Gene expression after dietary intervention with trans fatty acids (trans-11/trans-12 18:1) in humans

2009 ◽  
Vol 111 (5) ◽  
pp. 442-450 ◽  
Author(s):  
Katrin Kuhnt ◽  
Silke Flotho ◽  
Sailas Benjamin ◽  
Torsten Boerchers ◽  
Rainer Schubert ◽  
...  
Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3277-3277
Author(s):  
Lisa J Robinson ◽  
Janelle Zacherl ◽  
Harry C Blair ◽  
Stephanie J Mihalik

Abstract Abstract 3277 In recent decades, addition to the diet of synthetically hydrogenated vegetable oils has markedly increased human consumption of trans fatty acids. Epidemiological studies have linked this change in diet to current high rates of atherosclerotic cardiovascular disease. Despite recognition of this important connection, the basic mechanisms by which trans fatty acids contribute to the pathogenesis of atherosclerosis are still not well understood. In the present studies we examined the effects of trans fatty acids on macrophage functions and their possible role in the pathogenesis of atherosclerosis. Human macrophages, derived from peripheral blood mononuclear cells, were treated with the trans fat elaidic acid (C18:Δ9–10 trans), the corresponding cis fatty acid oleic acid (C18:Δ9–10 cis), or the saturated fatty acid stearic acid (C18:0). We examined changes in macrophage fat metabolism using GC/MS to measure cell fatty acid content and intermediates, and MS/MS to identify acylcarnitine derivatives, and assayed fatty acid oxidation using fatty acids radiolabeled at the [1–14C] position and the double bond at the [C9-C103H] position. After 44 hours treatment with 100 micromolar elaidic acid, macrophages showed an accumulation of multiple unsaturated fatty acid intermediates, both long-chain and short-chain, by GC/MS analysis, that were not observed in cultures containing either oleic or stearic acid. Using acylcarnitine analysis, we observed an increase in C12 and C18 intermediates in the macrophages exposed to trans fat (either as fatty acids or partially hydrogenated soy oil) compared to controls. These results suggest a block in acyl-CoA removal one group proximate to the trans bond. Beta-oxidation assays using carbon-1 radiolabeled oleic and elaidic acids revealed enhanced entry of the trans-fat into the catabolic cycle compared to the entry of the natural cis-fatty acid. Using carbon 9–10 radiolabeled oleic acid to study oleic acid catabolism, we discovered that in the presence of the trans fat, oxidation of the cis fat was diminished. Thus, in addition to the block in the catabolism of the trans fat itself, the degradation of the cis monounsaturated fatty acids are also impaired in the presence of the trans fat. We then examined the effects of inhibited fatty acid catabolism on macrophage function by examining changes in gene expression. Initial results from Affymetrix gene expression profiling, were confirmed using quantitative real time PCR. These studies revealed that exposure to trans fatty acid, compared to cis fatty acids, markedly upregulated macrophage expression of interleukin 1 beta, an inflammatory cytokine previously implicated in the pathogenesis of atherosclerosis. Also increased was expression of heparin-binding epidermal growth factor, previously implicated as a stimulus for vascular smooth muscle proliferation in atherosclerosis. The results overall suggest that the deleterious effects of trans fats may be linked to impaired macrophage fatty acid catabolism, contributing to lipid accumulation in the atheroma, and also to increased macrophage production of inflammatory mediators. Disclosures: No relevant conflicts of interest to declare.


Life Sciences ◽  
2019 ◽  
Vol 232 ◽  
pp. 116603 ◽  
Author(s):  
Reggiani V. Gonçalves ◽  
Jamili D.B. Santos ◽  
Natanny S. Silva ◽  
Etienne Guillocheau ◽  
Robson E. Silva ◽  
...  

2016 ◽  
Vol 25 ◽  
pp. 14-24 ◽  
Author(s):  
Wei-Lun Hung ◽  
Lucy Sun Hwang ◽  
Fereidoon Shahidi ◽  
Min-Hsiung Pan ◽  
Yu Wang ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246022
Author(s):  
Richard Molnar ◽  
Laszlo Szabo ◽  
Andras Tomesz ◽  
Arpad Deutsch ◽  
Richard Darago ◽  
...  

Both the intake of beneficial olive oil and of harmful trans-fatty acids (TFAs) in consumed foods are of great significance in tumor biology. In our present study we examined the effects they exert on the expression patterns of miR-134, miR-132, miR-124-1, miR-9-3 and mTOR in the liver, spleen and kidney of mice treated with 7,12-dimethylbenz [a] anthracene (DMBA). Feeding of TFA-containing diet significantly increased the expression of all studied miRs and mTORC1 in all organs examined, except the expression of mTORC1 in the spleen and kidney. Diet containing olive oil significantly reduced the expression of miR-124-1, miR-9-3 and mTORC1 in the liver and spleen. In the kidney, apart from the mTORC1 gene, the expression of all miRs examined significantly decreased compared to the DMBA control. According to our results, the cell membrane protective, antioxidant, and anti-inflammatory effects of olive oil and the cell membrane damaging, inflammatory, and carcinogenic properties of TFA suggest negative feedback regulatory mechanisms. In contrast to our expectations, mTORC1 gene expression in the kidney has not been shown to be an appropriate biomarker–presumably, because the many complex effects that regulate mTOR expression may quench each other.


Lipids ◽  
2017 ◽  
Vol 52 (4) ◽  
pp. 315-325 ◽  
Author(s):  
Marine S. Da Silva ◽  
Pierre Julien ◽  
Jean-François Bilodeau ◽  
Olivier Barbier ◽  
Iwona Rudkowska

2018 ◽  
Vol 119 (3) ◽  
pp. 239-249 ◽  
Author(s):  
Alix Warburton ◽  
Olga Vasieva ◽  
Peter Quinn ◽  
James P. Stewart ◽  
John P. Quinn

Abstractn-3 Fatty acids, flavonoids and resveratrol are well publicised for their beneficial effects on human health and wellbeing. Identifying common, underlying biological mechanisms targeted by these functional foods would therefore be informative for the public health sector for advising on nutritional health and disease, food and drug product development and consumer interest. The aim of this study was to explore the potential effects of gene expression changes associated with n-3 fatty acids EPA and DHA, flavonoids and resveratrol on modifying biological systems and disease pathways. To test this, publicly available human microarray data for significant gene expression changes associated with dietary intervention with EPA/DHA, flavonoids and resveratrol was subjected to pathway analysis and significance testing for overlap with signals from genome-wide association studies (GWAS) for common non-communicable diseases and biological functions. There was an enrichment of genes implicated in immune responses and disease pathways which was common to all of the treatment conditions tested. Analysis of biological functions and disease pathways indicated anti-tumorigenic properties for EPA/DHA. In line with this, significance testing of the intersection of genes associated with these functional foods and GWAS hits for common biological functions (ageing and cognition) and non-communicable diseases (breast cancer, CVD, diabesity, neurodegeneration and psychiatric disorders) identified significant overlap between the EPA/DHA and breast cancer gene sets. Dietary intervention with EPA/DHA, flavonoids and resveratrol can target important biological and disease pathways suggesting a potentially important role for these bioactive compounds in the prevention and treatment of dietary-related diseases.


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