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      Association of Vitamin B12 with Pro-Inflammatory Cytokines and Biochemical Markers Related to Cardiometabolic Risk in Saudi Subjects

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          Abstract

          Background: This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population. Methods: A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m 2 and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m 2) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer. Results: Vitamin B12 was negatively associated with TNF-α (r = −0.14, p < 0.05), insulin (r = −0.230, p < 0.01) and HOMA-IR (r = −0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = −0.160, p < 0.01), insulin (r = −0.248, p < 0.01), HOMA-IR (r = −0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = −0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r 2 = −0.17, p < 0.05) and in children (r 2 = −0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r 2 = −0.78, p < 0.05). Conclusions: Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.

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          Most cited references30

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          Resistin, an adipokine with potent proinflammatory properties.

          The adipokine resistin is suggested to be an important link between obesity and insulin resistance. In the present study, we assessed the impact of resistin as inflammatogenic cytokine in the setting of arthritis. In vitro experiments on human PBMC were performed to assess cytokine response and transcription pathways of resistin-induced inflammation. Proinflammatory properties of resistin were evaluated in animal model by intra-articular injection of resistin followed by histological evaluation of the joint. Levels of resistin were assessed by ELISA in 74 paired blood and synovial fluid samples of patients with rheumatoid arthritis. Results were compared with the control group comprised blood samples from 34 healthy individuals and 21 synovial fluids from patients with noninflammatory joint diseases. We now show that resistin displays potent proinflammatory properties by 1) strongly up-regulating IL-6 and TNF-alpha, 2) responding to TNF-alpha challenge, 3) enhancing its own activity by a positive feedback, and finally 4) inducing arthritis when injected into healthy mouse joints. Proinflammatory properties of resistin were abrogated by NF-kappaB inhibitor indicating the importance of NF-kappaB signaling pathway for resistin-induced inflammation. Resistin is also shown to specifically accumulate in the inflamed joints of patients with rheumatoid arthritis and its levels correlate with other markers of inflammation. Our results indicate that resistin is a new and important member of the cytokine family with potent regulatory functions. Importantly, the identified properties of resistin make it a novel and interesting therapeutic target in chronic inflammatory diseases such as rheumatoid arthritis.
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            The role of resistin as a regulator of inflammation: Implications for various human pathologies.

            Resistin was originally described as an adipocyte-secreted peptide that induced insulin resistance in rodents. Increasing evidence indicates its important regulatory roles in various biological processes, including several inflammatory diseases. Further studies have shown that resistin in humans, in contrast to its production by adipocytes in mice, is synthesized predominantly by mononuclear cells both within and outside adipose tissue. Possible roles for resistin in obesity-related subclinical inflammation, atherosclerosis and cardiovascular disease, non-alcoholic fatty liver disease, rheumatic diseases, malignant tumors, asthma, inflammatory bowel disease, and chronic kidney disease have already been demonstrated. In addition, resistin can modulate several molecular pathways involved in metabolic, inflammatory, and autoimmune diseases. In this review, current knowledge about the functions and pathophysiological implications of resistin in different human pathologies is summarized, although there is a significant lack of firm evidence regarding the specific role resistin plays in the "orchestra" of the numerous mediators of inflammation.
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              Homocysteine-Induced Endothelial Dysfunction

              This review discussed and in particular emphasis the potential cellular pathways and the biological processes involved that lead to homocysteine-induced endothelial dysfunction, in particular in the impaired endothelial dependent dilatation aspect. Hyperhomocysteinemia is an independent cardiovascular risk factor that has been associated with atherosclerotic vascular diseases and ischemic heart attacks. The potential mechanisms by which elevated plasma homocysteine level leads to reduction in nitric oxide bioavailability include the disruptive uncoupling of nitric oxide synthase activity and quenching of nitric oxide by oxidative stress, the enzymatic inhibition by asymmetric dimethylarginine, endoplasmic reticulum stress with eventual endothelial cell apoptosis, and chronic inflammation/prothrombotic conditions. Homocysteine-induced endothelial dysfunction presumably affecting the bioavailability of the potent vasodilator ‘nitric oxide', and such dysfunction can easily be monitor by flow-mediated dilation method using ultrasound. Understanding the mechanisms by which plasma homocysteine alter endothelial nitric oxide production is therefore essential in the comprehension of homocysteine-induced impairment of endothelial dependent dilatation, and its association of cardiovascular risk and its pathophysiology.

                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                06 September 2016
                September 2016
                : 8
                : 9
                : 460
                Affiliations
                [1 ]Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; shakilhamdard@ 123456gmail.com (S.R.); eaglescout01@ 123456yahoo.com (S.S.); sobhy.yakout@ 123456gmail.com (S.Y.); wani.kaiser@ 123456gmail.com (K.W.); omrattas@ 123456ksu.edu.sa (O.S.A.-A.); g.tripathi@ 123456warwick.ac.uk (G.T.); msa85@ 123456yahoo.co.uk (M.S.A.)
                [2 ]Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
                [3 ]Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; p.saravanan@ 123456warwick.ac.uk
                [4 ]Division of Biomedical Sciences, Warwick Medical School, University of Warwick, UHCW Trust, Clifford Bridge Road, Walsgrave, Coventry CV2 2DX, UK; p.g.mcternan@ 123456warwick.ac.uk
                [5 ]Department of Biomedical Sciences, University of Westminster, London W1W 6UW, UK
                Author notes
                [* ]Correspondence: aldaghri2011@ 123456gmail.com ; Tel.: +966-11-4675939
                Article
                nutrients-08-00460
                10.3390/nu8090460
                5037505
                27608037
                91cd944e-79d4-4332-bc05-e2ceb68b9ee1
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 June 2016
                : 30 August 2016
                Categories
                Article

                Nutrition & Dietetics
                vitamin b12,resistin,tnf-α,cardiometabolic diseases
                Nutrition & Dietetics
                vitamin b12, resistin, tnf-α, cardiometabolic diseases

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