Lipoprotein lipase and obesity

Abstract

Obesity is one of the fast-growing major diseases in developed and developing countries. As has been persuasively argued, long-term imbalance between intake and expenditure of fat is a central factor in the etiology of obesity. Obesity aggravates insulin resistance and promotes cardiovascular diseases and atherosclerosis. We hypothesized that elevating lipoprOtein lipase (LPL) activity in skeletal muscle would cause an improvement of obesity. To test this hypothesis, we studied the effects of the LPL activator NO-1886 inobese animals. NO-1886 elevated LPL activity in skeletal muscle, and improved obesity as well as insulin resistance in obese rats. Furthermore, NO-1886 mitigated body weight gain induced by pioglitazone without suppressive effect on the adiponectin-increasing action of pioglitazone. LPL activators hold a lot of promise of curing several diseases shown above in clinical scene.

Share and Cite:

Kusunoki, M. , Tsutsumi, K. , Sato, D. and Nakamura, T. (2012) Lipoprotein lipase and obesity. Health, 4, 1405-1412. doi: 10.4236/health.2012.412A203.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Spiegelman, B.M. and Flier, J.S. (1996) Adipogenesis and obesity: Rounding out the big picture. Cell, 87, 377-389. doi:10.1016/S0092-8674(00)81359-8
[2] Goldberg, I.J. (1996) Lipoprotein lipase and lipolysis: Central roles in lipoprotein metabolism and atherogenesis. Journal of Lipid Research, 37, 693-707.
[3] Hara, T., Cameron-Smith, D., Cooney, G.J., Kusunoki, M., Tsutsumi, K., et al. (1998) The actions of a novel lipoprotein lipase activator, NO-1886, in hypertriglyceridemic fructosefed rats. Metabolism, 47, 149-153. doi:10.1016/S0026-0495(98)90211-6
[4] Peterson, J., Fuji-moto, W.Y. and Brunzell, J.D. (1992) Relationship of activity, heparin affinity, and conformation as studied with monoclonal antibodies. Journal of Lipid Research, 33, 1165-1170.
[5] Sparkes, R.S., Zollman, S., Klisak, I., Kir-chgessner, T.G., Komaromy, M.C., et al. (1987) Human genes involved in lipolysis of plasma lipoproteins: Mapping of loci for lipoprotein lipase to 8p22 and hepatic lipase to 15q21. Genomics, 1, 138-144. doi:10.1016/0888-7543(87)90005-X
[6] Wion, K.L., Kir-chgessner, T.G., Lusis, A.J., Schotz, M.C. and Lawn, R.M. (1987) Human lipoprotein lipase complementary DNA sequence. Science, 235, 1638-1641. doi:10.1126/science.3823907
[7] Senda, M., Oka, K., Brown, W.V., Qasba, P.K. and Furuichi, Y. (1987) Molecular cloning and sequence of cDNA coding for bovine lipoprotein lipase. Proceedings of the National Academy of Sciences of the United States of America, 84, 4369-4373. doi:10.1073/pnas.84.13.4369
[8] Clarke, A.R., Luscombe, M. and Holbrook, J.J. (1983) The effect of the chain length of he-parin on its interaction with lipoprotein lipase. Biochimica et Biophysica Acta, 747, 130-137. doi:10.1016/0167-4838(83)90131-0
[9] Pedersen, M.E., Co-hen, M. and Schotz, M.C. (1983) Immunocytochemical localization of the functional fraction of lipoprotein lipase in the perfused heart. Journal of Lipid Research, 24, 512-521.
[10] Brunzell, J.D. (1995) Familial lipoprotein lipase deficiency and other causes of chylomicromia syndrome. In: Scriver, C.R., Baudette, A.L., Sly, W.S. and Valle, D., Eds., The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 1913-1932. doi:10.1016/S0307-4412(96)80019-7
[11] Nikkil?, E.A., Taskinen, M.R. and Kekki, M. (1978) Relation of plasma high-density lipoprotein cholesterol to lipoprotein-lipase activity in adipose tissue and skeletal muscle of man. Atherosclerosis, 29, 497-501.
[12] Kusunoki, M., Tsutsumi, K., Sato, D., Nakamura, A., Habu, S., et al. (2011). Activation of lipoprotein lipase increases serum high density lipoprotein 2 cholesterol and enlarges high density lipoprotein 2 particles in rats. European Journal of Pharmacology, 668, 337-339. doi:10.1016/j.ejphar.2011.06.040
[13] Tsutsumi, K., Inoue, Y., Shima, A., Iwasaki, K., Kawamura, M., et al. (1993) The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis. Journal of Clinical Investigation, 92, 411-417. doi:10.1172/JCI116582
[14] Raynolds, M.V., Awald, P.D., Gordon, D.F., Gutierrez- Hartmann, A., Rule, D.C., et al. (1990) Lipoprotein lipase gene expression in rat adipocytes is regulated by isoproterenol and insulin through different mechanisms. Molecular Endocrinology, 4, 1416-1422. doi:10.1210/mend-4-9-1416
[15] Tsutsumi, K., Inoue, Y., Shima, A. and Murase, T. (1995) Correction of hypertriglyceri-demia with low high-density lipoprotein cholesterol by the novel compound NO-1886, a lipoprotein lipase-promoting agent, in STZ-induced diabetes rats. Diabetes, 44, 414-417. doi:10.2337/diabetes.44.4.414
[16] Miesenb?ck, G., H?lzl, B., F?ger, B., Brandst?tter, E., Paulweber, B., et al. (1993) Hete-rozygous lipoprotein lipase deficiency due to a missense muta-tion as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities. Journal of Clinical Investigation, 91, 448-455. doi:10.1172/JCI116222
[17] Katzel, L.I., Busby-Whitehead, M.J., Rogus, E.M., Krauss, R.M. and Gold-berg, A.P. (1994) Reduced adipose tissue lipoprotein lipase responses, postprandial lipemia, and low high-density lipo-protein-2 subspecies levels in older athletes with silent myo-cardial ischemia. Metabo- lism, 43, 190-198. doi:10.1016/0026-0495(94)90244-5
[18] Reymer, P.W., Gagné, E., Groenemeyer, B.E., Zhang, H., Forsyth, I., et al. (1995) A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis. Nature Genetics, 10, 28-34. doi:10.1038/ng0595-28
[19] Gaziano, J.M., Hennekens, C.H., O’Donnell, C.J., Bres- low, J.L. and Buring, J.E. (1997) Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation, 96, 2520-2525. doi:10.1161/01.CIR.96.8.2520
[20] Fan, J., Unoki, H., Kojima, N., Sun, H., Shimoyamada, H., et al. (2001) Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholestero- lemia and atherosclerosis. The Journal of Biological Chemistry, 276, 40071-40079. doi:10.1074/jbc.M105456200
[21] Shimada, M., Shimano, H., Gotoda, T., Yamamoto, K., Kawamura, M., et al. (1993) Over-expression of human lipoprotein lipase in transgenic mice. Resistance to dietinduced hypertriglyceridemia and hyper-cholesterolemia. The Journal of Biological Chemistry, 268, 17924-17929.
[22] Shimada, M., Ishibashi, S., Inaba, T., Yagyu, H., Harada, K., et al. (1996) Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase. Proceedings of the National Academy of Sciences of the United States of America, 93, 7242-7246. doi:10.1073/pnas.93.14.7242
[23] Tsutsumi, K., Inoue, Y., Hagi, A. and Murase, T. (1997) The novel compound NO-1886 elevates plasma high- density lipoprotein cholesterol levels in hamsters and rabbits by increasing lipoprotein lipase without any effect on cholesteryl ester transfer protein activity. Metabolism, 46, 257-260. doi:10.1016/S0026-0495(97)90250-X
[24] Shimokawa, H. and Vanhoutte, P.M. (1989) Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arrteries in hypercholesterolemia and atherosclerosis. Circulation Research, 64, 900-914. doi:10.1161/01.RES.64.5.900
[25] Lakatta, E.G. and Yin, F.C. (1982) Myocardial aging: Functional alterations and related cellular mechanisms. The American Journal of Physiology, 242, H927-H941.
[26] Moritoki, H., Tanioka, A., Maeshiba, Y., Iwamoto, T., Ishida, Y., et al. (1988) Age-associated decrease in hista- mine-induced vasodilation may be due to reduction of cyclic GMP formation. British Journal of Pharmacology, 95, 1015-1022. doi:10.1111/j.1476-5381.1988.tb11734.x
[27] Hara, T., Kusunoki, M., Tsutsumi, K., Okada, K., Sakamoto, S., et al. (1998) A lipoprotein lipase activator, NO-1886, improves en-dothelium-dependent relaxation of rat aorta associated with aging. European Journal of Pharmacology, 350, 75-79. doi:10.1016/S0014-2999(98)00230-1
[28] Kusunoki, M., Tsutsumi, K., Hara, T., Ogawa, H., Nakamura, T., et al. (2002) A lipoprotein lipase activator, NO-1886 prevents impaired en-dothelium-dependent relaxation of aorta caused by exercise in aged rats. Experimental Gerontology, 37, 891-896. doi:10.1016/S0531-5565(02)00023-2
[29] Ohta, T., Takata, K., Horiuchi, S., Morino, Y. and Matsuda, I. (1989) Protective effect of lipoproteins containing apoprotein A-I on Cu2+-catalyzed oxidation of human low density lipoprotein. FEBS Letters, 257, 435-438. doi:10.1016/0014-5793(89)81590-X
[30] Chiba, T., Miura, S., Sawamura, F., Uetsuka, R., Tomita, I., et al. (1997) Antiathero-genic effects of a novel lipo- protein lipase-enhancing agent in cholesterol-fed New Zealand white rabbits. Atherosclerosis, Thrombosis, and Vascular Biology, 17, 2601-2608. doi:10.1161/01.ATV.17.11.2601
[31] Yin, W., Tsutsumi, K., Yuan, Z. and Yang, B. (2002) Ef- fects of the lipoprotein lipase activator NO-1886 as a suppressor agent of atherosclerosis in aorta of mild dia- betic rabbits. Arzneimittelforschung, 52, 610-614. doi:10.1055/s-0031-1299939
[32] White, R.T., Damm, D., Hancock, N., Rosen, B.S., Lowell, B.B., et al. (1992) Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. The Journal of Biological Chemi-stry, 267, 9210-9213.
[33] Friedman, J.M. (2000) Obesity in the new millennium. Nature, 404, 632-634. doi:10.1038/35017505
[34] Shimomura, I., Funahashi, T., Takahashi, M., Maeda, K., Kotani, K., et al. (1996) Enhanced expression of PAI-1 in visceral fat: Possible contributor to vascular disease in obesity. Nature Medicine, 2, 800-803. doi:10.1038/nm0796-800
[35] Steppan, C.M., Bailey, S.T., Bhat, S., Brown, E.J., Ban- erjee, R.R., et al. (2001) The hor-mone resistin links obesity to diabetes. Nature, 409, 307-312. doi:10.1038/35053000
[36] Hotamisligil, G.S. (1999) The role of TNFα and TNF receptors in obesity and insulin resistance. Journal of Internal Medicine, 245, 621-625. doi:10.1046/j.1365-2796.1999.00490.x
[37] Scherer, P.E., Williams, S., Fogliano, M., Baldini, G. and Lodish, H.F. (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. The Journal of Bio- logical Chemistry, 270, 26746-26749. doi:10.1074/jbc.270.45.26746
[38] Kern, P.A., Ong, J.M., Saffari, B. and Carty, J. (1990) The effect of weight loss on the activity and expression of adipose-tissue lipoprotein lipase in very obese humans. The New England Journal of Medicine, 322, 1053-1059. doi:10.1056/NEJM199004123221506
[39] Sadur, C.N., Yost, T.J. and Eckel, R.H. (1984) Insulin responsiveness of adipose tissue lipoprotein lipase is de- layed but preserved in obesity. The Journal of Clinical Endocrinology and Metabolism, 59, 1176-1182. doi:10.1210/jcem-59-6-1176
[40] Shimada, M., Ishibashi, S., Yamamoto, K., Kawamura, M., Watanabe, Y., et al. (1995) Overexpression of human lipoprotein lipase increases hor-mone-sensitive lipase activity in adipose tissue of mice. Bio-chemical and Bio- physical Research Communications, 211, 761-766. doi:10.1006/bbrc.1995.1878
[41] Jensen, D.R., Schlaepfer, I.R., Morin, C.L., Pennington, D.S., Marcell, T., et al. (1997) Prevention of diet-induced obesity in transgenic mice overex-pressing skeletal muscle lipoprotein lipase. The American Journal of Physiology, 273, R683-R689.
[42] Ferrano, R.T., Eckel, R.H., Larson, D.E., Fontvieille, A.M., Rising, R., et al. (1993) Relationship between ske- letal muscle lipoprotein lipase activity and 24-hour mac- ronutrient oxidation. The Journal of Clinical Investiga- tion, 92, 441-445. doi:10.1172/JCI116586
[43] Kusunoki, M., Hara, T., Tsutsumi, K., Nakamura, T., Miyata, T., et al. (2000) The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resis- tance in rats fed a high-fat diet. Diabetologia, 43, 875- 880. doi:10.1007/s001250051464
[44] Boss, O., Muzzin, P. and Giacobino, J.P. (1998) The un- coupling proteins, a re-view. European Journal of Endo- crinology, 139, 1-9. doi:10.1530/eje.0.1390001
[45] Schrauwen, P. and Hesselink, M. (2002) UCP2 and UCP3 in muscle controlling body meta-bolism. The Journal of Experimental Biology, 205, 2275-2285.
[46] Doi, M., Kondo, Y. and Tsutsumi, K. (2003) Lipoprotein lipase activator NO-1886 (ibrolipim) accelerates the mRNA expression of fatty acid oxidation-related enzymes in rat liver. Metabolism, 52, 1547-1550. doi:10.1016/j.metabol.2003.07.007
[47] Kusunoki, M., Tsut-sumi, K., Iwata, K., Yin, W., Nakamura, T., et al. (2005) NO-1886 (ibrolipim), a lipoprotein lipase activator, increases the expression of uncoupling protein 3 in skeletal muscle and suppresses fat accumula- tion in high-fat diet-induced obesity in rats. Metabolism, 54, 1587-1592. doi:10.1016/j.metabol.2005.06.005
[48] Spiegelman, B.M. (1998) PPAR-γ: Adipogenic regulator and thiazolidinedione receptor. Diabetes, 47, 507-514. doi:10.2337/diabetes.47.4.507
[49] Miyazaki, Y. and Defronzo, R.A. (2008) Rosiglitazone and pioglitazone similarly improve insulin sensitivity and secretion, glucose tolerance and adipo-cytokines in type 2 diabetic patients. Diabetes, Obesity & Me-tabolism, 10, 1204-1211. doi:10.1111/j.1463-1326.2008.00880.x
[50] Boden, G. and Zhang, M. (2006) Recent findings con- cerning thiazolidine-diones in the treatment of diabetes. Expert Opinion on Investi-gational Drugs, 15, 243-250. doi:10.1517/13543784.15.3.243
[51] Hermansen, K. and Mortensen, L.S. (2007) Bodyweight changes associated with antihyperglycemic agents in type 2 diabetes mellitus. Drug Safety, 30, 1127-1142. doi:10.2165/00002018-200730120-00005
[52] Hallakou, S., Doaré, L., Foufelle, F., Kerqoat, M., Guerre-Millo, M., et al. (1997) Pioglitazone induces in vitro adipocyte differentiation in the obese Zucker fa/fa rat. Diabetes, 46, 1393-1399. doi:10.2337/diabetes.46.9.1393
[53] Kusunoki, M., Tsutsumi, K., Sato, D., Nakamura, A., Habu, S., et al. (2011) Pioglita-zone-induced body weight gain is prevented by combined ad-ministration with the lipoprotein lipase activator NO-1886. European Journal of Pharmacology, 668, 486-491. doi:10.1016/j.ejphar.2011.07.030
[54] Kusunoki, M., Tsutsumi, K., Nakayama, M., Kurokawa, T., Nakamura, T., et al. (2007) Relationship between se- rum concentrations of saturated fatty acids and unsatu- rated fatty acids and the homeostasis model insulin resis- tance index in Japanese patients with type 2 di-abetes mel- litus. The Journal of Medical Investigation, 54, 243-247. doi:10.2152/jmi.54.243
[55] Sato, D., Nakamura, T., Tsutsumi, K., Shinzawa, G., Karimata, T., et al. (2012) Site dependency of fatty acid composition in adipose triacylglycerol in rats and its absence as a result of high-fat feeding. Metabolism, 61, 92-98. doi:10.1016/j.metabol.2011.05.012
[56] Matsuzaka, T., Shi-mano, H., Yahagi, N., Kato, T., Atsumi, A, et al. (2007) Crucial role of a long-chain fatty acid elongase, Elovl6, in obesi-ty-induced insulin resistance. Nature Medicine, 13, 1193-1202. doi:10.1038/nm1662

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.