scholarly journals The differential effects of fatty acids on enterocytic abundance of amyloid-beta

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Susan Galloway ◽  
Ryusuke Takechi ◽  
Michael Nesbit ◽  
Menuka M. Pallebage-Gamarallage ◽  
Virginie Lam ◽  
...  

Abstract Background Consumption of a Western-styled diet enriched in saturated fatty acids (SFA) relative to polyunsaturated fatty acids is positively associated with risk for Alzheimer’s disease. Whilst potential causal mechanism are unclear, there is increasing evidence that chronic ingestion of SFA enriched diets promote increase the plasma levels of lipoprotein-associated amyloid-β (Aβ). However, the effects of dietary mono- and poly-unsaturated fats (MUFA/PUFA) on nascent lipoprotein Aβ abundance have not been previously reported. Methods Wild-type C57BL/6 J mice were maintained on low-fat control chow (LF) or diets enriched in either SFA, MUFA, or PUFA for 9 months. Enterocytic abundance of Aβ was determined with quantitative immunofluorescent microscopy and plasma Aβ was measured by ELISA. Results The chronic ingestion of SFA-enriched diet increased the enterocytic abundance and plasma concentration of Aβ compared to LF control mice. The mice maintained on MUFA or PUFA diet showed comparable enterocytic and plasma Aβ levels to the LF control mice. Conclusions The data indicates that a diet enriched in SFA significantly increases the enterocytic Aβ production and secretion into the circulation, whilst MUFA and PUFA enriched diet do not exert such effects.

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3860-3860
Author(s):  
Douglas Vivona ◽  
Luciene Terezina Lima ◽  
Alice C Rodrigues ◽  
Carolina Tosin Bueno ◽  
Cristiane M Gaitani ◽  
...  

Abstract Background Despite the high efficacy of IM treatment in chronic myeloid leukemia (CML), some patients fail to achieve optimal response. Several studies demonstrated that IM is a substrate of membrane transporters, such as ABCB1 (P-gp, MDR1) and variations in protein expression or activity could affect the pharmacokinetics of IM by reducing or increasing its bioavailability. These alterations could be related with single nucleotide polymorphisms in ABCB1 gene. Previous data confirms that haplotypes containing the mutated alleles for ABCB1 c.1236C>T, c.3435C>T and c.2677G>T showed major structural modifications that result in changes in the conformation of the binding sites of P-gp. These modifications could affect the pharmacokinetics of IM. Aim The aim of this study was to evaluate the influence of the different haplotypes for ABCB1 c.1236C>T, c.3435C>T and c.2677TG>T polymorphisms in IM plasma concentration, P-gp activity and IM response from CML patients treated with standard dose of IM (400 mg/day). Methods Twenty eight patients in chronic phase of CML were selected according to the haplotypes for ABCB1 c.1236C>T, c.3435C>T and c.2677G>T polymorphisms at two health centers in São Paulo, Brazil. Ten patients with ABCB1 1236CC/3435CC/2677GG haplotype comprised the wild-type group and 18 carriers of haplotypes with at least one mutated allele in each genotype for three ABCB1 polymorphisms (10 patients with 1236CT/3435CT/2677GT and 8 with 1236TT/3435TT/2677TT) comprised the mutated group. Patients were matched for IM time of use. All patients were in chronic phase of CML, treated with a standard dose of IM (400 mg/day) for a median time of 63.5±12.6 months and with complete cytogenetic response (CCyR). Major molecular response (MMR) was defined as a reduction of BCR-ABL1 transcripts levels to ≤ 0.1% in the peripheral blood standardized on the International scale. Complete molecular response (CMR) was defined as a reduction ≤0.0032% of BCR-ABL1 transcripts levels. Real-Time PCR was performed to evaluate ABCB1 mRNA expression to control gene GAPDH. P-gp functional activity was determinated by rhodamine123 efflux assay. Analysis of P-gp expression and functional activity were performed by flow cytometry. The determination of plasma concentration of IM was performed by capillary electrophoresis. Results Patients without MMR had lower plasma concentration of IM when compared to those that achieved this response (0.51 µg/mL vs. 1.42 µg/mL, P=0.001) but no association was found between the different haplotypes and IM plasma levels or ABCB1 mRNA/P-gp expression. The median of Rh123 efflux in wild-type and mutated groups was 59.1 (54.8 - 69.5) and 38.3 (27.4 - 47.9) (P<0.05), respectively. Patients who did not achieve MMR showed a higher rate of efflux mediated by P-gp compared to individuals who did not achieve this response (64.7% vs. 45.7%, P =0.001). All patients who did not achieve MMR showed efflux above 60%.There was a strong and positive correlation between ABCB1 mRNA expression and P-gp expression (r=0.747, P=0.001). P-gp activity was positive and moderate correlated with BCR-ABL1 transcripts (r=0.570; P=0.001). Conclusion ABCB1 1236CT/3435CT/2677GT and 1236TT/3435TT/2677TT haplotypes are associated with lower P-gp activity and higher frequency of MMR but not with IM plasma concentration in chronic phase CML patients treated with standard-dose of IM (400 mg/day) Disclosures: No relevant conflicts of interest to declare.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Christopher K. Nyirenda ◽  
Edmond K. Kabagambe ◽  
John R. Koethe ◽  
James N. Kiage ◽  
Benjamin H. Chi ◽  
...  

Objective. To determine whether 24 hr dietary recalls (DR) are a good measure of polyunsaturated fatty acid (PUFA) intake when compared to plasma levels, and whether plasma PUFA is associated with markers of HIV/AIDS progression and cardiovascular disease (CVD) risk.Methods. In a cross-sectional study among 210 antiretroviral therapy-naïve HIV-infected adults from Lusaka, Zambia, we collected data on medical history and dietary intake using 24 hr DR. We measured fatty acids and markers of AIDS progression and CVD risk in fasting plasma collected at baseline.Results. PUFA intakes showed modest correlations with corresponding plasma levels; Spearman correlations were 0.36(p<0.01)for eicosapentaenoic acid and 0.21(p=0.005)for docosahexaenoic acid. While there were no significant associations(p>0.05)between total plasma PUFA and C-reactive protein (CRP) or lipid levels, plasma arachidonic acid was inversely associated with CRP and triglycerides and positively associated with HDL-C, CD4+ T-cell count, and plasma albumin(p<0.05). Plasma saturated fatty acids (SFA) were positively associated with CRP (β= 0.24; 95% CI: 0.08 to 0.40,p=0.003) and triglycerides (β= 0.08; 95% CI: 0.03 to 0.12,p<0.01).Conclusions. Our data suggest that a single DR is inadequate for assessing PUFA intake and that plasma arachidonic acid levels may modulate HIV/AIDS progression and CVD risk.


2016 ◽  
Vol 41 (2) ◽  
pp. 223-223 ◽  
Author(s):  
Kayode A. Balogun

Cardiovascular disease (CVD) is a complicated and multifarious disease, and is the number one cause of mortality worldwide. The pathogenesis of CVD is attributed to the interaction between genetics and environment. There are numerous data that support the cardioprotective properties of omega (n)-3 polyunsaturated fatty acids (PUFA); however, there are also controversial reports. Considering the reported sex and age differences in the pathophysiology of CVD and the metabolism of n-3 PUFA, it is imperative to consider these factors in the cardioprotective effects of n-3 PUFA. The current thesis investigated the effects of n-3 PUFA on the risk factors of CVD, such as dyslipidemia and obesity, with a particular focus on how sex, age, and dose of n-3 PUFA affect lipid and lipoprotein metabolism. The plasma concentrations of lipids and lipoproteins of C57BL/6 mice offspring at weaning and 16 weeks postweaning were chosen as study outcomes to assess the sex, age, and dose-specific effects of n-3 PUFA on markers of dyslipidemia, a well-known risk factor of CVD. A longer exposure to a postnatal diet high in n-3 PUFA increased plasma concentration of low-density lipoprotein (LDL) cholesterol in the offspring in a sex-specific manner; however, the profile of this increase was less atherogenic, as the high n-3 PUFA group had a lower plasma concentration of very small LDL particles in both males and females. There was no effect of high n-3 PUFA diet observed on plasma concentration of high-density lipoprotein cholesterol; however, the high n-3 PUFA group had a higher cholesterol efflux in the male offspring but not in female offspring. Lipidomic analyses revealed that high n-3 PUFA diet led to higher hepatic and plasma concentrations of n-3 PUFA-containing bioactive lipids, such a phosphatidylcholine, lysophosphatidylcholine and free fatty acids, which could positively influence pathways involved in cardioprotection. The effects of dietary n-3 PUFA on obesity at the cellular level was also investigated, using adipocyte hypertrophy as the outcome measure of adipose tissue enlargement. A diet high in n-3 PUFA prevented adipocyte hypertrophy in males, with no effect in females. High n-3 PUFA diet also led to the downregulation of the messenger RNA expression of acyl-CoA:diacylglycerol acyltransferase 2, fatty acid binding protein-4, peroxisome proliferator-activated receptor protein γ, and leptin in males, which are key proteins involved in adipocyte hypertrophy; however, no effect was observed in females. The last study assessed the effects of dose and duration of exposure to dietary n-3 PUFA on docosahexaenoic acid accretion in the brain, and the expression of neurotrophins known to have neuroprotective and cardioprotective benefits. Dietary n-3 PUFA led to an age-dependent increase in the expression of brain-derived neurotrophic factor, tropomyosin receptor kinase, and phosphorylated cyclic AMP response element binding protein. In conclusion, the results from the current thesis demonstrate a sex-, dose-, and age-specific effect of n-3 PUFA on risk factors of CVD, and on novel regulatory pathways by which n-3 PUFA could reduce dyslipidemia and obesity. The results also suggest that n-3 PUFA could be neuroprotective and cardioprotective through a common neurotrophin signalling pathway.


Author(s):  
Tsunehisa Yamamoto ◽  
Jin Endo ◽  
Masaharu Kataoka ◽  
Yoshinori Katsumata ◽  
Kohsuke Shirakawa ◽  
...  

IntroductionLipotoxicity due to obesity is known to lead to cardiac dysfunction. In an earlier study, we found that an increase in the ratio of saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in the membrane of cardiomyocytes causes endoplasmic reticulum (ER) stress. Such stress is hypothesized to be involved in development of SFA-related cardiomyopathy. Another factor affecting the membrane SFA/MUFA ratio is suppression by SFA of SIRT1-mediated stearoyl-CoA desaturase-1 (SCD1), which is involved in converting SFA to MUFA. Therefore, we evaluated whether increasing dietary intake of MUFA can improve the membrane SFA/MUFA ratio.Material and methodsWild-type mice (n = 30) and cardiomyocyte-specific SIRT1 knockout mice (n = 30) were randomly divided into 3 groups and assigned to 16 weeks of a standard mouse diet, 16 weeks of an SFA-rich high-lard diet (HLD), or 8 weeks of a HLD followed by 8 weeks of a MUFA-rich high olive oil diet (HOD switch).ResultsCompared with the control group, the wild-type mice on the HOD diet showed normalized SIRT1-mediated SCD1 signaling, increased membrane SFA/MUFA ratio, decreased ER stress, and improved cardiomyopathy variables. The HLD-fed SIRT1 knockout mice showed greater changes in the SFA/MUFA ratio, ER stress, and cardiomyopathy variables than the wild-type mice. Switching from HLD to HOD ameliorated these phenotypes, although it did not restore the reduced expression of SCD1.ConclusionsThe MUFA-rich diet was found to have a therapeutic effect on SFA-induced cardiomyopathy with diastolic dysfunction by directly rebalancing membrane fatty acid oversaturation and indirectly through the de-inhibition of SIRT1/SCD1 signaling.


2013 ◽  
pp. 145-152 ◽  
Author(s):  
I. KRÁLOVÁ LESNÁ ◽  
P. SUCHÁNEK ◽  
E. BRABCOVÁ ◽  
J. KOVÁŘ ◽  
H. MALÍNSKÁ ◽  
...  

Replacing SAFAs (saturated fatty acids) for vegetable PUFAs (polyunsaturated fatty acids) has a well documented positive effect on the lipoprotein pattern while the direct effect of dietary fatty acids composition on systemic inflammation remains to be proven. In well controlled randomised cross-over study with 15 overweight/obese postmenopausal women, the effect of dietary switch on systemic inflammation was investigated. A two 3 weeks dietary period either with predominant animal fat (SAFA, 29 caloric % SAFA) or vegetable fat (PUFA 25 % caloric % PUFA) were interrupted by wash-out period. The expected increasing effect on SAFA diet to LDL-C (low density cholesterol) and opposite effect of PUFA diet was documented following changes in fatty acid spectrum in VLDL (very low density cholesterol) particles. The switch from SAFA diet to PUFA diet produced a significant change of CRP (C-reactive protein) concentration (p<0.01) whereas similar trend of IL-18 did not reach statistical significance. In this study, previous in vitro results of different SAFA and PUFA proinflammatory effects with well documented molecular mechanisms were first proven in a clinical study. It could be stated that the substantial change of dietary fatty acid composition might influence proinflammatory effect in addition to traditional cardiovascular risk factors.


Genetics ◽  
2021 ◽  
Author(s):  
Ranjan Devkota ◽  
Delaney Kaper ◽  
Rakesh Bodhicharla ◽  
Marcus Henricsson ◽  
Jan Borén ◽  
...  

Abstract The composition and biophysical properties of cellular membranes must be tightly regulated to maintain the proper functions of myriad processes within cells. To better understand the importance of membrane homeostasis, we assembled a panel of five C. elegans strains that show a wide span of membrane composition and properties, ranging from excessively rich in saturated fatty acids (SFAs) and rigid to excessively rich in polyunsaturated fatty acids (PUFAs) and fluid. The genotypes of the five strain are, from most rigid to most fluid: paqr-1(tm3262);paqr-2(tm3410), paqr-2(tm3410), N2 (wild-type), mdt-15(et14);nhr-49(et8), and mdt-15(et14);nhr-49(et8);acs-13(et54). We confirmed the excess SFA/rigidity-to-excess PUFA/fluid gradient using the methods of fluorescence recovery after photobleaching (FRAP) and lipidomics analysis. The five strains were then studied for a variety of cellular and physiological traits and found to exhibit defects in: permeability, lipid peroxidation, growth at different temperatures, tolerance to SFA-rich diets, lifespan, brood size, vitellogenin trafficking, oogenesis and autophagy during starvation. The excessively rigid strains often exhibited defects in opposite directions compared to the excessively fluid strains. We conclude that deviation from wild-type membrane homeostasis is pleiotropically deleterious for numerous cellular/physiological traits. The strains introduced here should prove useful to further study the cellular and physiological consequences of impaired membrane homeostasis.


2006 ◽  
Vol 395 (1) ◽  
pp. 173-181 ◽  
Author(s):  
Pawel Kaliszewski ◽  
Thierry Ferreira ◽  
Beata Gajewska ◽  
Anna Szkopinska ◽  
Thierry Berges ◽  
...  

The Rsp5 ubiquitin ligase plays a role in many cellular processes including the biosynthesis of unsaturated fatty acids. The PIS1 (phosphatidylinositol synthase gene) encoding the enzyme Pis1p which catalyses the synthesis of phosphatidylinositol from CDP-diacyglycerol and inositol, was isolated in a screen for multicopy suppressors of the rsp5 temperature sensitivity phenotype. Suppression was allele non-specific. Interestingly, expression of PIS1 was 2-fold higher in the rsp5 mutant than in wild-type yeast, whereas the introduction of PIS1 in a multicopy plasmid increased the level of Pis1p 6-fold in both backgrounds. We demonstrate concomitantly that the expression of INO1 (inositol phosphate synthase gene) was also elevated approx. 2-fold in the rsp5 mutant as compared with the wild-type, and that inositol added to the medium improved growth of rsp5 mutants at a restrictive temperature. These results suggest that enhanced phosphatidylinositol synthesis may account for PIS1 suppression of rsp5 defects. Analysis of lipid extracts revealed the accumulation of saturated fatty acids in the rsp5 mutant, as a consequence of the prevention of unsaturated fatty acid synthesis. Overexpression of PIS1 did not correct the cellular fatty acid content; however, saturated fatty acids (C16:0) accumulated preferentially in phosphatidylinositol, and (wild-type)-like fatty acid composition in phosphatidylethanolamine was restored.


1985 ◽  
Vol 31 (4) ◽  
pp. 346-351 ◽  
Author(s):  
Panchanon Chattopadhyay ◽  
Santu Kumar Banerjee ◽  
Kalyani Sen ◽  
Parul Chakrabarti

The wild-type Aspergillus niger (V35) does not require fatty acids for growth. Four unsaturated fatty acid auxotrophs designated as UFA1, UFA2, UFA3, and UFA4 have been produced from this organism by treating the conidia of the wild-type strain with a mutagen, N-methyl-N′-nitro-N-nitrosoguanidine, followed by isolation on media containing monounsaturated fatty acids and the nonionic detergent, Brij 58. Optimal growth of the mutants comparable with that of the wild type was achieved with medium supplemented with C16 or C18 unsaturated fatty acids containing at least one cis double bond at the Δ9 position. Some other fatty acids (18:1 Δ11cis and 16:1 Δ9trans) support growth to some extent. The mutants do not grow at all in the presence of saturated fatty acids. Fatty acid analyses of the mutant, UFA2, grown in the presence of different fatty acid supplements reveal that it may be defective in a desaturase system. Experiments with unlabeled and [1-14C]palmitoyl-CoA have shown that the microsomes of the mutant (UFA2) contain a partially defective Δ9-desaturase system.


Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 70-75 ◽  
Author(s):  
Mustafa Ulubay ◽  
Mustafa Ozturk ◽  
Ozlem Ozturk ◽  
Ugur Keskin ◽  
Ulas Fidan ◽  
...  

AbstractWe evaluated the free fatty acids differences in plasma between hyperemesis gravidarum(HG) and healthy pregnant in first trimester pregnancy.ObjectiveWe aimed to compare the plasma levels of DHA, AA and EPA, between HG patients and healthy pregnant womenDesignFifty-two pregnants were involved in the study. Twenty-six pregnants of them were HG as study group, and twenty-six pregnants were enrolled as healthy pregnant women at the similar gestational age. The saturated fatty acids C14, C15, C16, C18, C20, C22, and C24; the omega-3 fatty acids eicosapentaenoic acid, (EPA) and docosahexaenoic acid, (DHA); the omega-6 fatty acids linoleic acid, arachidonic acid (AA), and homo-gamma-linolenic acid; and the omega-9 fatty acids oleic acid, erucic acid, and nervonic acid were analysed by gas chromatography.ResultsStatistically differences was not seen between the groups with maternal age, gestational age, or plasma levels of EPA, DHA, and AA. Statistically significant difference was seen between the groups with plasma levels of C20 and C22(p<0.05). C20 was declined but C22 was rised in the HG patients.ConclusionEPA, DHA, or AA, which related to placental and fetal neural development are not changing from Hyperemesis gravidarum.


2020 ◽  
Vol 61 (9) ◽  
pp. 1537-1547 ◽  
Author(s):  
Motoki Tanaka ◽  
Toshiki Ishikawa ◽  
So Tamura ◽  
Yujiro Saito ◽  
Maki Kawai-Yamada ◽  
...  

Abstract Although cyanobacteria do not possess wax ester synthase/acyl-CoA:diacylglycerol acyltransferase (WS/DGAT), the bacterial enzyme for triacylglycerol (TAG) production, there have been several studies reporting the accumulation of TAG-like compounds in cyanobacteria. In this study, we aimed to evaluate TAG productivity of the ΔrecJ::atfA strain of Synechocystis sp. PCC 6803 generated by inserting atfA encoding WS/DGAT from Acinetobacter baylyi ADP1 into recJ (sll1354), together with the wild type (WT) and the gene-disrupted strain of slr2103 having homology with eukaryotic DGAT2 gene family (Δ2103). Thin-layer chromatography (TLC) of neutral lipids or isolation of the neutral lipid-enriched fraction followed by gas chromatography or liquid chromatography–tandem mass spectrometry was employed for analyses. The ΔrecJ::atfA strain accumulated 0.508 nmol ml−1OD730−1 of TAG after a week of incubation at 100 μmol photons m−2 s−1. The saturated fatty acids C16:0 and C18:0 accounted for about 50% and 20% of the TAG fatty acids, respectively, suggesting that de novo-synthesized fatty acids were preferentially incorporated into TAG molecules. When the neutral lipid profile of the lipid extracts was examined by TLC, a spot located in a slightly lower position compared with the TAG standard was detected in WT but not in the Δ2103 strain. TAG accumulation levels of both strains was only 0.01–0.03 nmol ml−1OD730−1, but the fatty acid composition was substantially different from that of the background. These results suggest that trace amounts of TAG can be produced in Synechocystis cells by enzymes other than Slr2103, and major constituents of the TAG-like spot are unknown lipid species produced by Slr2103.


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