KJ, Fless GM, Petrie KA, Snyder ML, Brocia RW, Swenson TL. Mechanism by which lipoprotein lipase alters cellular metabolism of lipoprotein (a), low density lipoprotein, and nascent lipoproteins: Roles for low density lipoprotein receptors and heparan sulphate proteoglycans.  J Biol Chem. 1992;  267 13284-13292

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