Hostname: page-component-7c8c6479df-94d59 Total loading time: 0 Render date: 2024-03-27T16:50:31.528Z Has data issue: false hasContentIssue false

n-3 Polyunsaturated fatty acids, inflammation and obesity-related disease

Published online by Cambridge University Press:  05 March 2007

Lucy M. Browning*
Affiliation:
MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL, UK
*
Corresponding author: Lucy M. Browning, fax +44 1223 437515, Lucy.Browning@mrc-hnr.cam.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Obese individuals are at increased risk from a range of metabolic diseases, including insulin resistance, dyslipidaemia and hypertension. Adipose tissue is an important endocrine organ, secreting a range of inflammatory mediators, including tumour necrosis factor a and interleukin 6. Circulating concentrations of these cytokines are increased in obesity and may contribute to the pathogenesis of metabolic diseases. The present review considers the evidence linking inflammation and obesity-related disease. The data show that an inflammatory phenotype, measured by serum sialic acid concentration, identifies individuals with insulin resistance, dyslipidaemia and hypertension. Serum sialic acid concentration increases progressively in obese individuals with none, one or multiple features of the metabolic syndrome, independent of BMI. Supplementation with long-chain n-3 polyunsaturated fatty acids has shown anti-inflammatory effects in studies of both healthy populations and in models of chronic inflammatory conditions. The effect on insulin sensitivity has been varied, with both positive and negative effects. This variability may relate to the metabolic characteristics of the study population; individuals with high background inflammation may derive greater benefits from n-3 polyunsaturated fatty acid supplements, suggesting a possible interaction between diet and phenotype. Future research is needed to fully evaluate the role of anti-inflammatory strategies in the dietary management of obesity.

Type
Micronutrient Group Symposium on ‘Micronutrient supplementation: when and why?’
Copyright
Copyright © The Nutrition Society 2003

References

Alexander, JK (2001) Obesity and coronary heart disease. American Journal of Medical Sciences 321, 215224CrossRefGoogle ScholarPubMed
Andrews, RC & Walker, BR (1999) Glucocorticoids and insulin resistance: old hormones, new targets. Clinical Science 96, 513523CrossRefGoogle ScholarPubMed
Belluzzi, A, Brignola, C, Campieri, M, Pera, A, Boschi, S & Miglioli, M (1996) Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. New England Journal of Medicine 334, 15571560CrossRefGoogle ScholarPubMed
Bjerregaard, P, Pedersen, HS & Mulvad, G (2000) The associations of a marine diet with plasma lipids, blood glucose, blood pressure and obesity among the Inuit in Greenland. European Journal of Clinical Nutrition 54, 732737CrossRefGoogle ScholarPubMed
Bjorntorp, P & Rosmond, R (2000) The metabolic syndrome–a neuroendocrine disorder?. British Journal of Nutrition 83, S49S57CrossRefGoogle ScholarPubMed
Broughton, KS, Johnson, CS, Pace, BK, Liebman, M & Kleppinger, KM (1997) Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotriene production. American Journal of Clinical Nutrition 65, 10111017CrossRefGoogle ScholarPubMed
Browning, LM, Krebs, JK, O'Connell, MA, Mishra, GD & Jebb, SA (2002) n -3 PUFA supplementation improves insulin sensitivity in a group of overweight women with an inflammatory phenotype. Proceedings of the Nutrition Society 61 123AGoogle Scholar
Browning, LM, O'Connell, MA & Jebb, SA (2001) Inter- and intraindividual variability in acute phase response markers among overweight adults. Annals of Nutrition and Metabolism 45, 290 Suppl. 1Google Scholar
Bucher, HC, Hengstler, P, Schindler, C & Meier, G (2002) n-3 Polyunsaturated fatty acids in coronary heart disease: a metaanalysis of randomized controlled trials. American Journal of Medicine 112, 298304CrossRefGoogle Scholar
Calle, EE, Thun, MJ, Petrelli, JM, Rodriguez, C & Heath CW, Jr (1999) Body-mass index and mortality in a prospective cohort of U.S. adults. New England Journal of Medicine 341, 10971105CrossRefGoogle Scholar
Caughey, GE, Mantzioris, E, Gibson, RA, Cleland, LG & James, MJ (1996) The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n -3 fatty acids from vegetable oil or fish oil. American Journal of Clinical Nutrition 63, 116122CrossRefGoogle ScholarPubMed
Chae, CU, Lee, RT, Rifai, N & Ridker, PM (2001) Blood pressure and inflammation in apparently healthy men. Hypertension 38, 399403CrossRefGoogle ScholarPubMed
Chan, JM, Rimm, EB, Colditz, GA, Stampfer, MJ & Willett, WC (1994) Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 17, 961969CrossRefGoogle ScholarPubMed
Colditz, GA, Willett, WC, Stampfer, MJ, Manson, JE, Hennekens, CH, Arky, RA & Speizer, FE (1990) Weight as a risk factor for clinical diabetes in women. American Journal of Epidemiology 132, 501513CrossRefGoogle ScholarPubMed
Crook, M, Lumb, P, Andrews, V & Swaminathan, R (1998) Serum total sialic acid, a reputed cardiovascular risk factor, and its relationship to lipids, plasma fasting insulin, blood pressure and body mass index in normal individuals. Clinical Science 95, 5357CrossRefGoogle ScholarPubMed
Dalziel, B, Gosby, AK, Richman, RM, Bryson, JM & Caterson, ID (2002) Association of the TNF-alpha-308 G/A promoter polymorphism with insulin resistance in obesity. Obesity Research 10, 401407CrossRefGoogle ScholarPubMed
Dandona, P, Weinstock, R, Thusu, K, Abdel-Rahman, E, Aljada, A & Wadden, T (1998) Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. Journal of Clinical Endocrinology and Metabolism 83, 29072910Google ScholarPubMed
Danesh, J (1999) Smoldering arteries? Low-grade inflammation and coronary heart disease. Journal of the American Medical Association 282, 21692171CrossRefGoogle ScholarPubMed
Department of Health (1994) Nutritional Aspects of Cardiovascular Disease. Report on Health and Social Subjects no. 46 London: H. M. Stationery Office.Google Scholar
Dyerberg, J & Bang, HO (1979) Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet ii, 433435CrossRefGoogle Scholar
Endres, S, Ghorbani, R, Kelley, VE, Georgilis, K, Lonnemann, G, van, der, Meer, JW, Cannon, JG, Rogers, TS, Klempner, MS & Weber, PC (1989) The effect of dietary supplementation with n -3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. New England Journal of Medicine 320, 265271CrossRefGoogle Scholar
Eritsland, J, Seljeflot, I, Abdelnoor, M, Arnesen, H & Torjesen, PA (1994) Long-term effects of n -3 fatty acids on serum lipids and glycaemic control. Scandinavian Journal of Clinical and Laboratory Investigation 54, 273280CrossRefGoogle Scholar
Festa, A, D'Agostino, R, Jr, Tracy, RP Haffner, SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51, 11311137CrossRefGoogle ScholarPubMed
Frayn, KN (2001) Adipose tissue and the insulin resistance syndrome. Proceedings of the Nutrition Society 60, 375380CrossRefGoogle ScholarPubMed
Fruhbeck, G, Gomez-Ambrosi, J, Muruzabal, FJ & Burrell, MA (2001) The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. American Journal of Physiology 280, E827E847Google Scholar
Geusens, P, Wouters, C, Nijs, J, Jiang, Y & Dequeker, J (1994) Longterm effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12 month, double blind, controlled study. Arthritis and Rheumatism 37, 824829CrossRefGoogle ScholarPubMed
Grimble, RF (1998) Dietary lipids and the inflammatory response. Proceedings of the Nutrition Society 57, 535542CrossRefGoogle ScholarPubMed
Hughes, DA (1998) In vitro and in vivo effects of n -3 polyunsaturated fatty acids on human monocyte function. Proceedings of the Nutrition Society 57, 521525CrossRefGoogle Scholar
Humphries, SE, Luong, LA, Ogg, MS, Hawe, E & Miller, GJ (2001) The interleukin-6–174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. European Heart Journal 22, 22432252CrossRefGoogle ScholarPubMed
Kern, PA, Ranganathan, S, Li, C, Wood, L & Ranganathan, G (2001) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. American Journal of Physiology 280, E745E751Google ScholarPubMed
Kern, PA, Saghizadeh, M, Ong, JM, Bosch, RJ, Deem, R & Simsolo, RB (1995) The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. Journal of Clinical Investigation 95, 21112119CrossRefGoogle ScholarPubMed
Krebs, JD, Browning, LM, Cooke, JH, O'Connell, MA, Mishra, GD & Jebb, SA (2002) Elevated sialic acid predicts features of the metabolic syndrome. Diabetologia 45 A16Google Scholar
Landsberg, L (1999) Role of the sympathetic adrenal system in the pathogenesis of the insulin resistance syndrome. Annals of the New York Academy of Sciences 892, 8490CrossRefGoogle ScholarPubMed
Lee, TH, Hoover, R, Williams, JD, Sperling, J, Raralese, J, Spur, BW, Robinson, DR, Corey, EJ, Lewis, RA & Austen, KF (1985) Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acid on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. New England Journal of Medicine 312, 12171224CrossRefGoogle ScholarPubMed
Liu, S, Manson, JE, Buring, JE, Stampfer, MJ, Willett, WC & Ridker, PM (2002) Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. American Journal of Clinical Nutrition 75, 492498CrossRefGoogle ScholarPubMed
Liu, S, Willett, WC, Stampfer, MJ, Hu, FB, Franz, M, Sampson, L, Hennekens, CH & Manson, JE (2000) A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. American Journal of Clinical Nutrition 71, 14551461CrossRefGoogle ScholarPubMed
McManus, RM, Jumpson, J, Finegood, DT, Clandinin, MT & Ryan, EA (1996) A comparison of the effects of n -3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. Diabetes Care 19, 463467CrossRefGoogle Scholar
Manson, JE, Colditz, GA, Stampfer, MJ, Willett, WC, Rosner, B, Monson, RR, Speizer, FE & Hennekens, CH (1990) A prospective study of obesity and risk of coronary heart disease in women. New England Journal of Medicine 322, 882889CrossRefGoogle ScholarPubMed
Mayser, P, Mrowietz, U, Arenberger, P, Bartak, P, Buchvald, J, Christophers, E, Jablonska, S, Salmhofer, W, Schill, WB, Kramer, HJ, Schlotzer, E, Mayer, K, Seeger, W & Grimminger, F (1998) Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial. Journal of the American Academy of Dermatology 38, 539547CrossRefGoogle ScholarPubMed
Mori, TA, Bao, DQ, Burke, V, Puddey, IB, Watts, GF & Beilin, LJ (1999) Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects. American Journal of Clinical Nutrition 70, 817825CrossRefGoogle Scholar
Mulrooney, HM & Grimble, RF (1993) The influence of butter, and corn, coconut and fish oils on the effects of recombinant human tumour necrosis factor alpha in rats. Clinical Science 84, 105112CrossRefGoogle ScholarPubMed
Ofei, F, Hurel, S, Newkirk, J, Sopwith, M & Taylor, R (1996) Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45, 881885CrossRefGoogle ScholarPubMed
Popp-Snijders, C, Schouten, JA, Heine, RJ, van, der, Meer, J, van, der & Veen, EA (1987) Dietary supplementation of omega-3 polyunsaturated fatty acids improves insulin sensitivity in non-insulin-dependent diabetes. Diabetes Research 4, 141147Google ScholarPubMed
Pradhan, AD, Manson, JE, Rifai, N, Buring, JE & Ridker, PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Journal of the American Medical Association 286, 327334CrossRefGoogle ScholarPubMed
Ridker, PM (2001) High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 103, 18131818CrossRefGoogle ScholarPubMed
Ridker, PM, Hennekens, CH, Burling, JE & Rifai, N (2000) C-Reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New England Journal of Medicine 342, 836843CrossRefGoogle Scholar
Ridker, PM, Stampfer, MJ & Rifai, N (2001) Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. Journal of the American Medical Association 285, 24812485CrossRefGoogle ScholarPubMed
Sadeghi, S, Wallace, FA & Calder, PC (1999) Dietary lipids modify the cytokine response to bacterial lipopolysaccharide in mice. Immunology 96, 404410CrossRefGoogle ScholarPubMed
Saynor, R & Gillott, T (1992) Changes in blood lipids and fibrinogen with a note on safety in a long-term study of the effects of n -3 fatty acids in subjects receiving fish oil supplements and followed for seven years. Lipids 27, 533538CrossRefGoogle Scholar
Schmidt, MI, Duncan, BB, Sharrett, AR, Lindberg, G, Savage, PJ, Offenbacher, S, Azambuja, MI, Tracy, RP & Heiss, G (1999) Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities Study): a cohort study. Lancet 353, 16491652CrossRefGoogle Scholar
Simopoulos, AP (1999) Essential fatty acids in health and chronic disease. American Journal of Clinical Nutrition 70, 560S569SCrossRefGoogle ScholarPubMed
Sperling, RI (1998) The effects of dietary n -3 polyunsaturated fatty acids on neutrophils. Proceedings of the Nutrition Society 57, 527534CrossRefGoogle ScholarPubMed
Storlien, LH, Kraegen, EW, Chisholm, DJ, Ford, GL, Bruce, DG & Pascoe, WS (1987) Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 237, 885888CrossRefGoogle ScholarPubMed
Tsigos, C, Kyrou, I, Chala, E, Tsapogas, P, Stavridis, JC, Raptis, SA & Katsilambros, N (1999) Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity. Metabolism 48, 13321335CrossRefGoogle ScholarPubMed
Uysal, KT, Wiesbrock, SM, Marino, MW & Hotamisligil, GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389, 610614CrossRefGoogle ScholarPubMed
Vessby, B & Boberg, M (1990) Dietary supplementation with n -3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. Journal of Internal Medicine 228, 165171CrossRefGoogle Scholar
Vessby, B, Unsitupa, M, Hermansen, K, Riccardi, G, Rivellese, AA, Tapsell, LC, Nalsen, C, Berglund, L, Louheranta, A, Rasmussen, BM, Calvert, GD, Maffetone, A, Pedersen, E, Gustafsson, IB & Storlien, LH (2001) Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia 44, 312319CrossRefGoogle ScholarPubMed
Vickers, MA, Green, FR, Terry, C, Mayosi, BM, Julier, C, Lathrop, M, Ratcliffe, PJ, Watkins, HC & Keavney, B (2002) Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovascular Research 53, 10291034CrossRefGoogle Scholar
Vognild, E, Elvevoll, EO, Brox, J, Olsen, RL, Barstad, H, Aursand, M & Osterud, B (1998) Effects of dietary marine oils and olive oil on fatty acid composition, platelet membrane fluidity, platelet responses, and serum lipids in healthy humans. Lipids 33, 427436CrossRefGoogle ScholarPubMed
Yaqoob, P, Knapper, JA, Webb, DH, Williams, CM, Newsholme, EA & Calder, PC (1998) Effect of olive oil on immune function in middle-aged men. American Journal of Clinical Nutrition 67, 129135CrossRefGoogle ScholarPubMed
Yudkin, JS, Stehouwer, CDA, Emeis, JJ & Coppack, SW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction. Arteriosclerosis, Thrombosis and Vascular Biology 19, 972978CrossRefGoogle ScholarPubMed