Relationship of Lipoprotein Lipase and Hepatic Triacylglycerol Lipase Activity to Serum Adiponectin Levels in Japanese Hyperlipidemic Men

Abstract

Objective: The aim of this study was to determine how lipoprotein lipase (LPL) and hepatic triacylglycerol lipase (HTGL) activity relate to serum adiponectin levels. Research design and methods: Fifty-five hyperlipidemic Japanese men were recruited for this study. LPL and HTGL activity in post-heparin plasma (PHP) was measured using Triton X-100 emulsified-[¹⁴C] triolein. The remaining activity in the presence of 1M NaCl was defined as HTGL activity. Serum adiponectin levels were determined by an enzyme-linked immunosorbent assay system. Result: LPL activity had a positive relationship with HDL₂, but had no relation with HDL₃, while HTGL had positive relationship with HDL₃, but had no relationship with HDL₂. LPL activity showed a positive relationship [r = 0.345, p = 0.010] to serum adiponectin levels, while and HTGL activity showed an inverse relationship [r = - 0.365 p = 0.006]. Multiple regression analysis with LPL and HTGL as dependent variables and age, BMI, serum adiponectin and the homeostasis model assessment of insulin resistance (HOMA-IR) as independent variables showed LPL and HTGL’s association to adiponectin did not persist after adjustments for these covariants. However, the association of LPL activity to HOMA-IR was found to persist after adjustments of age, BMI, and serum adiponectin. Conclusions: There was a co-linearity between insulin sensitivity and adiponectin as well as insulin sensitivity and LPL/HTGL activity.

Adiponectin · Hepatic triacylglycerol lipase · Lipoprotein lipase

References

• 1 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue.  Nature. 1994;  372 425-432
• 2 Hotamisligil G S, Shargill N S, Spiegelman B M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.  Science. 1993;  259 87-91
• 3 Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity.  Nat Med. 1996;  2 800-803
• 4 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1.  Biochem Biophys Res Commun. 1996;  221 286-289
• 5 Brunzell J D, Deeb S S. 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
• 6 Jackson R L. Lipoprotein lipase and hepatic lipase. In: Boyer PD (ed) Lipid Enzymology. Vol 16, The Enzymes. 3rd edition. New York; Academic Press 1983: 141-181
• 7 Nilsson-Ehle P, Garfinkel A S, Schotz M C. Lipolytic enzymes and plasma lipoprotein metabolism.  Ann Rev Biochem. 1980;  49 667-693
• 8 Hu E, Liang P, Spiegelman B M. AdipoQ is a novel adipocyte-specific gene dysregulated in obesity.  J Biol Chem. 1996;  271 10 697-10 703
• 9 Scherer P E, Williams S, Fogliano M, Baldini G, Lodish H F. A novel serum protein similar to C1q, produced exclusively in adipocytes.  J Biol Chem. 1995;  270 26 746-26 749
• 10 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1.  Biochem Biophys Res Commun. 1996;  221 286-289
• 11 Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn B B, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.  Nat Med. 2002;  8 1288-1295
• 12 Goldfine A B, Kahn C R. Adiponectin: linking the fat cell to insulin sensitivity.  Lancet. 2003;  362 1431-1432
• 13 Jansson P A, Pellme F, Hammarstedt A, Sandqvist M, Brekke H, Caidahl K, Forsberg M, Volkmann R, Carvalho E, Funahashi T, Matsuzawa Y, Wiklund O, Yang X, Taskinen M R, Smith U. A novel cellular marker of insulin resistance and early atherosclerosis in humans is related to impaired fat cell differentiation and low adiponectin.  FASEB J. 2003;  17 1434-1440
• 14 Katsuki A, Sumida Y, Urakawa H, Gabazza E C, Murashima S, Matsumoto K, Nakatani K, Yano Y, Adachi Y. Plasma levels of adiponectin are associated with insulin resistance and serum levels of triglyceride in Japanese metabolically obese, normal-weight men with normal glucose tolerance.  Diabetes Care. 2003;  26 2964-2965
• 15 Kern P A, di Gregorio G B, Lu T, Rassouli N, Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression.  Diabetes. 2003;  52 1779-1785
• 16 Cnop M, Havel P J, Utzschneider K M, Carr D B, Sinha M K, Boyko E J, Retzlaff B M, Knopp R H, Brunzell J D, Kahn S E. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex.  Diabetologia. 2003;  46 459-469
• 17 Ezenwaka C E, Kalloo R, Uhlig M, Eckel J. Relationship between adiponectin and metabolic variables in Caribbean offspring of patients with type 2 diabetes mellitus.  Horm Metab Res.. 2004;  36 238-242
• 18 Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.  Arterioscler Thromb Vasc Biol. 2000;  20 1595-1599
• 19 Pellme F, Smith U, Funahashi T, Matsuzawa Y, Brekke H, Wiklund O, Taskinen M R, Jansson P A. Circulating adiponectin levels are reduced in nonobese but insulin-resistant first-degree relatives of type 2 diabetic patients.  Diabetes. 2003;  52 1182-1186
• 20 Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin.  Circulation. 1999;  100 2473-2476
• 21 The Expert Committee on the diagnosis and classification of diabetes mellitus . Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.  Diabetes Care. 1997 Jul;  20 1183-1197
• 22 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
• 23 Kobayashi J, Shirai K, Saito Y, Yoshida S. Lipoprotein lipase with a defect in lipid interface recognition in a case with type I hyperlipidaemia.  Eur J Clin Invest. 1989;  19 424-432
• 24 Kobayashi J, Nishida T, Ameis D, Stahnke G, Schotz M C, Hashimoto H, Fukamachi I, Shirai K, Saito Y, Yoshida S. A heterozygous mutation (the codon for Ser447 → a stop codon) in lipoprotein lipase contributes to a defect in lipid interface recognition in a case with type I hyperlipidemia.  Biochem Biophys Res Commun. 1992;  182 70-77
• 25 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.  Biochem Biophys Res Commun. 1999;  257 79-83
• 26 Semencovich C F, Wims M, Noe L, Etienne J, Chan L. Insulin regulation of lipoprotein lipase activity in 3T3-L1 adipocytes is mediated at posttranscriptional and posttranslational levels.  J Biol Chem. 1989;  264 9030-9038
• 27 Ong J M, Kirchgessner T G, Schotz M C, Kern P A. Insulin increases the synthetic rate and messenger RNA level of lipoprotein lipase in isolated rat adipocytes.  J Biol Chem. 1988;  263 12 933-12 938
• 28 Eckel R H, Yost T J, Jensen D R. Alterations in lipoprotein lipase in insulin resistance.  Int J Obes Relat Metab Disord. 1995;  19 Suppl 1 S16-S21
• 29 Reynisdottir S, Angelin B, Langin D, Lithell H, Eriksson M, Holm C, Arner P. Adipose tissue lipoprotein lipase and hormone-sensitive lipase. Contrasting findings in familial combined hyperlipidemia and insulin resistance syndrome.  Arterioscler Thromb Vasc Biol. 1997;  17 2287-2292
• 30 Panarotto D, Remillard P, Bouffard L, Maheux P. Insulin resistance affects the regulation of lipoprotein lipase in the postprandial period and in an adipose tissue-specific manner.  Eur J Clin Invest. 2002;  32 84-92
• 31 Rashid S, Watanabe T, Sakaue T, Lewis G F. Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity.  Clin Biochem. 2003;  36 421-429
• 32 Baynes C, Henderson A D, Anyaoku V, Richmond W, Hughes C L, Johnston D G, Elkeles R S. The role of insulin insensitivity and hepatic lipase in the dyslipidaemia of type 2 diabetes.  Diabet Med. 1991;  8 560-566
• 33 Riemens S C, van Tol A, Scheek L M, Dullaart R P. Plasma cholesteryl ester transfer and hepatic lipase activity are related to high-density lipoprotein cholesterol in association with insulin resistance in type 2 diabetic and non-diabetic subjects.  Scand J Clin Lab Invest. 2001;  61 1-9
• 34 von Eynatten M, Schneider J G, Humpert P M, Rudofsky G, Schmidt N, Barosch P, Hamann A, Morcos M, Kreuzer J, Bierhaus A, Nawroth P P, Dugi K A. Decreased plasma lipoprotein lipase in hypoadiponectinemia: an association independent of systemic inflammation and insulin resistance.  Diabetes Care.. 2004;  27 2925-2929