Down-regulation of NF-κB expression by n-3 fatty acid-rich linseed oil is modulated by PPARγ activation, eicosanoid cascade and secretion of cytokines by macrophages in rats fed partially hydrogenated vegetable fat.

Publisher: Steinkopff Country of Publication: Germany NLM ID: 100888704 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1436-6215 (Electronic) Linking ISSN: 14366207 NLM ISO Abbreviation: Eur J Nutr Subsets: MEDLINE

Original Publication: Darmstadt, Germany : Steinkopff, 1999-

Eicosanoids/*pharmacology ; Fatty Acids, Omega-3/*pharmacology ; Linseed Oil/*pharmacology ; Macrophages/*drug effects ; NF-kappa B/*metabolism ; PPAR gamma/*metabolism; 5-Lipoxygenase-Activating Proteins/genetics ; 5-Lipoxygenase-Activating Proteins/metabolism ; Animals ; Cells, Cultured ; Cholesterol/blood ; Cyclooxygenase 2/genetics ; Cyclooxygenase 2/metabolism ; Cytokines/blood ; Cytokines/metabolism ; Diet ; Down-Regulation ; Fatty Acids/analysis ; Macrophages/metabolism ; Male ; NF-kappa B/genetics ; PPAR gamma/genetics ; Rats ; Rats, Wistar ; Triglycerides/blood ; Up-Regulation

Purpose: The industrially produced partially hydrogenated vegetable fat (PHVF) contains trans fatty acid mostly comprising of elaidic acid (18:1 ∆9t). PHVF is used as a cooking medium in Southeast Asian countries. The purpose of this study is to evaluate the effects of dietary PHVF on inflammatory mediators and possible ameliorative effects of n-3 fatty acid (α-linolenic acid, ALA)-rich linseed oil (LSO) on the inflammatory mediators.
Methods: Male Wistar weaning rats were fed AIN-93-purified diet supplemented with one of the following lipids for 60 days, groundnut oil (GNO, 10 wt%), PHVF (10 wt%), LSO (10 wt%), PHVF blended with LSO at 2.5, 5.0 and 7.5 wt% levels. The final fat level in the diet was maintained at 10 wt%.
Results: The macrophages from rats fed PHVF showed higher levels of total cholesterol and free cholesterol as compared to those from rats fed GNO and LSO. Macrophages from rats fed PHVF down-regulated the expression of PPARγ and up-regulated the expressions of cytosolic phospholipase A 2 , cyclooxygenase-2, 5-lipoxygenase and nuclear factor-kappa B p65. The macrophages from rats fed PHVF secreted higher levels of pro-inflammatory eicosanoids and cytokines. The rats fed PHVF blended with LSO at incremental amounts showed a significant reduction in the expressions of pro-inflammatory markers in dose-dependent manner.
Conclusion: Detrimental effects of dietary PHVF in enhancing pro-inflammatory agents in rats could be significantly reduced by providing ALA (n-3 PUFA)-rich LSO.

Biochemistry. 2005 Mar 22;44(11):4458-65. (PMID: 15766276)
Nutrients. 2010 Mar;2(3):355-74. (PMID: 22254027)
J Nutr. 2010 Oct;140(10):1714-21. (PMID: 20724486)
J Lipid Res. 1964 Oct;5:600-8. (PMID: 14221106)
Mol Cell Biochem. 1997 Jan;166(1-2):135-43. (PMID: 9046030)
Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2220-6. (PMID: 21963840)
J Food Sci Technol. 2015 Oct;52(10 ):6395-404. (PMID: 26396384)
Nature. 2000 May 25;405(6785):421-4. (PMID: 10839530)
J Lipid Res. 2004 Feb;45(2):308-16. (PMID: 14563831)
N Engl J Med. 1990 Aug 16;323(7):439-45. (PMID: 2374566)
Adv Biol Regul. 2014 Jan;54:99-110. (PMID: 24113376)
Anal Biochem. 1984 Nov 1;142(2):347-50. (PMID: 6528973)
Annu Rev Nutr. 2006;26:45-73. (PMID: 16848700)
Indian J Exp Biol. 2014 Sep;52(9):860-9. (PMID: 25241585)
Immunol Cell Biol. 2000 Feb;78(1):31-9. (PMID: 10651927)
Circ Res. 2010 May 28;106(10):1559-69. (PMID: 20508200)
Nutrition. 2009 Jul-Aug;25(7-8):782-9. (PMID: 19251397)
J Immunol. 1988 Apr 1;140(7):2350-5. (PMID: 3127464)
Anal Biochem. 1985 Feb 1;144(2):417-22. (PMID: 2986478)
Annu Rev Cell Dev Biol. 2004;20:455-80. (PMID: 15473848)
Physiol Rev. 2012 Apr;92(2):739-89. (PMID: 22535896)
Biochim Biophys Acta. 1994 Nov 10;1224(2):255-63. (PMID: 7981240)
Can J Biochem Physiol. 1959 Aug;37(8):911-7. (PMID: 13671378)
Mediators Inflamm. 2013;2013:137579. (PMID: 23509418)
Br J Nutr. 2008 Apr;99(4):723-31. (PMID: 17925051)
J Biol Chem. 1951 Nov;193(1):265-75. (PMID: 14907713)
Biochim Biophys Acta. 2012 Feb;1821(2):303-12. (PMID: 22074701)
Mol Cell Biochem. 2005 Dec;280(1-2):9-16. (PMID: 16311900)
J Nutr. 1993 Nov;123(11):1939-51. (PMID: 8229312)
Biochim Biophys Acta. 1990 Feb 6;1042(2):265-7. (PMID: 2302426)
Sci Rep. 2014 May 21;4:5005. (PMID: 24845659)

Keywords: Elaidic acid; Inflammatory mediators; Linseed oil; Macrophages; Partially hydrogenated vegetable fat; α-Linolenic acid

0 (5-Lipoxygenase-Activating Proteins)
0 (Alox5ap protein, rat)
0 (Cytokines)
0 (Eicosanoids)
0 (Fatty Acids)
0 (Fatty Acids, Omega-3)
0 (NF-kappa B)
0 (PPAR gamma)
0 (Triglycerides)
8001-26-1 (Linseed Oil)
97C5T2UQ7J (Cholesterol)
EC 1.14.99.1 (Cyclooxygenase 2)
EC 1.14.99.1 (Ptgs2 protein, rat)

Date Created: 20160203 Date Completed: 20170825 Latest Revision: 20190905

20250114

10.1007/s00394-016-1163-7

26830417