Omega-3 and Omega-6 Fatty Acids: Role in Body Fat Gain and Development of Obesity
Abstract
The ratio of ω6 to ω3 polyunsaturated fatty acid (PUFA) in western diet has remarkably increased over the past decades. This change in dietary fatty acid (FA) composition, independent of the total caloric intake and total fat intake, may contribute to the obesity epidemic in many populations. Experimental studies show that ω3 and ω6 FAs play different role in adipogenesis, lipid homeostasis, brain-gut-adipose axis signaling, and systemic inflammation, resulting in divergent effects on body fat growth. Evidence from human studies remains limited and inconclusive. Very few observational studies and clinical trials have examined the association between composition of PUFA, particularly ω6 FA and ω6/ω3 ratio, with obesity-specific parameters. A consensus on the optimal intake of ω3 and ω6 subtype FAs and ω6/ω3 ratio in diet is lacking. We reviewed the temporal change in dietary PUFA composition in US, experimental studies that examine the effects of ɷ3 and ω6 FAs on body fat, and epidemiologic studies that assess the association between dietary PUFAs and the development of obesity. Future studies need to further evaluate dietary FAs and their biomarkers in association with objective and longitudinal measurements of body fat and elucidate the potential role of diet with a balanced ω3 and ω6 FA composition in the primary prevention of obesity.
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Hooper L, Abdelhamid A, Moore HJ, Douthwaite W, Skeaff CM, Summerbell CD. Effect of reducing total fat intake on body weight: systematic review and meta-analysis of randomised controlled trials and cohort studies. BMJ. 2012;345:e7666.
Tremblay A. Dietary fat and body weight set point. Nutr Rev. 2004;62:S75-77.
Carmichael HE, Swinburn BA, Wilson MR. Lower fat intake as a predictor of initial and sustained weight loss in obese subjects consuming an otherwise ad libitum diet. J Am Diet Assoc. 1998 Jan;98:35-39.
Heitmann BL, Lissner L, Sorensen TI, Bengtsson C. Dietary fat intake and weight gain in women genetically predisposed for obesity. Am J Clin Nutr. 1995;61:1213-1217.
Lissner L, Heitmann BL, Bengtsson C. Low-fat diets may prevent weight gain in sedentary women: prospective observations from the population study of women in Gothenburg, Sweden. Obes Res. 1997 Jan;5:43-48.
Sherwood NE, Jeffery RW, French SA, Hannan PJ, Murray DM. Predictors of weight gain in the Pound of Prevention study. Int J Obes Relat Metab Disord. 2000;24:395-403.
Sheppard L, Kristal AR, Kushi LH. Weight loss in women participating in a randomized trial of low-fat diets. Am J Clin Nutr. 1991;54:821-828.
Westerterp-Plantenga MS, Wijckmans-Duijsens NE, Verboeket-van de Venne WP, de Graaf K, van het Hof KH, Weststrate JA. Energy intake and body weight effects of six months reduced or full fat diets, as a function of dietary restraint. Int J Obes Relat Metab Disord. 1998;22:14-22.
Rock CL, Thomson C, Caan BJ, Flatt SW, Newman V, Ritenbaugh C, Marshall JR, Hollenbach KA, Stefanick ML, Pierce JP. Reduction in fat intake is not associated with weight loss in most women after breast cancer diagnosis: evidence from a randomized controlled trial. Cancer. 2001;91:25-34.
Brehm BJ, Spang SE, Lattin BL, Seeley RJ, Daniels SR, D'Alessio DA. The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets. J Clin Endocrinol Metab. 2005;90:1475-1482.
Troiano RP, Briefel RR, Carroll MD, Bialostosky K. Energy and fat intakes of children and adolescents in the united states: data from the national health and nutrition examination surveys. Am J Clin Nutr. 2000;72:1343S-1353S.
Swan G. Findings from the latest National Diet and Nutrition Survey. Proc Nutr Soc. 2004;63:505-512.
Ailhaud G, Massiera F, Weill P, Legrand P, Alessandri JM, Guesnet P. Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity. Prog Lipid Res. 2006;45:203-236.
Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ.346:e8707.
Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999;70:560S-569S.
Fickova M, Hubert P, Cremel G, Leray C. Dietary (n-3) and (n-6) polyunsaturated fatty acids rapidly modify fatty acid composition and insulin effects in rat adipocytes. J Nutr. 1998;128:512-519.
Amri EZ, Ailhaud G, Grimaldi PA. Fatty acids as signal transducing molecules: involvement in the differentiation of preadipose to adipose cells. J Lipid Res. 1994;35:930-937.
Jump DB, Clarke SD, Thelen A, Liimatta M. Coordinate regulation of glycolytic and lipogenic gene expression by polyunsaturated fatty acids. J Lipid Res. 1994;35:1076-1084.
Clarke SD, Jump D. Polyunsaturated fatty acids regulate lipogenic and peroxisomal gene expression by independent mechanisms. Prostaglandins Leukot Essent Fatty Acids. 1997;57:65-69.
Schwinkendorf DR, Tsatsos NG, Gosnell BA, Mashek DG. Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism. Int J Obes (Lond).
;35:336-344.
James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty
acids and inflammatory mediator production. Am J Clin Nutr.
;71:343S-348S.
Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology
of obesity. Gastroenterology. 2007;132:2087-2102.
Rennie KL, Jebb SA. Prevalence of obesity in Great Britain. Obes Rev.
;6:11-12.
Cameron AJ, Welborn TA, Zimmet PZ, Dunstan DW, Owen N,
Salmon J, Dalton M, Jolley D, Shaw JE. Overweight and obesity in Australia: the 1999-2000 Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Med J Aust. 2003;178:427-432.
Yumuk VD. Prevalence of obesity in Turkey. Obes Rev. 2005;6:9-10.
Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-
JAMA. 2012;307:491-497.
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood
and adult obesity in the United States, 2011-2012. JAMA.
;311:806-814.
WHO Media centre. Obesity and overweight Fact sheet N°311, May
http://www.who.int/mediacentre/factsheets/fs311/en/ Accessed
/30/2013.
Caterson ID, Hubbard V, Bray GA, Grunstein R, Hansen BC, Hong Y,
Labarthe D, Seidell JC, Smith SC, Jr. Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease and stroke: Group III: worldwide comorbidities of obesity. Circulation. 2004;110:e476-483.
Weinstein AR, Sesso HD. Joint effects of physical activity and body weight on diabetes and cardiovascular disease. Exerc Sport Sci Rev. 2006;34:10-15.
Huang Z, Willett WC, Manson JE, et al. Body weight, weight change, and risk for hypertension in women. Ann Intern Med. 1998;128:81-88.
Samanic C, Chow WH, Gridley G, Jarvholm B, Fraumeni JF Jr. Relation of body mass index to cancer risk in 362,552 Swedish men. Cancer Causes Control. 2006;17:901-909.
Finkelstein EA, Ruhm CJ, Kosa KM. Economic causes and consequences of obesity. Annu Rev Public Health. 2005;26:239-257.
Finkelstein EA, Fiebelkorn IC, Wang G. National medical spending attributable to overweight and obesity: how much, and who's paying? Health Aff (Millwood). 2003;Suppl Web Exclusives:W3-219-26.
Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev. 1998;78:783-809.
Katan MB. Weight-loss diets for the prevention and treatment of obesity. N Engl J Med. 2009;360:923-925.
Romieu I, Willett WC, Stampfer MJ, et al. Energy intake and other determinants of relative weight. Am J Clin Nutr. 1988;47:406-412.
Nguyen VT, Larson DE, Johnson RK, Goran MI. Fat intake and
adiposity in children of lean and obese parents. Am J Clin Nutr.
;63:507-513.
Ailhaud G, Guesnet P, Cunnane SC. An emerging risk factor for
obesity: does disequilibrium of polyunsaturated fatty acid metabolism contribute to excessive adipose tissue development? Br J Nutr. 2008;100:461-470.
Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011;93:950- 962.
Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Bio Med (Marywood). 2008;233:674-688.
Simopoulos AP, Leaf A, Salem N, Jr. Essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. Ann Nutr Metab. 1999;43:127-30.
Hamazaki T, Okuyama H. The Japan Society for Lipid Nutrition recommends to reduce the intake of linoleic acid. A review and critique of the scientific evidence. World Rev Nutr Diet. 2003;92:109-132.
Harris WS, Mozaffarian D, Rimm E, et al. Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation. 2009;119:902-907.
Dietary fat and its relation to heart attacks and strokes. Report by the Central Committee for Medical and Community Program of the American Heart Association. JAMA. 1961;175:389-391.
Keys A. Effects of Different Dietary Fats on Plasma-Lipid Levels. Lancet. 1965;1:318-319.
Strum-Odin R, Adkins-Finke B, Blake WL, Phinney SD, Clarke SD. Modification of fatty acid composition of membrane phospholipid in hepatocyte monolayer with n-3, n-6 and n-9 fatty acids and its relationship to triacylglycerol production. Biochim Biophys Acta. 1987;921:378-391.
Hennig B, Watkins BA. Linoleic acid and linolenic acid: effect on permeability properties of cultured endothelial cell monolayers. Am J Clin Nutr. 1989;49:301-305.
Massiera F, Saint-Marc P, Seydoux J, et al. Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res. 2003;44:271-279.
Parrish CC, Pathy DA, Angel A. Dietary fish oils limit adipose tissue hypertrophy in rats. Metabolism. 1990;39:217-219.
Raclot T, Groscolas R, Langin D, Ferre P. Site-specific regulation of gene expression by n-3 polyunsaturated fatty acids in rat white adipose tissues. J Lipid Res. 1997;38:1963-1972.
Vassaux G, Gaillard D, Ailhaud G, Negrel R. Prostacyclin is a specific effector of adipose cell differentiation. Its dual role as a cAMP- and Ca(2+)-elevating agent. J Biol Chem. 1992;267:11092-11097.
Barak Y, Nelson MC, Ong ES, et al. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell. 1999;4:585-595.
Kubota N, Terauchi Y, Miki H, et al. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell. 1999;4:597-609.
Rosen ED, Hsu CH, Wang X, et al. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev. 2002;16:22-26.
Ren D, Collingwood TN, Rebar EJ, Wolffe AP, Camp HS. PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. Genes Dev. 2002;16:27-32.
Rosen ED, Sarraf P, Troy AE, et al. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell. 1999;4:611-617.
Gaillard D, Negrel R, Lagarde M, Ailhaud G. Requirement and role of arachidonic acid in the differentiation of pre-adipose cells. Biochem J. 1989;257:389-97.
Hihi AK, Michalik L, Wahli W. PPARs: transcriptional effectors of fatty acids and their derivatives. Cell Mol Life Sci. 2002;59:790-798.
Massaro M, Habib A, Lubrano L, et al. The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKC epsilon inhibition. Proc Natl Acad Sci U S A. 2006;103:15184-15189.
Ringbom T, Huss U, Stenholm A, Flock S, Skattebol L, Perera P, Bohlin L. Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001;64:745-749.
Corey EJ, Shih C, Cashman JR. Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis. Proc Natl Acad Sci U S A. 1983;80:3581-3584.
Mirnikjoo B, Brown SE, Kim HF, Marangell LB, Sweatt JD, Weeber EJ. Protein kinase inhibition by omega-3 fatty acids. J Biol Chem. 2001;276:10888-10896.
Silvestri C, Di Marzo V. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Cell Metab. 2013;17:475-490.
Di Marzo V. Endocannabinoids: synthesis and degradation. Rev Physiol Biochem Pharmacol. 2008;160:1-24.
Di Marzo V, Matias I. Endocannabinoid control of food intake and energy balance. Nat Neurosci. 2005;8:585-589.
Matias I, Bisogno T, Di Marzo V. Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake. Int J Obes (Lond). 2006;30 Suppl 1:S7-S12.
Batetta B, Griinari M, Carta G, et al. Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats. J Nutr. 2009;139:1495-1501.
Reidy SP, Weber J. Leptin: an essential regulator of lipid metabolism. Comp Biochem Physiol A Mol Integr Physiol. 2000;125:285-298.
Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV. Leptin:
the tale of an obesity gene. Diabetes. 1996;45:1455-1462.
Cha MC, Jones PJ. Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats. J Lipid Res. 1998;39:1655-1660.
Reseland JE, Haugen F, Hollung K, et al. Reduction of leptin gene expression by dietary polyunsaturated fatty acids. J Lipid Res. 2001;42:743-750.
Fan C, Liu X, Shen W, Deckelbaum RJ, Qi K. The Regulation of Leptin, Leptin Receptor and Pro-opiomelanocortin Expression by N-3 PUFAs in Diet-Induced Obese Mice Is Not Related to the Methylation of Their Promoters. Nutrition & metabolism. 2011;8:31.
Kratz M, von Eckardstein A, Fobker M, et al. The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women. J Clin Endocrinol Metab. 2002;87:5008-5014.
Iwaki M, Matsuda M, Maeda N, et al. Induction of adiponectin, a fat- derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes. 2003;52:1655-1663.
Goldstein BJ, Scalia R. Adiponectin: A novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab. 2004;89:2563-2568.
Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose- specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79-83.
Hardie DG, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Ann Rev Biochem. 1998;67:821-855.
Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol. 1999;277:E1-10.
Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP- activated protein kinase. Nat Med. 2002;8:1288-1295.
Flachs P, Mohamed-Ali V, Horakova O, et al. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia. 2006;49:394-397.
Neschen S, Morino K, Rossbacher JC, et al. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor- gamma-dependent mechanism in mice. Diabetes. 2006;55:924-928.
Banga A, Unal R, Tripathi P, et al. Adiponectin translation is increased by the PPARgamma agonists pioglitazone and omega-3 fatty acids. American journal of physiology Endocrinology and metabolism. 2009;296:E480-489.
Hernandez-Morante JJ, Milagro FI, Larque E, Lujan J, Martinez JA, Zamora S, Garaulet M. Relationship among adiponectin, adiponectin gene expression and fatty acids composition in morbidly obese patients. Obes Surg. 2007;17:516-524.
Fernandez-Real JM, Vendrell J, Ricart W. Circulating adiponectin and plasma fatty acid profile. Clin Chem. 2005;51:603-609.
Itoh M, Suganami T, Satoh N, et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arteriosclerosis, thrombosis, and vascular biology. 2007;27:1918-1925.
An WS, Son YK, Kim SE, et al. Association of adiponectin and leptin with serum lipids and erythrocyte omega-3 and omega-6 fatty acids in dialysis patients. Clinical nephrology. 2011;75:195-203.
Monk JM, Hou TY, Turk HF, et al. Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during colitis. PLoS One. 2012;7:e49739.
Kalupahana NS, Claycombe K, Newman SJ, et al. Eicosapentaenoic acid prevents and reverses insulin resistance in high-fat diet-induced obese mice via modulation of adipose tissue inflammation. J Nutr. 2010;140:1915-1922.
Hsueh HW, Zhou Z, Whelan J, et al. Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via Toll-like receptor-2-mediated pathways. J Nutr. 2011;141:1260-1266.
Itariu BK, Zeyda M, Hochbrugger EE, et al. Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial. Am J Clin Nutr. 2012;96:1137-1149.
Tsitouras PD, Gucciardo F, Salbe AD, Heward C, Harman SM. High omega-3 fat intake improves insulin sensitivity and reduces CRP and IL6, but does not affect other endocrine axes in healthy older adults. Horm Metab Res. 2008;40:199-205.
Zhao G, Etherton TD, Martin KR, Gillies PJ, West SG, Kris-Etherton PM. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr. 2007;85:385-391.
Spencer M, Finlin BS, Unal R, et al. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes. 2013;62:1709-1717.
Lepperdinger G. Inflammation and mesenchymal stem cell aging. Curr Opin Immunol. 2011;23:518-524.
Wu JH, Micha R, Imamura F, et al. Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. Br J Nutr. 2012;107(Suppl 2):S214-227.
Wallin A, Di Giuseppe D, Orsini N, Patel PS, Forouhi NG, Wolk A. Fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes: systematic review and meta-analysis of prospective studies. Diabetes Care. 2012;35:918-929.
Xun P, He K. Fish Consumption and Incidence of Diabetes: meta- analysis of data from 438,000 individuals in 12 independent prospective cohorts with an average 11-year follow-up. Diabetes Care. 2012;35:930-938.
Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV. The relation between insulin sensitivity and the fatty- acid composition of skeletal-muscle phospholipids. N Engl J Med. 1993;328:238-244.
Pan DA, Lillioja S, Milner MR, et al. Skeletal muscle membrane lipid composition is related to adiposity and insulin action. J Clin Invest. 1995;96:2802-2808.
Rodriguez Y, Christophe AB. Long-chain omega6 polyunsaturated fatty acids in erythrocyte phospholipids are associated with insulin resistance in non-obese type 2 diabetics. Clin Chim Acta. 2005;354:195-199.
Vessby B, Aro A, Skarfors E, Berglund L, Salminen I, Lithell H. The risk to develop NIDDM is related to the fatty acid composition of the serum cholesterol esters. Diabetes. 1994;43:1353-1357.
Wang L, Folsom AR, Zheng ZJ, Pankow JS, Eckfeldt JH, Investigators AS. Plasma fatty acid composition and incidence of diabetes in middle- aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr. 2003;78:91-98.
Field AE, Willett WC, Lissner L, Colditz GA. Dietary fat and weight gain among women in the Nurses' Health Study. Obesity (Silver Spring). 2007;15:967-976.
Koh-Banerjee P, Chu NF, Spiegelman D, et al. Prospective study of the association of changes in dietary intake, physical activity, alcohol consumption, and smoking with 9-y gain in waist circumference among 16 587 US men. Am J Clin Nutr. 2003;78:719-727.
Wang L, Manson JE, Rautiainen S, et al. A prospective study of erythrocyte polyunsaturated fatty acid, weight gain, and risk of becoming overweight or obese in middle-aged and older women. European journal of nutrition. 2015.
Couet C, Delarue J, Ritz P, Antoine JM, Lamisse F. Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes Relat Metab Disord. 1997;21:637-643.
Krebs JD, Browning LM, McLean NK, et al. Additive benefits of long- chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women. Int J Obes (Lond). 2006;30:1535-1544.
Thorsdottir I, Tomasson H, Gunnarsdottir I, et al. Randomized trial of weight-loss-diets for young adults varying in fish and fish oil content. Int J Obes (Lond). 2007;31:1560-1566.
Kunesova M, Braunerova R, Hlavaty P, et al. The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short- term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women. Physiol Res. 2006;55:63-72.
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. 2008;62:1287-1293.
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