scholarly journals Low amounts of trans 18 : 1 fatty acids elevate plasma triacylglycerols but not cholesterol and alter the cellular defence to oxidative stress in mice

2005 ◽  
Vol 94 (3) ◽  
pp. 346-352 ◽  
Author(s):  
Nadège Cassagno ◽  
Antonio Palos-Pinto ◽  
Pierre Costet ◽  
Dominique Breilh ◽  
Michel Darmon ◽  
...  

Trans fatty acids are found mainly in processed foods. It has been shown that when their intake is high, total cholesterol, LDL-cholesterol and triacylglycerols are elevated, while HDL-cholesterol decreases. To evaluate a possible effect of these compounds, even in low amounts, C57Bl/6J mice were fed for 7 weeks a diet containing 13·6 % energy as partially hydrogenated rapeseed oil-enriched diet (Trans diet). The Trans diet contained 3 % energy as trans 18 : 1 fatty acid (elaidic acid). Control mice were on an isologous diet containing native rapeseed oil (Rapeseed diet) in which trans fatty acids were undetectable. Total, free and HDL-cholesterol as well as reverse cholesterol transport did not change. However, plasma triacylglycerol and VLDL levels increased. Hepatic gene expression in the Trans v. Rapeseed diet were compared using quantitative RT–PCR. The Trans diet produced a 2–3-fold elevation in mRNA of fatty acid synthase and microsomal transfer protein mRNA, explaining (at least in part) the observed increase in triacylglycerols and VLDL. In addition, mice on the Trans diet developed a deficiency in plasma vitamin E accompanied by a higher concentration of F2-isoprostanes, indicative of increased oxidative stress. The 78 kDa glucose-related protein (GRP78) mRNA expression increased 3–4-fold in liver, suggesting that a response against apoptosis was provoked by lipid peroxidation.

Author(s):  
E-Ming Rau ◽  
Inga Marie Aasen ◽  
Helga Ertesvåg

Abstract Thraustochytrids are oleaginous marine eukaryotic microbes currently used to produce the essential omega-3 fatty acid docosahexaenoic acid (DHA, C22:6 n-3). To improve the production of this essential fatty acid by strain engineering, it is important to deeply understand how thraustochytrids synthesize fatty acids. While DHA is synthesized by a dedicated enzyme complex, other fatty acids are probably synthesized by the fatty acid synthase, followed by desaturases and elongases. Which unsaturated fatty acids are produced differs between different thraustochytrid genera and species; for example, Aurantiochytrium sp. T66, but not Aurantiochytrium limacinum SR21, synthesizes palmitoleic acid (C16:1 n-7) and vaccenic acid (C18:1 n-7). How strain T66 can produce these fatty acids has not been known, because BLAST analyses suggest that strain T66 does not encode any Δ9-desaturase-like enzyme. However, it does encode one Δ12-desaturase-like enzyme. In this study, the latter enzyme was expressed in A. limacinum SR21, and both C16:1 n-7 and C18:1 n-7 could be detected in the transgenic cells. Our results show that this desaturase, annotated T66Des9, is a Δ9-desaturase accepting C16:0 as a substrate. Phylogenetic studies indicate that the corresponding gene probably has evolved from a Δ12-desaturase-encoding gene. This possibility has not been reported earlier and is important to consider when one tries to deduce the potential a given organism has for producing unsaturated fatty acids based on its genome sequence alone. Key points • In thraustochytrids, automatic gene annotation does not always explain the fatty acids produced. • T66Des9 is shown to synthesize palmitoleic acid (C16:1 n-7). • T66des9 has probably evolved from Δ12-desaturase-encoding genes.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Claire Newlon ◽  
Matthew Muldoon ◽  
Susan Sereika ◽  
Dora Kuan

Background: Greater consumption of omega-3 fatty acids has been associated with lower cardiovascular disease risk. Randomized controlled trials indicate direct, albeit small, beneficial effects of omega-3 fatty acids on plasma triglycerides and blood pressure, yet few studies have tested their impact on insulin resistance and the clustered risk factors comprising the metabolic syndrome. Hypothesis: Short-term supplementation with marine omega-3 polyunsaturated fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) will improve aggregated cardiometabolic risk (CMR) in healthy middle-aged adults Methods: We conducted a double-blind, placebo-controlled, parallel group clinical trial. Subjects were 30-54 year-old adults free of atherosclerotic disease and diabetes whose intake of EPA and DHA totaled <300 mg/day. Each was randomly assigned to daily fish oil supplements (2g/day containing 1000 mg EPA and 400mg DHA) or matching soybean oil placebo for 18 weeks. Aggregate CMR at baseline and post-intervention was calculated as the standardized sum of standardized distributions of blood pressure, BMI, and fasting serum triglycerides, glucose, and HDL (reverse scored). Missing data due to dropouts (n=17) and outliers (1-6 per variable) were replaced by multivariate imputation. Outcome analyses were conducted with linear regressions of all randomized subjects based on intention-to-treat. Results: Participants were 272 healthy adult (57% (154 out of 272) women; 17% (47 out of 272) minority; mean age 42) Pittsburgh-area residents. At baseline, demographics, health parameters, physical activity and EPA and DHA consumption did not differ significantly between treatment groups. No overall treatment effect was found, whereas gender moderated the effects of treatment on CMR risk (gender, p=.001 and gender*treatment interaction term p=.011). In gender-specific analyses, supplementation lowered CMR risk relative to placebo in men(p=.036, effect size=.629, standard error (SE) =.282) but not women (p=.168, effect size .261, SE=.222). Of the individual CMR variables, only HDL-cholesterol in men revealed a significant improvement (p=.012). In men receiving placebo, HDL-cholesterol fell by 1.1 mg/dl, whereas in those receiving fish oil, HDL rose by 1.7 mg/dl. As has been noted in other samples, compared to women men had greater CMR and lower HDL-cholesterol. Conclusions: Increased intake of n-3 fatty acids over 4 months reduced CMR in healthy, mid-life men but not women. This finding may be due to poorer baseline CMR and HDL characteristic of men, or to gender differences in fatty acid metabolism. Further study of gender differences in cardiometabolic risk and fatty acid metabolism may lead to gender-tailored preventive interventions.


2015 ◽  
Vol 40 (2) ◽  
pp. 79-84 ◽  
Author(s):  
T Bashar ◽  
N Akhter

In acute myocardial infarction (AMI), lack of oxygen delivery to myocardium leads to generation of reactive oxygen species (ROS) which play an important role in the pathogenesis of AMI. Endogenous anti-oxidants protect the myocardial tissues from the deleterious effect of free radical mediate injury. The study evaluates the extent of oxidative stress and antioxidant status against ROS in AMI patients and amelioration of oxidative stress after regular treatment and also assesses the association between oxidative stress and risk factors for atherosclerosis like dyslipidemia and diabetes mellitus (DM).The study was conducted on 72 AMI patients and age and sex matched 18 healthy controls. Patients were assigned to four groups, AMI without dyslipidemia or DM, with dyslipidemia, with DM and with both dyslipidemia and DM. Plasma malondialdehyde (MDA) and GSH content and vitamin E levels were determined on admission into hospital and on the 5th day of treatment. Plasma MDA level increased significantly (p<0.001) and erythrocyte GSH and plasma vitamin E levels were decreased (p<0.001) in all the groups of patients as compared to control. On the 5th day of regular treatment MDA level reduced (p<0.001) and GSH and vitamin E levels increased (p<0.001) in patients. The plasma MDA level was significantly higher (p<0.001) in patients with both dyslipidemia and DM or with only DM in comparison to patients without dyslipidemia and DM. The difference in the GSH level between patients with risk factors and without risk factors was not significant. It may be conclude that an imbalance exists between oxidant and antioxidant molecules in AMI patients which shift towards oxidative side and regular treatment restores this balance. There may be some association between oxidative stress in AMI and risk factors like dyslipidemia and diabetes mellitus.Bangladesh Med Res Counc Bull 2014; 40 (2): 79-84


1966 ◽  
Vol 19 (3) ◽  
pp. 147-157 ◽  
Author(s):  
HABIBA HASSAN ◽  
SAMI A. HASHIM ◽  
THEODORE B. VAN ITALLIE ◽  
WILLIAM H. SEBRELL

Author(s):  
Sushil Kumar ◽  
Sajjan Sihag ◽  
Zile Singh Sihag ◽  
Chandershekhar Santosh Patil ◽  
Surender Singh Dhaka ◽  
...  

Background: Supplementation of fat, especially those having unsaturated fatty acids has been proposed to carry positive effects on the reproductive organ, beside providing dietary energy to the animals. This experiment was designed to examine the effects of dietary ω-3 or ω-6 fatty acid (FA) rich oil supplementation on blood FA, metabolite and hormone concentrations; ovarian follicular growth and corpus luteum (CL) size in Sahiwal breed heifers.Methods: Eighteen heifers of 18.33±1.14 months of age and 194±4.16 kg of mean body weight were randomly assigned to 3 diets and individually fed as per ICAR (2013) diets. The diets include chopped wheat straw, green fodder and concentrate mixture containing either (i) no added PUFA rich oil but palm oil @ 3.5% (PO; n=6); (ii) 3.5% added soybean oil as ω-6 FA source (SO; n=6); or (iii) 3.5% added linseed oil as ω-3 FA source (LO; n=6).Result: SO increased (P less than 0.05) the plasma concentration of ω-6 FA while LO increased (P less than 0.05) the plasma ω-3 FA. Plasma glucose, triglyceride and non-esterified fatty acid (NEFA) concentrations was not affected due to different diets. Plasma total cholesterol and HDL-cholesterol were significantly higher (P less than 0.05) in SO and LO in comparison to PO. However, LDL-cholesterol was at par among all the treatments. Growth Hormone (GH) was not influenced due to different types of oil in heifers’ concentrate mixture. Insulin concentration increased (P less than 0.05) in LO compared to others. IGF-1 was statistically higher (P less than 0.05) in SO and LO as compared to CON, which among themselves also varied significantly. Plasma progesterone concentration at day 12 post estrous was higher (P less than 0.05) in LO. PUFA rich oil supplementation in the concentrate mixture of heifers (SO and LO) increased (P less than 0.05) the size of the ovulatory follicles as well as size of CL. It was inferred that feeding PUFA rich oil to pre-pubertal Sahiwal heifer’s results in advantageous changes in the blood metabolites, plasma hormones and ovarian functions.


2020 ◽  
Author(s):  
Michael Hulse ◽  
Sarah M Johnson ◽  
Sarah Boyle ◽  
Lisa Beatrice Caruso ◽  
Italo Tempera

Latent membrane protein 1 (LMP1) is the major transforming protein of Epstein-Barr virus (EBV) and is critical for EBV-induced B-cell transformation in vitro. Several B-cell malignancies are associated with latent LMP1-positive EBV infection, including Hodgkin’s and diffuse large B-cell lymphomas. We have previously reported that promotion of B cell proliferation by LMP1 coincided with an induction of aerobic glycolysis. To further examine LMP1-induced metabolic reprogramming in B cells, we ectopically expressed LMP1 in an EBV-negative Burkitt’s lymphoma (BL) cell line preceding a targeted metabolic analysis. This analysis revealed that the most significant LMP1-induced metabolic changes were to fatty acids. Significant changes to fatty acid levels were also found in primary B cells following EBV-mediated B-cell growth transformation. Ectopic expression of LMP1 and EBV-mediated B-cell growth transformation induced fatty acid synthase (FASN) and increased lipid droplet formation. FASN is a crucial lipogenic enzyme responsible for de novo biogenesis of fatty acids in transformed cells. Furthermore, inhibition of lipogenesis caused preferential killing of LMP1-expressing B cells and significantly hindered EBV immortalization of primary B-cells. Finally, our investigation also found that USP2a, a ubiquitin-specific protease, is significantly increased in LMP1-positive BL cells and mediates FASN stability. Our findings demonstrate that ectopic expression of LMP1 and EBV-mediated B-cell growth transformation leads to induction of FASN, fatty acids and lipid droplet formation, possibly pointing to a reliance on lipogenesis. Therefore, the use of lipogenesis inhibitors could potentially be used in the treatment of LMP1+ EBV associated malignancies by targeting a LMP1-specific dependency on lipogenesis. Importance Despite many attempts to develop novel therapies, EBV-specific therapies currently remain largely investigational and EBV-associated malignancies are often associated with a worse prognosis. Therefore, there is a clear demand for EBV-specific therapies for both prevention and treatment of viral-associated malignancies. Non-cancerous cells preferentially obtain fatty acids from dietary sources whereas cancer cells will often produce fatty acids themselves by de novo lipogenesis, often becoming dependent on the pathway for cell survival and proliferation. LMP1 and EBV-mediated B-cell growth transformation leads to induction of FASN, a key enzyme responsible for the catalysis of endogenous fatty acids. Preferential killing of LMP1-expressing B cells following inhibition of FASN suggests that targeting LMP-induced lipogenesis could be an effective strategy in treating LMP1-positive EBV-associated malignancies. Importantly, targeting unique metabolic perturbations induced by EBV could be a way to explicitly target EBV-positive malignancies and distinguish their treatment from EBV-negative counterparts.


2020 ◽  
Vol 117 (38) ◽  
pp. 23557-23564
Author(s):  
Alex Ruppe ◽  
Kathryn Mains ◽  
Jerome M. Fox

Cells build fatty acids with biocatalytic assembly lines in which a subset of enzymes often exhibit overlapping activities (e.g., two enzymes catalyze one or more identical reactions). Although the discrete enzymes that make up fatty acid pathways are well characterized, the importance of catalytic overlap between them is poorly understood. We developed a detailed kinetic model of the fatty acid synthase (FAS) ofEscherichia coliand paired that model with a fully reconstituted in vitro system to examine the capabilities afforded by functional redundancy in fatty acid synthesis. The model captures—and helps explain—the effects of experimental perturbations to FAS systems and provides a powerful tool for guiding experimental investigations of fatty acid assembly. Compositional analyses carried out in silico and in vitro indicate that FASs with multiple partially redundant enzymes enable tighter (i.e., more independent and/or broader range) control of distinct biochemical objectives—the total production, unsaturated fraction, and average length of fatty acids—than FASs with only a single multifunctional version of each enzyme (i.e., one enzyme with the catalytic capabilities of two partially redundant enzymes). Maximal production of unsaturated fatty acids, for example, requires a second dehydratase that is not essential for their synthesis. This work provides a kinetic, control-theoretic rationale for the inclusion of partially redundant enzymes in fatty acid pathways and supplies a valuable framework for carrying out detailed studies of FAS kinetics.


2019 ◽  
Vol 71 (1) ◽  
pp. 303-313 ◽  
Author(s):  
C. Esteves ◽  
K.G. Livramento ◽  
L.V. Paiva ◽  
A.P. Peconick ◽  
I.F.F. Garcia ◽  
...  

ABSTRACT The present study aimed to evaluate the occurrence of polymorphisms in Diacylglycerol acyltransferase (DGTA-1 and 2), Fatty acid synthase (FASN), Stearoyl-CoA desaturase (SCD) genes and the Thioesterase domain of FASN (TE-FASN) gene that may be related to the lipid profile. In the experiment, a total of 84 sheep from different genetic groups were used. For the evaluation of the polymorphism of the genes, PCR-Single Strand Conformation Polymorphism (SSCP) technique and subsequent sequencing were used. In DGAT-2 gene, four genotypes were identified with the presence of 6 polymorphisms, with two (c.229T> C; c.255T> C) that resulted into the exchange of phenylalanine by leucine. In FASN gene, two genotypes were identified. In TE-FASN gene, three genotypes and 17 polymorphisms were identified. DGAT-1 and SCD genes did not reveal the occurrence of polymorphism. There was difference in relation to C14: 0, C18: 0 fatty acids and Δ9-desaturase C18 for DGAT-2 gene and of C18: 2ω6t for TE-FASN. There were differences among the genetic groups for C10: 0, C12: 0, C17: 0, C18: 2ω6t, C18: 3ω3, C20: 2, total of ω3, ω3/ω6 and atherogenicity index. There is occurrence of polymorphism of DGAT-2 and TE-FASN genes and these should be further studied in sheep since they revealed influence of the genotypes on the fatty acid profile.


Sign in / Sign up

Export Citation Format

Share Document