PMID- 31831363 OWN - NLM STAT- MEDLINE DCOM- 20200914 LR - 20200914 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 30 IP - 3 DP - 2020 Mar 9 TI - Effects of DHA-enriched fish oil on gene expression levels of p53 and NF-kappaB and PPAR-gamma activity in PBMCs of patients with T2DM: A randomized, double-blind, clinical trial. PG - 441-447 LID - S0939-4753(19)30411-9 [pii] LID - 10.1016/j.numecd.2019.10.012 [doi] AB - BACKGROUND AND AIMS: Omega-3 polyunsaturated fatty acids (PUFAs) are natural peroxisome proliferator-activated receptor gamma (PPAR-gamma) ligands. Activated PPAR-gamma protects the cardiovascular system against atherosclerotic lesion formation and exerts its anti-inflammatory role by suppressing cytokines induced by nuclear factor kappa-B (NF-kappaB) in endothelial cells (ECs), and it is hypothesized that apoptosis and cell cycle arrest induced by PPAR-gamma ligands may be mediated by the p53-dependent pathway. The aim of our study was to investigate the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on PPAR-gamma activity and mRNA expression levels of p53 and NF-kappaB. METHODS AND RESULTS: Fifty patients with type 2 diabetes mellitus (T2DM) aged 30-70 years were randomly assigned to receive either 2400 mg/d DHA-rich fish oil or placebo for 8 weeks. Metabolic parameters were assessed at baseline and at the end of the intervention. PPAR-gamma activity in the peripheral blood mononuclear cells (PBMCs) was measured using ELISA-based PPAR-gamma Transcription Factor Assay Kit, and the gene expression levels of p53 and NF-kappaB were assessed using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). On the basis of our finding, 8 weeks of treatment with DHA-rich fish oil increased PPAR-gamma activity in PBMCs of subjects with T2DM (p < 0.01) compared to that in placebo (p = 0.4). Between-group comparisons of mean PPAR-gamma activity changes showed significant differences (p = 0.03), whereas mRNA expression levels of the p53 and NF-kappaB genes did not show significant differences between studied groups (p = 0.2 and p = 0.5, respectively). CONCLUSION: Our findings indicated that short-term DHA-rich fish oil supplementation may modulate PPAR-gamma activity in PBMCs. CI - Copyright (c) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Naeini, Zeinab AU - Naeini Z AD - Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Toupchian, Omid AU - Toupchian O AD - Department of Nutrition and Public Health, School of Health, North Khorasan University of Medical Science, Bojnurd, Iran. FAU - Vatannejad, Akram AU - Vatannejad A AD - Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Iran; Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran. FAU - Sotoudeh, Gity AU - Sotoudeh G AD - Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. FAU - Teimouri, Maryam AU - Teimouri M AD - Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran. FAU - Ghorbani, Mostafa AU - Ghorbani M AD - Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. FAU - Nasli-Esfahani, Ensieh AU - Nasli-Esfahani E AD - Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Koohdani, Fariba AU - Koohdani F AD - Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: fkoohdan@tums.ac.ir. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191105 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (NF-kappa B) RN - 0 (PPAR gamma) RN - 0 (PPARG protein, human) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 25167-62-8 (Docosahexaenoic Acids) SB - IM MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/genetics MH - *Dietary Supplements/adverse effects MH - Docosahexaenoic Acids/*administration & dosage/adverse effects MH - Double-Blind Method MH - Female MH - Humans MH - Iran MH - Leukocytes, Mononuclear/*drug effects/metabolism MH - Male MH - Middle Aged MH - NF-kappa B/*blood/genetics MH - PPAR gamma/*blood MH - Time Factors MH - Treatment Outcome MH - Tumor Suppressor Protein p53/genetics/*metabolism OTO - NOTNLM OT - Atherosclerosis OT - Diabetes OT - Docosahexaenoic acid OT - Gene expression OT - Inflammation OT - PPAR-gamma COIS- Declaration of Competing Interest The authors have no relevant conflicts of interest to declare. EDAT- 2019/12/14 06:00 MHDA- 2020/09/15 06:00 CRDT- 2019/12/14 06:00 PHST- 2019/08/07 00:00 [received] PHST- 2019/10/26 00:00 [revised] PHST- 2019/10/29 00:00 [accepted] PHST- 2019/12/14 06:00 [pubmed] PHST- 2020/09/15 06:00 [medline] PHST- 2019/12/14 06:00 [entrez] AID - S0939-4753(19)30411-9 [pii] AID - 10.1016/j.numecd.2019.10.012 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2020 Mar 9;30(3):441-447. doi: 10.1016/j.numecd.2019.10.012. Epub 2019 Nov 5.