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  • Original Article
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Nutritional intervention to reduce the n−6/n−3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects

Abstract

Background/Objectives:

Consumption of n−3 polyunsaturated fatty acids (PUFA) has a favourable impact on inflammation and cardiovascular disease. However, the Western diet is characterized by a low n−3 PUFA intake and an imbalance in the n−6/n−3 PUFA ratio. Study the effect 10-week of diet modification to decrease the n−6/n−3 PUFA ratio on cardiovascular risk factors and resting energy expenditure.

Subjects and methods:

Ten-week dietary intervention in 17 healthy subjects. Dietary intake, euglycemic hyperinsulinemic clamp, indirect calorimetry, lipid profile, hormones, inflammatory markers and erythrocyte membrane fatty acid composition were recorded before and at the end of the intervention. Comparisons are between baseline and post-treatment levels.

Results:

Dietary records of the linoleic acid/α-linolenic acid ratio (baseline: 32.2 (s.d. 3.7) vs post-intervention: 2.2 (s.d. 0.1), P<0.0001) and erythrocyte membrane fatty acid composition reflected good compliance. Dietary intervention was associated with significant reductions in TNF-α (baseline: 2.2 (s.d. 0.3), post-intervention: 1.5 (s.d. 0.3) pg/ml, P=0.01) and low-density lipoprotein-cholesterol (baseline: 2.5 (s.d. 0.2), post-intervention: 2.3 (s.d. 0.1) mmol/l, P=0.03) and increased adiponectin (baseline: 6.5 (s.d. 0.7), post-intervention: 7.6 (s.d. 0.6) μg/ml, P=0.02). Fasting lipid oxidation was increased (baseline: 0.7 (s.d. 0.1), post-intervention: 0.9 (s.d. 0.1) mg/kg.min, P=0.01), whereas glucose oxidation decreased in both fasting (baseline: 1.6 (s.d. 0.1), post-intervention: 1.3 (s.d. 0.1) mg/kg.min, P=0.02) and hyperinsulinaemic conditions (baseline: 3.6 (s.d. 0.1), post-intervention: 3.3 (s.d. 0.1) mg/kg.min, P=0.04). Insulin sensitivity was not affected by the intervention.

Conclusion:

A decreased n−6/n−3 PUFA ratio can be achieved with simple dietary counselling, resulting in multiple, potentially favourable effects on the metabolic and inflammatory profiles.

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References

  • Albert CM, Campos H, Stampfer MJ, Ridker PM, Manson JE, Willett WC et al. (2002). Blood levels of long-chain n−3 fatty acids and the risk of sudden death. N Engl J Med 346, 1113–1118.

    Article  CAS  Google Scholar 

  • Baker PW, Gibbons GF (2000). Effect of dietary fish oil on the sensitivity of hepatic lipid metabolism to regulation by insulin. J Lipid Res 41, 719–726.

    CAS  PubMed  Google Scholar 

  • Bligh EG, Dyer WJ (1959). A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37, 911–917.

    Article  CAS  Google 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. Am J Clin Nutr 63, 116–122.

    Article  CAS  Google Scholar 

  • Clarke SD (2001). Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome. J Nutr 131, 1129–1132.

    Article  CAS  Google Scholar 

  • Connor WE (2000). Importance of n−3 fatty acids in health and disease. Am J Clin Nutr 71, 171S–175S.

    Article  CAS  Google Scholar 

  • Couet C, Delarue J, Ritz P, Antoine JM, Lamisse F (1997). Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes Relat Metab Disord 21, 637–643.

    Article  CAS  Google Scholar 

  • de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N (1999). Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 99, 779–785.

    Article  CAS  Google Scholar 

  • Deharveng G, Charrondiere UR, Slimani N, Southgate DA, Riboli E (1999). Comparison of nutrients in the food composition tables available in the nine European countries participating in EPIC. European prospective investigation into cancer and nutrition. Eur J Clin Nutr 53, 60–79.

    Article  CAS  Google Scholar 

  • Delarue J, LeFoll C, Corporeau C, Lucas D (2004). n−3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? Reprod Nutr Dev 44, 289–299.

    Article  CAS  Google Scholar 

  • Ducluzeau PH, Perretti N, Laville M, Andreelli F, Vega N, Riou JP et al. (2001). Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes. Diabetes 50, 1134–1142.

    Article  CAS  Google Scholar 

  • Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW et al. (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. N Engl J Med 320, 265–271.

    Article  CAS  Google Scholar 

  • Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J et al. (2003). Association between adiponectin and mediators of inflammation in obese women. Diabetes 52, 942–947.

    Article  CAS  Google Scholar 

  • Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M et al. (2006). Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia 49, 394–397.

    Article  CAS  Google Scholar 

  • Friberg P, Johansson M (2007). Effects of an omega-3-enriched Mediterranean diet (modified diet of Crete) versus a Swedish diet. World Rev Nutr Diet 97, 52–66.

    CAS  PubMed  Google Scholar 

  • Gerster H (1998). Can adults adequately convert alpha-linolenic acid (18:3n−3) to eicosapentaenoic acid (20:5n−3) and docosahexaenoic acid (22:6n−3)? Int J Vitam Nutr Res 68, 159–173.

    CAS  PubMed  Google Scholar 

  • GISSI-Prevenzione-Investigators (1999). Dietary supplementation with n−3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 354, 447–455.

    Article  Google Scholar 

  • Halvorsen B, Rustan AC, Madsen L, Reseland J, Berge RK, Sletnes P et al. (2001). Effects of long-chain monounsaturated and n−3 fatty acids on fatty acid oxidation and lipid composition in rats. Ann Nutr Metab 45, 30–37.

    Article  CAS  Google Scholar 

  • He K, Daviglus ML (2005). A few more thoughts about fish and fish oil. J Am Diet Assoc 105, 350–351.

    Article  Google Scholar 

  • Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ et al. (2006). Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 332, 752–760.

    Article  CAS  Google Scholar 

  • Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y et al. (2006). Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan public health center-based (JPHC) study cohort I. Circulation 113, 195–202.

    Article  CAS  Google Scholar 

  • Jump DB, Clarke SD (1999). Regulation of gene expression by dietary fat. Annu Rev Nutr 19, 63–90.

    Article  CAS  Google Scholar 

  • Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G (2003). Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 52, 1779–1785.

    Article  CAS  Google Scholar 

  • Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ et al. (2000). AHA dietary guidelines: revision 2000: a statement for healthcare professionals from the nutrition committee of the American heart association. Circulation 102, 2284–2299.

    Article  CAS  Google Scholar 

  • Kris-Etherton PM, Taylor DS, Yu-Poth S, Huth P, Moriarty K, Fishell V et al. (2000). Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 71, 179S–188S.

    Article  CAS  Google Scholar 

  • Kris-Etherton PM, Harris WS, Appel LJ (2002). Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 2747–2757.

    Article  Google Scholar 

  • Laville M, Rigalleau V, Riou JP, Beylot M (1995). Respective role of plasma nonesterified fatty acid oxidation and total lipid oxidation in lipid-induced insulin resistance. Metabolism 44, 639–644.

    Article  CAS  Google Scholar 

  • Lombardo YB, Chicco AG (2006). Effects of dietary polyunsaturated n−3 fatty acids on dyslipidemia and insulin resistance in rodents and humans: a review. J Nutr Biochem 17, 1–13.

    Article  CAS  Google Scholar 

  • Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A et al. (1991). Oral (n−3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 121, 547–555.

    Article  CAS  Google Scholar 

  • Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S et al. (2006). Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes 55, 924–928.

    Article  CAS  Google Scholar 

  • Nettleton JA, Katz R (2005). n−3 Long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc 105, 428–440.

    Article  CAS  Google Scholar 

  • Pai JK, Pischon T, Ma J, Manson JE, Hankinson SE, Joshipura K et al. (2004). Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med 351, 2599–2610.

    Article  CAS  Google Scholar 

  • Rabasa-Lhoret R, Bastard JP, Jan V, Ducluzeau PH, Andreelli F, Guebre F et al. (2003). Modified quantitative insulin sensitivity check index is better correlated to hyperinsulinemic glucose clamp than other fasting-based index of insulin sensitivity in different insulin-resistant states. J Clin Endocrinol Metab 88, 4917–4923.

    Article  CAS  Google Scholar 

  • Rivellese AA, Lilli S (2003). Quality of dietary fatty acids, insulin sensitivity and type 2 diabetes. Biomed Pharmacother 57, 84–87.

    Article  CAS  Google Scholar 

  • Rossi AS, Lombardo YB, Lacorte JM, Chicco AG, Rouault C, Slama G et al. (2005). Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats. Am J Physiol Regul Integr Comp Physiol 289, R486–R494.

    Article  CAS  Google Scholar 

  • Simopoulos AP (1999). Essential fatty acids in health and chronic disease. Am J Clin Nutr 70, 560S–569S.

    Article  CAS  Google Scholar 

  • Simopoulos AP, Robinson J (1999). The Omega Diet. The Lifesaving Nutritional Program Based on the Diet of the Island of Crete. HarperCollins: New York.

    Google Scholar 

  • Skilton MR, Celermajer DS (2006). The effects of obesity-related peptides on the vasculature. Curr Vasc Pharmacol 4, 79–85.

    Article  CAS  Google Scholar 

  • Summers LK, Fielding BA, Bradshaw HA, Ilic V, Beysen C, Clark ML et al. (2002). Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity. Diabetologia 45, 369–377.

    Article  CAS  Google Scholar 

  • Ukropec J, Reseland JE, Gasperikova D, Demcakova E, Madsen L, Berge RK et al. (2003). The hypotriglyceridemic effect of dietary n−3 FA is associated with increased beta-oxidation and reduced leptin expression. Lipids 38, 1023–1029.

    Article  CAS  Google Scholar 

  • Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE et al. (2001). Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86, 1930–1935.

    Article  CAS  Google Scholar 

  • Wigmore SJ, Fearon KC, Maingay JP, Ross JA (1997). Down-regulation of the acute-phase response in patients with pancreatic cancer cachexia receiving oral eicosapentaenoic acid is mediated via suppression of interleukin−6. Clin Sci (Lond) 92, 215–221.

    Article  CAS  Google Scholar 

  • Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S et al. (2002). Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8, 1288–1295.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Monique Sothier, Christine Maitrepierre, Jocelyne Peyrat and Corine Louche-Pellissier for their contribution to this work. We thank Beckman-Coulter France for the generous gift of antibodies for Hs-CRP measurement as well as P Chaumon and Centre d'éducation, recherche et information en nutrition (CERIN) for financial support and advice. This work was supported by a grant from Association de langue française pour l'étude du diabète et autre maladies métaboliques (ALFEDIAM-Servier) and Fondation pour la Recherche Médicale, France.

The editorial assistance of Ovid M Da Silva, Research Support Office, Research Centre, CHUM is also acknowledged.

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Correspondence to M Laville.

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Contributors: FG-E: Data collection/interpretation and manuscript. RR-L: Data collection/interpretation and manuscript. FB: Manuscript. J-PB: Data collection and manuscript revision. MD: Data collection and manuscript revision. MRS: Manuscript revision. HV: Study design and manuscript revision. ML: Study design and supervision, and manuscript revision.

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Guebre-Egziabher, F., Rabasa-Lhoret, R., Bonnet, F. et al. 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 62, 1287–1293 (2008). https://doi.org/10.1038/sj.ejcn.1602857

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