Abstract 19144: Fish Oil and Cyclooxygenase Inhibitors: a Novel Strategy to Manage Obesity-linked Dyslipidemia

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Viswanathan Saraswathi ◽  
Curtis Perriotte-Olson ◽  
Robert D Heineman ◽  
Cyrus V Desouza

Introduction: Dyslipidemia is a prevalent condition in obesity and type 2 diabetes. Although fish oil rich in omega-3 fatty acids (ω-3) is a widely used hypolipidemic agent, it is often required at high doses. At high doses, these fatty acids can induce oxidative stress or endothelial activation and therefore, strategies to improve their beneficial effects are needed. We previously reported that fish oil in combination with cyclooxygenase (COX) inhibitors exerts enhanced hypolipidemic and anti-inflammatory effects in low density lipoprotein receptor knock-out mice. Here, we sought to determine the effects of ω-3 fatty acids in combination with naproxen (NX), a COX inhibitor, on dyslipidemia and gene expression in subcutaneous adipose tissue (scAT) in humans. Methods: Obese dyslipidemic patients were randomly assigned to receive one of these interventions (n=8/group) for 12 wk: 1) Standard nutrition counseling (control), 2) ω-3 (2 g twice daily), 3) NX (220 mg twice daily), and 4) ω-3 (2 g twice daily) + NX (220 mg twice daily). Results: The body mass index, HOMA-IR, and plasma total, LDL, and HDL cholesterol levels were not altered significantly in any of the groups. The percent change in plasma triglycerides (TG) from baseline was 75% ( P <0.1) and 68% ( P <0.05) in ω-3 and ω3 + NX-treated subjects, respectively. Notably, 25% of subjects who received ω-3s alone did not show a reduction in TG whereas all the patients that received ω-3 + NX showed a reduction in TG. Realtime PCR analysis of scAT showed that the expression of glucose transporter 4 (GLUT-4), a marker of glucose uptake and a key regulator of glucose homeostasis was significantly reduced in ω-3 compared to control group ( P <0.01). However, combining NX with ω-3 abolished this effect. Moreover, the expression of MCP-1 and VCAM-1, markers of inflammatory response or endothelial activation, was significantly increased in ω-3 but not in ω-3 + NX group. The plasma levels of MCP-1 and E-selectin did not vary significantly in any of the groups. Conclusions: Our data reveal previously unrecognized effects of fish oil in scAT. Our data suggest that combining NX with ω-3 fatty acids will increase their effectiveness in reducing plasma TG and improve the benefits of ω-3 supplements by favorably altering gene expression in scAT.

2018 ◽  
Vol 8 (1) ◽  
pp. 6-6 ◽  
Author(s):  
Parisa Jamor ◽  
Hassan Ahmadvand ◽  
Hesam Ashoory ◽  
Esmaeel Babaeenezhad

Background: Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients. Objectives: In the current study, the impact of alpha-lipoic acid (LA), a natural antioxidant and a cofactor in the enzyme complexes on MPO, catalase (CAT) and glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) level, histopathology of kidney and expression of antioxidant enzymes, superoxide dismutase (SOD), GPx and CAT which are involved in the detoxification of reactive oxygen species (ROS), was evaluated in alloxan-induced diabetic rats. Materials and Methods: In this study, 30 male Rattus norvegicus rats randomly divided into three groups; control (C), non-treated diabetic (NTD), and LA-treated diabetics (LATD) was induced by alloxan monohydrate (100mg/kg; subcutaneous [SC]). Then treatment was performed with alphaLA (100 mg/kg intraperitoneal (i.p) daily to 6 weeks). Blood sample of animals collected to measure levels of MPO, CAT and GPx activity GSH and MDA. Kidney paraffin sections were prepared to estimate histological studies and to measure quantitative gene expression SOD, GPX and CAT in kidney. Results: Induction of diabetes led to a significant increase in MPO and MDA, reduced GSH level and GPx and CAT activities (P < 0.05). However, treatment with alpha-LA led to a significant elevation in GPx, CAT and GSH levels with a reduction in MPO activities and MDA levels (P < 0.05). Furthermore, the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis results showed increased expressions of GPx, CAT and SOD enzyme in the treatment group compared with the diabetic control group. Histopathological lesions such as increased glomerular volume and lymphocyte infiltration were attenuated in the alpha-LA treated group. Conclusions: Our findings indicated that alpha-LA supplementation is effective in preventing complications induced by oxidative stress and atherosclerosis in diabetic rats.


2015 ◽  
Vol 86 (10) ◽  
Author(s):  
Marcin Feldo ◽  
Janusz Kocki ◽  
Jan Feldo ◽  
Sylwia Łukasik ◽  
Jacek Bogucki ◽  
...  

Abstractgene and the genes of LRP group play a key role in the regulation of the body weight and lipid metabolism in mammals.was to define the role of. The study group consisted of 38 subjects, including 27 men and 11 women qualified for endovascular aneurysm repair (EVAR). The subjects with abdominal aortic aneurysm were enrolled in the study group, depending on the body mass index (BMI); in obese patients (BMI > 30). The control group (n = 16) included subjects without lipid disorders. One-step isolation of RNA from lymphocytes and adipose tissue cells was performed using the modified TRI method by Chomc-zynski and Sacchi, and then the gene expression was tested by real-time PCR.. The highest mean relative of the gene expression for. Due to the important role of the


2020 ◽  
Author(s):  
Cecilia Gabriela Meléndez-Salcido ◽  
Katya Vargas-Ortiz ◽  
Oscar Gerardo Silva-Gaona ◽  
María Cristina León-García ◽  
Luz Arcelia Ortega-Hernández ◽  
...  

Abstract Background: It has been proposed that curcumin modulates the gene expression of different signaling pathways, improve the fatty acids metabolism and exerts a potential beneficial effect on cardiometabolic disease, but this has not been thoroughly demonstrated. In the present study, we evaluated the effect of curcumin upon the expression of PPARα, CPT1, MCAD, VLCAD and ACAA2 in heart of mice fed a high-fructose diet (HFD). Methods: Twenty-four mice C57BL/6 were divided into four groups (n=6) and treated for 15 weeks. Control group (C) received standard diet (SD), Curcumin group (C+Cur), Fructose group (F) and Fructose with Curcumin group (F+Cur). The groups were treated with 0.75% w/w curcumin mixed in the SD and 30% w/v fructose in water, respectively. Heart proteins expression were analyzed by Western Blot. Results: Curcumin supplementation increased PPARα and ACAA2 expression and decreased CPT1 and MCAD expression in heart of mice fed a HFD. However, it did not modify the VLCAD expression. Conclusions: Curcumin regulated PPARα, CPT1 and MCAD expression and increased ACAA2 expression; suggesting a therapeutic potential in the prevention of alterations in mitochondrial fatty acids metabolism in heart of mice fed a HFD.


2019 ◽  
Vol 59 (6) ◽  
pp. 2759-2769 ◽  
Author(s):  
Kathrin Weiss-Hersh ◽  
Ada L. Garcia ◽  
Tamás Marosvölgyi ◽  
Mónika Szklenár ◽  
Tamás Decsi ◽  
...  

Abstract Purpose We investigated the effect of dietary fats on the incorporation of saturated (SAFAs) and monounsaturated dietary fatty acids (MUFAs) into plasma phospholipids and the regulation of the expression of lipid-metabolizing enzymes in the liver. Methods Mice were fed different diets containing commonly used dietary fats/oils (coconut fat, margarine, fish oil, sunflower oil, or olive oil) for 4 weeks (n = 6 per diet group). In a second experiment, mice (n = 6 per group) were treated for 7 days with synthetic ligands to activate specific nuclear hormone receptors (NHRs) and the hepatic gene expression of CYP26A1 was investigated. Hepatic gene expression of stearoyl-coenzyme A desaturase 1 (SCD1), elongase 6 (ELOVL6), and CYP26A1 was examined using quantitative real-time PCR (QRT-PCR). Fatty acid composition in mouse plasma phospholipids was analyzed by gas chromatography (GC). Results We found significantly reduced hepatic gene expression of SCD1 and ELOVL6 after the fish oil diet compared with the other diets. This resulted in reduced enzyme-specific fatty acid ratios, e.g., 18:1n9/18:0 for SCD1 and 18:0/16:0 and 18:1n7/16:1n7 for ELOVL6 in plasma phospholipids. Furthermore, CYP26A1 a retinoic acid receptor-specific target was revealed as a new player mediating the suppressive effect of fish oil-supplemented diet on SCD1 and ELOVL6 hepatic gene expression. Conclusion Plasma levels of MUFAs and SAFAs strongly reflect an altered hepatic fatty acid-metabolizing enzyme expression after supplementation with different dietary fats/oils.


2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Laura Menchetti ◽  
Olimpia Barbato ◽  
Monica Sforna ◽  
Daniele Vigo ◽  
Simona Mattioli ◽  
...  

Infections of the genital tract can perturb the fertility in humans and animals. Pathogen recognition and activation of innate immunity onset through the pattern recognition receptor activation, such as Toll-like receptor 4 (TLR4), leading to the production of proinflammatory cytokines and mediators. TLR4 is expressed both on leukocytes and nonimmune cells. Rabbit TLR4 shows great similarity to its human counterpart. Moreover, the TLR4 signalling pathway could be modulated by long-chain polyunsaturated fatty acids (LC-PUFA). The objectives of this study were (i) to determine the expression levels of TLR4 and proinflammatory cytokines in the reproductive hypothalamic-gonadal axis of the male rabbit and (ii) to evaluate if the n-3 PUFA-enriched diets can modify their expression levels in the tissues and LC-PUFA profiles in seminal plasma. Fifteen rabbit bucks (n=5/experimental group) were fed with different diets: commercial standard (group C), rich in extruded linseed (10%, group L), and in fish oil (3%, group FO) for 110 days. TLR4, TNF-α, and IL-1β mRNA were ubiquitously expressed throughout the hypothalamic-gonadal axis. However, TLR4 mRNA expression was lower in the hypothalamus than the epididymis (P<0.01), seminal vesicles (P<0.01), and pituitary gland (P<0.05). Dietary enrichment in PUFA did not modify the gene expression profile nor the histological characteristics of the tissues. Conversely in seminal plasma, rabbits fed with L and FO had lower n-6 (P<0.05), LC-PUFA n-6 (P<0.05), and n-6/n-3 ratio (P<0.05) but higher n-3 (P<0.001) and LC-PUFA n-3 (P<0.01) compared to the control group. Our study builds a map of the gene expression of TRL4 and proinflammatory cytokines in the reproductive hypothalamic-gonadal axis of the male rabbit, fundamental step for understanding the immune defence mechanisms. Diets enriched in LC-PUFA did not affect basal gene expression but modulated sperm fatty acid composition. Finally, rabbit may be an excellent animal model to study the relationship between inflammation and infertility, and the nutritional modulation of immune functions.


2020 ◽  
Vol 9 (3) ◽  
pp. 232
Author(s):  
Januar Hadi Prasetyo ◽  
Agustono Agustono ◽  
Widya Paramitha Lokapirnasari

Omega-3 fatty acids (Alpha-linolenic acid) and omega-6 fatty acids (Linoleic acid) are a group of essential fatty acids. Essential fatty acids are fatty acids that cannot be synthesized by the body so that must be supplied from the diet. One of the sources of essential fatty acids is derived from fish oil. This study aims to determine the effect of Crude Fish Oil (CFO) in the feed to EPA and DHA content in penaeid shrimp meat. The research method used was a completely randomized design. The treatments used are the varying content of Crude Fish Oil (CFO), which are P0 (0%), P1 (2%), P2 (4%), P3 (6%), and P4 (8%). The results of the study showed significant differences (p <0.05) on the content of EPA and DHA in penaeid shrimp meat. The highest content of EPA and DHA found in P4 treatment (8%) and the lowest at P0 treatment (0%). The use of CFO in penaeid shrimp feed need further study related to the growth of shrimps and prawns reproductive cycle to increase the productivity of penaeid shrimp. CFO on feed should be used at a dose of 6%.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11102
Author(s):  
Vanessa Martínez-Rivera ◽  
Christian A. Cárdenas-Monroy ◽  
Oliver Millan-Catalan ◽  
Jessica González-Corona ◽  
N. Sofia Huerta-Pacheco ◽  
...  

Background The post-mortem interval (PMI) is the time elapsed since the dead of an individual until the body is found, which is relevant for forensic purposes. The miRNAs regulate the expression of some genes; and due to their small size, they can better support degradation, which makes them suitable for forensic analysis. In the present work, we evaluated the gene expression of miR-381-3p, miR-23b-3p, and miR-144-3p in skeletal muscle in a murine model at the early PMI. Methods We designed a rat model to evaluate the early PMI under controlled conditions. This model consisted in 25 rats divided into five groups of rats, that correspond to the 0, 3, 6, 12 and 24 hours of PMI. The 0 h-PMI was considered as the control group. Muscle samples were taken from each rat to analyze the expression of miR-381-3p, miR-23b-3p, and miR-144-3p by quantitative RT-PCR. The gene expression of each miRNA was expressed as Fold Change (FC) and compared among groups. To find the targets of these miRNAs and the pathways where they participate, we performed an in-silico analysis. From the gene targets of miR-381-3p identified in the silico analysis, the EPC1 gene was selected for gene expression analysis by quantitative RT-PCR in these samples. Also, to evaluate if miR-381-3p could predict the early PMI, a mixed effects model was calculated using its gene expression. Results An upregulation of miR-381-3p was found at 24 h-PMI compared with the control group of 0 h-PMI and (FC = 1.02 vs. FC = 1.96; p = 0.0079). This was the opposite for miR-23b-3p, which had a down-regulation at 24 h-PMI compared to 0 h-PMI (FC = 1.22 vs. FC = 0.13; p = 0.0079). Moreover, the gene expression of miR-381-3p increased throughout the first 24 h of PMI, contrary to miR-23b-3p. The targets of these two miRNAs, participate in biological pathways related to hypoxia, apoptosis, and RNA metabolism. The gene expression of EPC1 was found downregulated at 3 and 12 h of PMI, whereas it remained unchanged at 6 h and 24 h of PMI. Using a multivariate analysis, it was possible to predict the FC of miR-381-3p of all but 6 h-PMI analyzed PMIs. Discussion The present results suggest that miR-23b-3p and miR-381-3p participate at the early PMI, probably regulating the expression of some genes related to the autolysis process as EPC1 gene. Although the miR-381-3p gene expression is a potential estimator of PMI, further studies will be required to obtain better estimates.


Author(s):  
N. Ponomarenko ◽  
S. Tsehmistrenko ◽  
O. Tsekhmistrenko ◽  
V. Polishchuk ◽  
S. Polishchuk

There were investigated the level of common lipids and the ratio of their individual classes – phospholipids, monoacylglycerols, diacylglycerols and triacylglycerols, free and esterified cholesterol, unesterified fatty acids in the 6–8 weeks old quails pancreas (the period of laying eggs formation) under condition of nitrates influence and feeding of mixed fodder with the addition of amaranth seeds. The body's response to nitrate loading and the feeding of amaranth seeds was evaluated according to biochemical parameters in the pancreas, one of the largest glands in the body. For laboratory experiments there were used quails by Pharaon breed. Quails were divided into three groups of 60 heads in each, fed the standard feed, access to feed and water was free. The birds of the first group served as control, the birds of the second group, in order to model the stress state, water was dispensed with sodium nitrate at a dose of 0.5 g / kg of body weight. Birds of the third group were fed a mixed fodder with seeds of amaranth at the rate of 10 % of the mass of mixed fodder on the background of nitrate loading. Decapitation was performed under etheric anesthesia and the pancreas was taken from a 6-week-old birds (the beginning of the laying eggs period). In the extract of the pancreas, the content of total lipids and their individual classes were were srudied and expressed as a percentage of the total number of lipids. For identification of lipids on a chromatographic plate, the standard preparations of individual lipids from Sigma (USA) were used. The obtained results indicate that nitrate loading leads to a decrease in the common lipids content in the quail pancreas tissues. Thus, their number in the 6-week-old age is reduced by 37.0 % (p<0.05), and in the 8-week-old period – by 22.7 % (p<0.05) compared with the control group. Lipids perform structural and energy functions, as well as determine the important role for the adaptation of the organism to stress factors. Due to the long nitrate influence and due to the unequal functionality of the antioxidant systems of the body, protective mechanisms are violated, which leads to the occurrence of pathological processes. At the same time there are certain changes in the ratio of individual classes of lipids. In particular, the content of unesterified fatty acids (UFA) in 6-week-old poultry decreases by 13.3 % (p<0.05) and 8-week –12.4 % (p<0.05) compared to control. The level of UFA in tissues and serum is related to the energy supply of the bird organism and characterizes the activity of lipolysis processes and their mobilization from fat depots. The decrease in the tissues of the number of UFA indicates their intensive use in energy processes. Feeding of mixed fodder with seeds of amaranth against the background of nitrate influence causes changes in the total content of lipids and the ratio of their individual classes in pancreatic tissue compared with control and 2nd group. Thus the poultry, which was fed with mixed amaranth seeds alongside with nitrate influence, had increasing of total lipids content in comparison with the 2nd group in the 6-week old age in 2,0 times (p<0,05), in the 8-week-old – in 2,2 times (p<0,001) and in comparison with the control group at 8-year-old in 1,5 times (p<0,05). At the same time, the content of mono- and diacylglycerols is reduced by 15.3–20.9 % (p<0.05), while triacylglycerols increases by 45.5 % relative to the control (p<0.05). Feeding amaranth seeds to quail results in an increase in the content of esters of cholesterol in the 8-week-old age by 1.3 times (p<0.05) compared to the second group and, as compared with control, their content increases in the pancreas of 6–8 weeks old birds by 20,9–36.7 % (p<0.05). These patterns indicate that inhibition of lipolysis and accumulation of reserve lipids in pancreatic tissue is inhibited. The increase in the number of cholesterol esters indicates their active use in the bird organism as a result of changes in the processes of esterification and hydrolysis of cholesterol under the influence of biologically active substances of the seeds of amaranth, in particular squalene. It can be assumed that when entering the body, amaranth seed squalene initially leads to an increase in the content of cholesterol in the pancreas, since it is a precursor to the synthesis of cholesterol. Accordingly, the increase of cholesterol content activates the enzyme acyl-CoA-cholesterol-acyltransferase, while the content of cholesterol esters begins to increase. It is worth noting that the steroid core in cholesterol esters is more resistant to oxidation and, possibly, for this reason, the cell is better stored cholesterol in the form of esters. Amaranth bird feeding on the background of nitrate loading prevents the decrease of the total lipids content and contributes to the accumulation of reserve lipids in the pancreas. It can be explained by the content of amaranth polyunsaturated fatty acids, which, along with vitamins and trace elements, regulate lipid metabolism in the bird organism. Thus, nitrate influence leads to a decrease in the total content of lipids in pancreatic tissue of 6–8 weeks-old quails and a decrease in the amount of unesterified fatty acids, which indicates the intensive their using in energy processes. Feeding of poultry with mixed fodder with amaranth seeds during the period of laying eggs formation perion on the background of nitrate influence contributes to increase of total lipids content to the level of control group. Along with this, changes in the ratio of individual classes of lipids have been established, which are manifested by a decrease in the content of mono- and diacylglycerols and an increase in the content of cholesterol esters. Key words: phospholipids, monoacylglycerols, diacylglycerols, triacylglycerols, free cholesterol, cholesterol esters, unesterified fatty acids, pancreas, nitrates, quails, amaranth.


2019 ◽  
Vol 47 (3) ◽  
Author(s):  
Linling LI ◽  
Jie YU ◽  
Honghui YUAN ◽  
Sanxing ZHA ◽  
Kun DENG ◽  
...  

As one of the rare and precious wood species since the ancient times, Gingko is also known as “living fossil”, which is a special plant resource of China. Gingko leaves, containing rich flavonoids, are valued with great medicinal significances. This paper treated Ginkgo seedlings by exogenous Sodium selenite (SS) in two ways: Foliage dressing (FD) and Root application (RA). Then transcriptome sequencing and metabolome test are performed. Results show that external SS has significant influence on the related gene expression level of flavonoids synthesis ways of Gingko, the FD can significantly induce gene expressions as CHS, FLS, FOMT, PAL, MYB1 and MYB2, and RA can significantly induce gene expressions as FOMT, MYB1 and MYB2. Compared with the control group, FA selenium application can help to accumulation of flavonoids, flavonols, flavonoids-C and isoflavones, especially quercetin and kaempferol that had a remarkable increase. This proved that a proper concentration of inorganic SS could promote the synthesis and accumulation of flavonoids in Gingko. qRT-PCR analysis also depicts that leaves treatment of sodium selenite can remarkably enhance the gene expression of CHS, FLS, FOMT and PAL, and RA selenium application can induce the gene expression of FLS and FOMT, but restrain the gene expression of CHS and PAL. Through the ways of FD and RA selenium application, this paper basically studied the regulatory effect of SS on ginkgo flavonoids synthesis and has laid a theoretical basis to improve flavonoids content in Ginkgo leaves through cultivation control means.   *********   In press - Online First. Article has been peer reviewed, accepted for publication and published online without pagination. It will receive pagination when the issue will be ready for publishing as a complete number (Volume 47, Issue 3, 2019). The article is searchable and citable by Digital Object Identifier (DOI). DOI link will become active after the article will be included in the complete issue.   *********


2020 ◽  
Vol 65 (No. 2) ◽  
pp. 51-57
Author(s):  
Hongtao Ren ◽  
Guang-Qin Zhang ◽  
Yong Huang ◽  
Xiao-Chan Gao

The effects of fatty acid composition in artificial feed on the change in the fatty acid composition of carp muscles and the relationship between Δ6-Fad and Elovl5 genes participating in the regulation of fatty acid synthesis were studied. Juveniles were fed three semi-purified diets (D1–D3) for 6 weeks with different lipid sources: D1, fish oil with high highly unsaturated fatty acids (HUFA); D2, corn oil with high linoleic acid (18:2n-6, LA), D3, linseed oil with high α-linolenic acid (18:3n-3, LNA); then, samples were taken to explore the molecular mechanism and the factors which affect the synthesis of carp HUFA. The content of LA and arachidonic acid (20:4n-6, AA) in common carp fed Diet 2 was higher than in carp receiving D3 (P &lt; 0.05), but the contents of eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) were lower than in carp fed D1 and D2 (P &lt; 0.05). The liver transcript abundance of Δ6-Fad and Elovl5 in fish fed D2 and D3 at the end of 6 weeks was generally higher than the abundance in the initial stage and in the fish fed D1 (P &lt; 0.05). The results suggest that the common carp can biosynthesise HUFA, and the type and content of fatty acids in feed affected not only the composition and content of fatty acids in common carp muscles, but also the Δ6-Fad and Elovl5 gene expression involved in the biosynthesis of HUFA. Feeding high levels of n-3 HUFA diet can increase the body content of EPA and DHA in common carp. The results of this research may provide a theoretical basis for choosing an appropriate source of lipid for common carp feeds.  


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