title: Dietary omega-3 fatty acid deficiency and high fructose intake in the development of metabolic syndrome, brain metabolic abnormalities, and non-alcoholic fatty liver disease.
abstract: Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS). Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD), promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health.
authors.affiliation: The Center for Genetics, Nutrition and Health, 2001 S Street, NW, Suite 530, Washington, DC 20009, USA. cgnh@bellatlantic.net
authors.forename: Artemis P
authors.initials: AP
authors.lastname: Simopoulos
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood*; D005234:Fatty Liver / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D005395:Fish Oils / Q000008:administration & dosage; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D065626:Non-alcoholic Fatty Liver Disease; D013549:Sweetening Agents / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007328:Insulin; D013549:Sweetening Agents; D005632:Fructose
references.citation: Physiol Rev. 2010 Jan;90(1):23-46
references.pmid: 20086073
references.citation: Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2060-7
references.pmid: 22895667
references.citation: J Comp Neurol. 2005 Dec 5;493(1):63-71
references.pmid: 16254991
references.citation: N Engl J Med. 1989 Mar 16;320(11):733-4
references.pmid: 2646538
references.citation: Annu Rev Public Health. 2010;31:53-68
references.pmid: 20070200
references.citation: Am J Psychiatry. 2006 Jun;163(6):969-78
references.pmid: 16741195
references.citation: J Nutrigenet Nutrigenomics. 2011;4(2):65-8
references.pmid: 21613791
references.citation: Eur J Nutr. 2005 Jun;44(4):250-4
references.pmid: 15309420
references.citation: Annu Rev Physiol. 2008;70:513-35
references.pmid: 17988209
references.citation: Cell Mol Life Sci. 2012 Mar;69(5):741-62
references.pmid: 21997383
references.citation: J Clin Invest. 2005 May;115(5):1298-305
references.pmid: 15864349
references.citation: PLoS Biol. 2011 Jul;9(7):e1001116
references.pmid: 21814494
references.citation: Am J Clin Nutr. 2011 Jul;94(1):112-9
references.pmid: 21613559
references.citation: Free Radic Biol Med. 1994 Oct;17(4):367-72
references.pmid: 8001841
references.citation: Crit Rev Food Sci Nutr. 2010 Jan;50(1):1-19
references.pmid: 20047137
references.citation: Cell Metab. 2009 Jan 7;9(1):35-51
references.pmid: 19117545
references.citation: Neuroendocrinology. 2011;93(3):143-9
references.pmid: 21372559
references.citation: J Clin Invest. 1995 Dec;96(6):2735-43
references.pmid: 8675642
references.citation: Am J Clin Nutr. 2003 Oct;78(4):873S-880S
references.pmid: 14522752
references.citation: FASEB J. 2009 Jun;23(6):1946-57
references.pmid: 19211925
references.citation: Obesity (Silver Spring). 2009 Oct;17(10):1861-5
references.pmid: 19543218
references.citation: Neurosci Biobehav Rev. 2007;31(7):1046-63
references.pmid: 17544131
references.citation: Hepatology. 2003 Dec;38(6):1529-39
references.pmid: 14647064
references.citation: Biol Psychiatry. 2005 Aug 1;58(3):175-89
references.pmid: 16084838
references.citation: Nature. 2006 Dec 14;444(7121):854-9
references.pmid: 17167473
references.citation: Nat Neurosci. 2005 May;8(5):579-84
references.pmid: 15856066
references.citation: Diabetes Care. 2013 Jan;36(1):150-6
references.pmid: 22933433
references.citation: Am J Clin Nutr. 1993 Nov;58(5 Suppl):796S-799S
references.pmid: 8213612
references.citation: Curr Opin Clin Nutr Metab Care. 2012 Jul;15(4):357-61
references.pmid: 22617566
references.citation: Br J Nutr. 2013 May;109(9):1573-89
references.pmid: 23433235
references.citation: Gastroenterology. 2002 Nov;123(5):1705-25
references.pmid: 12404245
references.citation: Global Health. 2008 Feb 26;4:4
references.pmid: 18302739
references.citation: Biochem Pharmacol. 2012 Sep 15;84(6):737-45
references.pmid: 22634336
references.citation: J Nutr. 2008 Jun;138(6):1039-46
references.pmid: 18492831
references.citation: N Engl J Med. 2002 Apr 18;346(16):1221-31
references.pmid: 11961152
references.citation: N Engl J Med. 1993 Jan 28;328(4):238-44
references.pmid: 8418404
references.citation: Clin Nutr. 2011 Feb;30(1):6-19
references.pmid: 20619513
references.citation: J Nutr Metab. 2010;2010:
references.pmid: 20700405
references.citation: J Diabetes. 2010 Sep;2(3):180-93
references.pmid: 20923483
references.citation: Crit Rev Food Sci Nutr. 2010 Nov;50(10):889-918
references.pmid: 21108071
references.citation: Nat Neurosci. 2005 May;8(5):571-8
references.pmid: 15856065
references.citation: Annu Rev Physiol. 2008;70:537-56
references.pmid: 17937601
references.citation: JAMA. 2013 Jan 2;309(1):63-70
references.pmid: 23280226
references.citation: Nat Cell Biol. 2011 Mar;13(3):184-90
references.pmid: 21364565
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2939-44
references.pmid: 21282643
references.citation: JAMA. 2004 Aug 25;292(8):927-34
references.pmid: 15328324
references.citation: Am J Public Health. 2007 Apr;97(4):667-75
references.pmid: 17329656
references.citation: Am J Clin Nutr. 2009 May;89(5):1299-306
references.pmid: 19339405
references.citation: Am J Cardiol. 2006 Aug 21;98(4A):27i-33i
references.pmid: 16919514
references.citation: Horm Res. 2007;68(2):72-82
references.pmid: 17344645
references.citation: Aging (Albany NY). 2012 Feb;4(2):98-115
references.pmid: 22328600
references.citation: Panminerva Med. 2012 Sep;54(3):171-8
references.pmid: 22801434
references.citation: J Am Coll Nutr. 2002 Dec;21(6):495-505
references.pmid: 12480795
references.citation: Lancet. 2007 Nov 17;370(9600):1706-13
references.pmid: 18022033
references.citation: Obes Res. 2005 Jul;13(7):1146-56
references.pmid: 16076983
references.citation: Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):187-93
references.pmid: 18991793
references.citation: Obesity (Silver Spring). 2012 Oct;20(10):1984-94
references.pmid: 22334255
references.citation: Am J Clin Nutr. 2011 May;93(5):950-62
references.pmid: 21367944
references.citation: Arch Intern Med. 2008 Jul 28;168(14):1487-92
references.pmid: 18663160
references.citation: J Clin Endocrinol Metab. 2011 Oct;96(10):E1596-605
references.pmid: 21849529
references.citation: Nat Med. 2004 Jun;10(6):563-9
references.pmid: 15170194
references.citation: World Rev Nutr Diet. 2001;88:18-27
references.pmid: 11935953
references.citation: Brain Res Mol Brain Res. 2004 May 19;124(2):134-42
references.pmid: 15135221
references.citation: Science. 2006 May 12;312(5775):861-4
references.pmid: 16690851
references.citation: Prog Lipid Res. 2001 Jan-Mar;40(1-2):1-94
references.pmid: 11137568
references.citation: J Biol Chem. 2003 Sep 19;278(38):35931-9
references.pmid: 12853447
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2098-105
references.pmid: 16172216
references.citation: J Clin Invest. 2000 Jul;106(2):171-6
references.pmid: 10903330
references.citation: Biochim Biophys Acta. 2009 Nov;1792(11):1080-6
references.pmid: 19733654
references.citation: J Nutr. 2002 Nov;132(11):3333-9
references.pmid: 12421847
references.citation: Curr Opin Lipidol. 2008 Jun;19(3):242-7
references.pmid: 18460914
references.citation: Diabetes. 1991 Feb;40(2):280-9
references.pmid: 1991575
references.citation: Int J Mol Med. 2006 Dec;18(6):1047-55
references.pmid: 17089007
references.citation: Neuroimage. 2004 Dec;23(4):1486-93
references.pmid: 15589112
references.citation: Circulation. 2009 Sep 15;120(11):1011-20
references.pmid: 19704096
references.citation: Br J Nutr. 2011 Jul;106(1):79-86
references.pmid: 21396140
references.citation: Cell. 2008 Oct 3;135(1):61-73
references.pmid: 18854155
references.citation: Ann N Y Acad Sci. 2010 Nov;1212:97-113
references.pmid: 21070248
references.citation: Endocr Rev. 2006 Feb;27(1):73-100
references.pmid: 16306385
references.citation: J Pediatr. 2009 Jun;154(6):807-13
references.pmid: 19375714
references.citation: Arch Intern Med. 1993 Jun 28;153(12):1429-38
references.pmid: 8141868
references.citation: Physiol Behav. 2010 Apr 26;100(1):47-54
references.pmid: 20138901
references.citation: J Physiol. 2012 May 15;590(10):2485-99
references.pmid: 22473784
references.citation: Am J Clin Nutr. 2000 Feb;71(2):412-33
references.pmid: 10648253
references.citation: BMC Physiol. 2008 Dec 01;8:21
references.pmid: 19046413
references.citation: Crit Rev Food Sci Nutr. 2010 Jan;50(1):53-84
references.pmid: 20047139
references.citation: Exp Biol Med (Maywood). 2008 Jun;233(6):674-88
references.pmid: 18408140
references.citation: PLoS One. 2011;6(8):e23365
references.pmid: 21853118
references.citation: J Nutr. 2007 Sep;137(9):2121-7
references.pmid: 17709452
references.citation: Eur J Clin Invest. 1998 Apr;28(4):329-33
references.pmid: 9615913
references.citation: J Nutr. 2007 Jun;137(6):1447-54
references.pmid: 17513405
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2963-72
references.pmid: 15181085
references.citation: Am J Clin Nutr. 1991 Sep;54(3):438-63
references.pmid: 1908631
references.citation: Obesity (Silver Spring). 2013 Apr;21(4):782-5
references.pmid: 23512506
references.citation: World Rev Nutr Diet. 2009;99:VII-XII
references.pmid: 19230285
references.citation: Am J Clin Nutr. 2006 Dec;84(6):1374-9
references.pmid: 17158419
references.citation: Am J Clin Nutr. 2005 Oct;82(4):721-32
references.pmid: 16210699
references.citation: Physiol Behav. 2007 Sep 10;92(1-2):263-71
references.pmid: 17586536
references.citation: Am J Clin Nutr. 2012 Oct;96(4):727-34
references.pmid: 22952180
references.citation: J Nutr. 2012 Mar;142(3):600S-604S
references.pmid: 22279144
references.citation: Cell. 2007 Apr 20;129(2):251-62
references.pmid: 17448988
references.citation: Nature. 2001 Apr 12;410(6830):822-5
references.pmid: 11298451
references.citation: Prog Lipid Res. 2008 Mar;47(2):147-55
references.pmid: 18198131
references.citation: Nature. 2006 Sep 21;443(7109):289-95
references.pmid: 16988703
references.citation: Am J Clin Nutr. 2007 Jun;85(6):1511-20
references.pmid: 17556686
references.citation: J Hepatol. 2007 Nov;47(5):711-7
references.pmid: 17850914
references.citation: Br J Nutr. 2007 Oct;98 Suppl 1:S41-5
references.pmid: 17922958
references.citation: Am J Clin Nutr. 2009 Apr;89(4):1037-42
references.pmid: 19211821
references.citation: Nutrients. 2013 Feb 05;5(2):411-23
references.pmid: 23385371
references.citation: Curr Opin Lipidol. 2012 Feb;23(1):30-4
references.pmid: 22186661
references.citation: Hypertension. 1991 Nov;18(5):636-9
references.pmid: 1937667
references.citation: Experientia. 1976 Mar 15;32(3):373-4
references.pmid: 1253916
references.citation: Cell Metab. 2005 Jan;1(1):15-25
references.pmid: 16054041
references.citation: Diabetes. 1988 Dec;37(12):1595-607
references.pmid: 3056758
references.citation: Nat Neurosci. 2011 Mar;14(3):345-50
references.pmid: 21278728
references.citation: Endocr Rev. 2006 Oct;27(6):606-20
references.pmid: 16788162
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R603-11
references.pmid: 17553848
references.citation: Endocrinology. 2004 Feb;145(2):548-55
references.pmid: 14576175
references.citation: Physiol Behav. 2002 Jul;76(3):365-77
references.pmid: 12117573
references.citation: World Rev Nutr Diet. 2011;102:1-5
references.pmid: 21865813
references.citation: J Clin Invest. 2009 May;119(5):1322-34
references.pmid: 19381015
references.citation: Neuroscience. 2010 Nov 10;170(4):1035-44
references.pmid: 20709159