Journal List > Endocrinol Metab > v.26(3) > 1085888

Jun, Ko, Jung, Yoon, Kim, Kwon, Lee, Suk, Kim, Kim, and Park: Effect of Omega-3 Fatty Acids on Low Density Lipoprotein Subfraction, Adiponectin and Apolipoprotein B in Type 2 Diabetic Patients

Abstract

Background

Omega-3 fatty acids derived from fish oil have been reported to exert a beneficial effect on reducing cardiovascular disease. Reports about their mechanism have generated several interesting findings, including a change in small dense low density lipoprotein (sdLDL) cholesterol proportion, adiponectin, and apolipoprotein B (apoB), in addition to changes in the lipid profile. The principal objective of our study was to evaluate the effects of omega-3 fatty acids on plasma sdLDL, adiponectin, apoB100, and B48 in type 2 diabetic patients with hypertriglyceridemia.

Methods

We randomized 28 type 2 diabetic patients in a placebo-controlled, double-blind trial to receive either omega-3 fatty acids or placebo, both administered at a dose of 4 g daily for 12 weeks. LDL subfractions prior to and after treatment were separated via low-speed ultracentrifugation and analyzed via immunoelectrophoresis. Adiponectin, apoB100, and B48 levels were measured using an ELISA kit.

Results

sdLDL proportions were reduced in the omega-3 fatty acids group by 11% after 12 weeks of treatment (n = 17, P = 0.001), and were reduced by 4% in the control group (n = 11, P = 0.096). The patients receiving the omega-3 fatty acids evidenced a significant reduction in the levels of triglyceride (P = 0.001), apoB100, and B48 after 12 weeks (P = 0.038 and P = 0.009, respectively) relative to the baseline. Omega-3 fatty acids supplementation increased fasting blood glucose (P = 0.011), but the levels of HbA1c in each group did not change to a statistically significance degree. The adiponectin value was not reduced in the omega-3 fatty acids group (P = 0.133); by way of contrast, the placebo group evidenced a significant reduction in adiponectin value after 12 weeks (P = 0.002).

Conclusion

Omega-3 fatty acid treatment proved effective in the reduction of atherogenic sdLDL and apoB in type 2 diabetic patients (Clinical trials reg. no. NCT 00758927, clinicaltrials.gov).

Figures and Tables

Fig. 1
Sucrose and 3-10% poly-acrylamide gel gradient. A. 5-10% Sucrose gradient. LDL density is 1.02-1.044 g/mL and sdLDL density is 1.044-1.060. B. Poly-acrylamide gradient gels are casted using a 2-chamber gradient mixer. Preelectrophoresis for 60 min at 50 V and electrophoresis are performed by using running buffer (90 mM Tris, 80 mM boric acid, and 2.5 mM pH 8.35 Na2-EDTA) with cooling from a (Multitemp II, Pharmacia-LKB) set at 10℃. A total volume of 25 µL of sample, containing 3 µg of LDL protein, is applied to each well and electrophoresis is conducted at 20 V for 15 minute, then to 70 V for 15 minute, and finally to 125 V for 24 hours. After electrophoresis, gel is stained with Oil Red O and then Coomassie Brilliant Blue G-250.
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Fig. 2
The effects of sdLDL (A), adiponectin (B), apoB100 (C) and apoB48 (D) in type 2 diabetic patients with omega-3 fatty acids. sdLDL, apoB100 and B48 were significantly decreased after 12 weeks treatment with omega-3 fatty acids. Adiponectin values were not changed.
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Table 1
Baseline characteristics of subjects
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The 2 groups did not differ significantly with regard to any of these variables in student t-tests. All values were expressed as mean ± standard deviation.

Table 2
Changes of metabolic parameters from baseline to week 12 in the omega?? fatty acids and placebo group
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HDL, high density lipoprotein cholesterol; LDL, low density lipoprotein cholesterol. *Statistical significance test was done by paired t-test vs. baseline (P < 0.05).

References

1. Xiao YF, Sigg DC, Leaf A. The antiarrhythmic effect of n-3 polyunsaturated fatty acids: modulation of cardiac ion channels as a potential mechanism. J Membr Biol. 2005. 206:141–154.
2. Engelbrecht AM, Engelbrecht P, Genade S, Niesler C, Page C, Smuts M, Lochner A. Long-chain polyunsaturated fatty acids protect the heart against ischemia/reperfusion-induced injury via a MAPK dependent pathway. J Mol Cell Cardiol. 2005. 39:940–954.
3. Harrison N, Abhyankar B. The mechanism of action of omega-3 fatty acids in secondary prevention post-myocardial infarction. Curr Med Res Opin. 2005. 21:95–100.
4. Geelen A, Brouwer IA, Zock PL, Katan MB. Antiarrhythmic effects of n-3 fatty acids: evidence from human studies. Curr Opin Lipidol. 2004. 15:25–30.
5. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002. 106:2747–2757.
6. Connor WE. Importance of n-3 fatty acids in health and disease. Am J Clin Nutr. 2000. 71:171S–175S.
7. Gadi R, Samaha FF. Dyslipidemia in type 2 diabetes mellitus. Curr Diab Rep. 2007. 7:228–234.
8. Friedberg CE, Janssen MJ, Heine RJ, Grobbee DE. Fish oil and glycemic control in diabetes. A meta-analysis. Diabetes Care. 1998. 21:494–500.
9. Montori VM, Farmer A, Wollan PC, Dinneen SF. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care. 2000. 23:1407–1415.
10. Walldius G, Jungner I. The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy--a review of the evidence. J Intern Med. 2006. 259:493–519.
11. Valdivielso P, Rioja J, García-Arias C, Sánchez-Chaparro MA, González-Santos P. Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report. Cardiovasc Diabetol. 2009. 8:1.
12. Yamauchi T, Hara K, Kubota N, Terauchi Y, Tobe K, Froguel P, Nagai R, Kadowaki T. Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. Curr Drug Targets Immune Endocr Metabol Disord. 2003. 3:243–254.
13. Krakoff J, Funahashi T, Stehouwer CD, Schalkwijk CG, Tanaka S, Matsuzawa Y, Kobes S, Tataranni PA, Hanson RL, Knowler WC, Lindsay RS. Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diabetes Care. 2003. 26:1745–1751.
14. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001. 86:1930–1935.
15. Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, Retzlaff BM, Knopp RH, Brunzell JD, Kahn SE. 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.
16. Menzaghi C, Trischitta V, Doria A. Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes. 2007. 56:1198–1209.
17. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001. 37:1236–1241.
18. Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, Shulman GI. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes. 2006. 55:924–928.
19. Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M, Ruzickova J, Kopecky J. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia. 2006. 49:394–397.
20. Guebre-Egziabher F, Rabasa-Lhoret R, Bonnet F, Bastard JP, Desage M, Skilton MR, Vidal H, Laville M. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. Eur J Clin Nutr. 2008. 62:1287–1293.
21. Lara JJ, Economou M, Wallace AM, Rumley A, Lowe G, Slater C, Caslake M, Sattar N, Lean ME. Benefits of salmon eating on traditional and novel vascular risk factors in young, non-obese healthy subjects. Atherosclerosis. 2007. 193:213–221.
22. Kratz M, Swarbrick MM, Callahan HS, Matthys CC, Havel PJ, Weigle DS. Effect of dietary n-3 polyunsaturated fatty acids on plasma total and high-molecular-weight adiponectin concentrations in overweight to moderately obese men and women. Am J Clin Nutr. 2008. 87:347–353.
23. Borkman M, Chisholm DJ, Furler SM, Storlien LH, Kraegen EW, Simons LA, Chesterman CN. Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM. Diabetes. 1989. 38:1314–1319.
24. Malasanos TH, Stacpoole PW. Biological effects of omega-3 fatty acids in diabetes mellitus. Diabetes Care. 1991. 14:1160–1179.
25. Koba S, Hirano T, Yoshino G, Sakai K, Sakaue T, Adachi M, Katagiri T. Remarkably high prevalence of small dense low-density lipoprotein in Japanese men with coronary artery disease, irrespective of the presence of diabetes. Atherosclerosis. 2002. 160:249–256.
26. Nettleton JA, Katz R. n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc. 2005. 105:428–440.
27. St-Pierre AC, Cantin B, Dagenais GR, Mauriege P, Bernard PM, Despres JP, Lamarche B. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol. 2005. 25:553–559.
28. St-Pierre AC, Cantin B, Dagenais GR, Despres JP, Lamarche B. Apolipoprotein-B, low-density lipoprotein cholesterol, and the long-term risk of coronary heart disease in men. Am J Cardiol. 2006. 97:997–1001.
29. Kim E, Young SG. Genetically modified mice for the study of apolipoprotein B. J Lipid Res. 1998. 39:703–723.
30. Hogue JC, Lamarche B, Tremblay AJ, Bergeron J, Gagne C, Couture P. Evidence of increased secretion of apolipoprotein B-48-containing lipoproteins in subjects with type 2 diabetes. J Lipid Res. 2007. 48:1336–1342.
31. 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.
32. Kondo K, Morino K, Nishio Y, Kondo M, Fuke T, Ugi S, Iwakawa H, Kashiwagi A, Maegawa H. Effects of a fish-based diet on the serum adiponectin concentration in young, non-obese, healthy Japanese subjects. J Atheroscler Thromb. 2010. 17:628–637.
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