RSS-Feed abonnieren
DOI: 10.1055/s-0028-1085459
© Georg Thieme Verlag KG Stuttgart · New York
Selective Association of Plasma Non-esterified Fatty Acid Species with Circulating Interleukin-8 Concentrations in Humans
Publikationsverlauf
received 23.08.2007
first decision 07.01.2008
accepted 23.01.2008
Publikationsdatum:
03. Dezember 2008 (online)
![](https://www.thieme-connect.de/media/eced/200901/lookinside/thumbnails/10.1055-s-0028-1085459-1.jpg)
Abstract
Elevated plasma concentrations of non-esterified fatty acids (NEFA), due to high fat intake and/or adipose tissue lipolysis, are a hallmark of the metabolic syndrome. We assessed whether certain plasma NEFA species contribute to the chronic low-grade inflammatory state seen in the metabolic syndrome. We determined the fasting plasma NEFA patterns of 75 overweight non-diabetic subjects and analysed their relationship with plasma inflammatory parameters. After adjustment for gender, age, body fat, and waist-hip ratio, no strong correlations of single NEFA species with leukocyte number, C-reactive protein, interleukin-6, tumour necrosis factor-α, or monocyte chemoattractant protein-1 were detected. However, oleate was negatively (r=−0.36, p=0.0015) and myristate (r=0.41, p=0.0003) as well as the ω3-polyunsaturated NEFA α-linolenate (r=0.37, p=0.0011), eicosapentaenoate (r=0.40, p=0.0003), and docosahexaenoate (r=0.40, p=0.0004) were positively associated with interleukin-8 concentrations. The other NEFA species as well as the total plasma NEFA concentration did not correlate with interleukin-8. The correlations of myristate, oleate, and the sum of all ω3-polyunsaturated NEFA with interleukin-8 were independent of plasma tumour necrosis factor-α and overall adiposity. Our data demonstrate close and selective associations of oleate, myristate, and ω3-polyunsaturated NEFA with plasma concentrations of the pro-inflammatory chemokine interleukin-8. Thus, these NEFA species may represent specific determinants of plasma interleukin-8.
Key words
fatty acids - ω3-PUFA - inflammation - cytokines - interleukin-8 - metabolic syndrome
References
- 1 Ajuwon KM, Spurlock ME. Palmitate activates the NF-kappaB transcription factor and induces IL-6 and TNFalpha expression in 3T3-L1 adipocytes. J Nutr. 2005; 135 1841-1846
- 2 Arner P. Insulin resistance in type 2 diabetes: role of fatty acids. Diabetes Metab Res Rev. 2002; 18 ((Suppl 2)) S5-S9
- 3 Bang HO, Dyerberg J. Plasma lipids and lipoproteins in Greenlandic west coast Eskimos. Acta Med Scand. 1972; 192 85-94
- 4 Barzilay J, Freedland E. Inflammation and its association with glucose disorders and cardiovascular disease. Treat Endocrinol. 2003; 2 85-94
- 5 Bhatnagar D, Durrington PN. Omega-3 fatty acids: their role in the prevention and treatment of atherosclerosis related risk factors and complications. Int J Clin Pract. 2003; 57 305-314
- 6 Bruun JM, Pedersen SB, Richelsen B. Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro. J Clin Endocrinol Metab. 2001; 86 1267-1273
- 7 Bucher HC, Hengstler P, Schindler C. et al . N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002; 112 298-304
- 8 Calder PC, Harvey DJ, Pond CM. et al . Site-specific differences in the fatty acid composition of human adipose tissue. Lipids. 1992; 27 716-720
- 9 Caterina R De, Massaro M. Omega-3 fatty acids and the regulation of expression of endothelial pro-atherogenic and pro-inflammatory genes. J Membr Biol. 2005; 206 103-116
- 10 Lorgeril M de, Salen P, Martin JL. et al . Effect of a mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease. Insights into the cardioprotective effect of certain nutriments. J Am Coll Cardiol. 1996; 28 1103-1108
- 11 Dimopoulos N, Watson M, Sakamoto K. et al . Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells. Biochem J. 2006; 399 473-481
- 12 Din JN, Newby DE, Flapan AD. Omega 3 fatty acids and cardiovascular disease – fishing for a natural treatment. BMJ. 2004; 328 30-35
- 13 Eitel K, Staiger H, Brendel MD. et al . Different role of saturated and unsaturated fatty acids in beta-cell apoptosis. Biochem Biophys Res Commun. 2002; 299 853-856
- 14 Eitel K, Staiger H, Rieger J. et al . Protein kinase C delta activation and translocation to the nucleus are required for fatty acid-induced apoptosis of insulin-secreting cells. Diabetes. 2003; 52 991-997
- 15 Erkkila AT, Lichtenstein AH, Mozaffarian D. et al . Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Am J Clin Nutr. 2004; 80 626-632
- 16 Fernandez-Real JM, Broch M, Vendrell J. et al . Insulin resistance, inflammation, and serum fatty acid composition. Diabetes Care. 2003; 26 1362-1368
- 17 Festa A, D’Agostino Jr R, Howard G. et al . Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2000; 102 42-47
- 18 Geelen A, Brouwer IA, Zock PL. et al . Antiarrhythmic effects of n-3 fatty acids: evidence from human studies. Curr Opin Lipidol. 2004; 15 25-30
- 19 Haban P, Klvanova J, Zidekova E. et al . Dietary supplementation with olive oil leads to improved lipoprotein spectrum and lower n-6 PUFAs in elderly subjects. Med Sci Monit. 2004; 10 I49-I54
- 20 Hak AE, Pols HA, Stehouwer CD. et al . Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study. J Clin Endocrinol Metab. 2001; 86 4398-4405
- 21 Hartweg J, Farmer AJ, Holman RR. et al . Meta-analysis of the effects of n-3 polyunsaturated fatty acids on haematological and thrombogenic factors in type 2 diabetes. Diabetologia. 2007; 50 250-258
- 22 Herder C, Baumert J, Thorand B. et al . Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984-2002. Diabetologia. 2006a; 49 921-929
- 23 Herder C, Baumert J, Thorand B. et al . Chemokines and incident coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Arterioscler Thromb Vasc Biol. 2006b; 26 2147-2152
- 24 Herder C, Haastert B, Muller-Scholze S. et al . Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Diabetes. 2005; 54 ((Suppl 2)) S11-S17
- 25 Hoffmann E, Dittrich-Breiholz O, Holtmann H. et al . Multiple control of interleukin-8 gene expression. J Leukoc Biol. 2002; 72 847-855
- 26 Hooper L, Thompson RL, Harrison RA. et al . Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006; 332 752-760
- 27 Houdali B, Wahl HG, Kresi M. et al . Glucose oversupply increases delta9-desaturase expression and its metabolites in rat skeletal muscle. Diabetologia. 2003; 46 203-212
- 28 Hu FB, Cho E, Rexrode KM. et al . Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation. 2003; 107 1852-1857
- 29 Hughes-Fulford M, Li CF. et al . Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces gene expression in prostate cancer. Cancer Res. 2006; 66 1427-1433
- 30 Kausch C, Staiger H, Staiger K. et al . Skeletal muscle cells from insulin-resistant (non-diabetic) individuals are susceptible to insulin desensitization by palmitate. Horm Metab Res. 2003; 35 570-576
- 31 Kim CS, Park HS, Kawada T. et al . Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond). 2006; 30 1347-1355
- 32 Klein-Platat C, Drai J, Oujaa M. et al . Plasma fatty acid composition is associated with the metabolic syndrome and low-grade inflammation in overweight adolescents. Am J Clin Nutr. 2005; 82 1178-1184
- 33 Leinonen E, Hurt-Camejo E, Wiklund O. et al . Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes. Atherosclerosis. 2003; 166 387-394
- 34 Mohamed-Ali V, Goodrick S, Rawesh A. et al . Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab. 1997; 82 4196-4200
- 35 Nettleton JA. Omega-3 fatty acids: comparison of plant and seafood sources in human nutrition. J Am Diet Assoc. 1991; 91 331-337
- 36 Renaud S, Lorgeril M de, Delaye J. et al . Cretan Mediterranean diet for prevention of coronary heart disease. Am J Clin Nutr. 1995; 61 1360S-1367S
- 37 Ruiz-Gutierrez V, Montero E, Villar J. Determination of fatty acid and triacylglycerol composition of human adipose tissue. J Chromatogr. 1992; 581 171-178
- 38 Ryan M, MacInerney D, Owens D. et al . Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependent vasoreactivity. QJM. 2000; 93 85-91
- 39 Staiger H, Staiger K, Stefan N. et al . Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells. Diabetes. 2004; 53 3209-3216
- 40 Stefan N, Wahl HG, Fritsche A. et al . Effect of the pattern of elevated free fatty acids on insulin sensitivity and insulin secretion in healthy humans. Horm Metab Res. 2001; 33 432-438
- 41 Straczkowski M, Dzienis-Straczkowska S, Stepien A. et al . Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. J Clin Endocrinol Metab. 2002; 87 4602-4606
- 42 Temelkova-Kurktschiev T, Henkel E, Koehler C. et al . Subclinical inflammation in newly detected type II diabetes and impaired glucose tolerance. Diabetologia. 2002; 45 151
- 43 Thies F, Garry JM, Yaqoob P. et al . Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet. 2003; 361 477-485
- 44 Toborek M, Lee YW, Garrido R. et al . Unsaturated fatty acids selectively induce an inflammatory environment in human endothelial cells. Am J Clin Nutr. 2002; 75 119-125
- 45 Weigert C, Brodbeck K, Staiger H. et al . Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factor-kappaB. J Biol Chem. 2004; 279 23942-23952
- 46 Woo LY, Joo PH, Hennig B. et al . Linoleic acid induces MCP-1 gene expression in human microvascular endothelial cells through an oxidative mechanism. J Nutr Biochem. 2001; 12 648-654
Correspondence
Prof. Dr. med. H.-U. Häring
Internal Medicine IV
Medical Clinic Tübingen
Otfried-Müller-Str. 10
72076 Tübingen
Germany
Telefon: +49/7071/298 27 35
Fax: +49/7071/29 27 84
eMail: hans-ulrich.haering@med.uni-tuebingen.de