The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is the key decisive factor controlling the development of adipocytes. Ligand-mediated activation of PPARγ occurs early during ...adipogenesis and is thought to prime adipose conversion. Although several fatty acids and their derivatives are known to bind to and activate PPARγ, the identity of the ligand(s) responsible for initiating adipocyte differentiation is still a matter of debate. Here we review recent data on pathways involved in ligand production as well as possible endogenous, adipogenic PPARγ agonists.
Direct comparisons between SFAs varying in chain length, specifically palmitic acid (16:0) and stearic acid (18:0), relative to the latter–s metabolic product, oleic acid (18:1), on cardiometabolic ...risk factors are limited.
The aim of this study was to determine the relative comparability of diets enriched in palmitic acid, stearic acid, and oleic acid on inflammation and coagulation markers, T lymphocyte proliferation/ex-vivo cytokine secretion, plasma cardiometabolic risk factors, and fecal bile acid concentrations.
Hypercholesterolemic postmenopausal women (n = 20, mean ± SD age 64 ± 7 y, BMI 26.4 ± 3.4 kg/m2, LDL cholesterol ≥ 2.8 mmol/L) were provided with each of 3 diets 55% energy (%E) carbohydrate, 15%E protein, 30%E fat, with ∼50% fat contributed by palmitic acid, stearic acid, or oleic acid in each diet; 5 wk/diet phase using a randomized crossover design with 2-wk washouts between phases. Outcome measures were assessed at the end of each phase.
Fasting LDL-cholesterol and non–HDL-cholesterol concentrations were lower after the stearic acid and oleic acid diets than the palmitic acid diet (all P < 0.01). Fasting HDL-cholesterol concentrations were lower after the stearic acid diet than the palmitic acid and oleic acid diets (P < 0.01). The stearic acid diet resulted in lower lithocholic acid (P = 0.01) and total secondary bile acid (SBA) concentrations (P = 0.04) than the oleic acid diet. All other outcome measures were similar between diets. Lithocholic acid concentrations were positively correlated with fasting LDL-cholesterol concentrations (r = 0.33; P = 0.011). Total SBA, lithocholic acid, and deoxycholic acid concentrations were negatively correlated with fasting HDL cholesterol (r = −0.51 to −0.44; P < 0.01) concentrations and positively correlated with LDL cholesterol:HDL cholesterol (r = 0.37–0.54; P < 0.01) ratios.
Dietary stearic acid and oleic acid had similar effects on fasting LDL-cholesterol and non–HDL-cholesterol concentrations and more favorable ones than palmitic acid. Unlike oleic acid, the hypocholesterolemic effect of stearic acid may be mediated by inhibition of intestinal hydrophobic SBA synthesis. These findings add to the data suggesting there should be a reassessment of current SFA dietary guidance and Nutrient Facts panel labeling. This trial was registered at clinicaltrials.gov as NCT02145936.
Objective
Little is known about the transfer of essential fatty acids (FAs) across the human blood–brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with ...omega‐3 (n‐3) FAs would change the FA profile of the cerebrospinal fluid (CSF).
Methods
A total of 33 patients (18 receiving the n‐3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double‐blind, placebo‐controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n‐3 FA high in docosahexaenoic acid (DHA) or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation.
Results
At 6 months, the n‐3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n‐3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n‐3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin‐1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers.
Conclusions
Oral supplementation with n‐3 FAs conferred changes in the n‐3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.
Children born preterm are at increased risk of autism spectrum disorder (ASD). n–3 (ω-3) Combined with n–6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing ...early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n–3 fatty acids combined with GLA improve attention-deficit–hyperactivity disorder.
The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors.
This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18–38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors.
Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = − 2.1 points; 95% CI: − 4.1, − 0.2 points; standardized effect size = − 0.71). No other outcome measure reflected a similar magnitude or a significant effect.
This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.
• Recent studies of Arabidopsis have identified several transporters as being important for amino acid uptake. • We used Arabidopsis plants with altered expression of lysine histidine transporter 1 ...(LHT1), amino acid permease 1 (AAP1) and amino acid permease 5 (AAP5) with the aim of disentangling the roles of each transporter in the uptake of different amino acids at naturally occurring concentrations (2-50 μM). • LHT1 mutants displayed reduced uptake rates of l-Gln, l-Ala, l-Glu and l-Asp but not of l-Arg or l-Lys, while AAP5 mutants were affected in the uptake of l-Arg and l-Lys only. Double mutants (lht1aap5) exhibited reduced uptake of all tested amino acids. In the concentration range tested, AAP1 mutants did not display altered uptake rates for any of the studied amino acids. Expression analysis of amino acid transporter genes with important root functions revealed no major differences in the individual mutants other than for genes targeted for mutation. • We conclude that LHT1 and AAP5, but not AAP1, are crucial for amino acid uptake at concentrations typically found in soils. LHT1 and AAP5 displayed complementary affinity spectra, and no redundancy with respect to gene expression was found between the two transporters, suggesting these two transporters have separate roles in amino acid uptake.
Atlantic salmon can synthesize polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (20:5n-3), arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) via activities of very long ...chain fatty acyl elongases (Elovls) and fatty acyl desaturases (Fads), albeit to a limited degree. Understanding molecular mechanisms of PUFA biosynthesis and regulation is a pre-requisite for sustainable use of vegetable oils in aquafeeds as current sources of fish oils are unable to meet increasing demands for omega-3 PUFAs. By generating CRISPR-mediated elovl2 partial knockout (KO), we have shown that elovl2 is crucial for multi-tissue synthesis of 22:6n-3 in vivo and that endogenously synthesized PUFAs are important for transcriptional regulation of lipogenic genes in Atlantic salmon. The elovl2-KOs showed reduced levels of 22:6n-3 and accumulation of 20:5n-3 and docosapentaenoic acid (22:5n-3) in the liver, brain and white muscle, suggesting inhibition of elongation. Additionally, elovl2-KO salmon showed accumulation of 20:4n-6 in brain and white muscle. The impaired synthesis of 22:6n-3 induced hepatic expression of sterol regulatory element binding protein-1 (srebp-1), fatty acid synthase-b, Δ6fad-a, Δ5fad and elovl5. Our study demonstrates key roles of elovl2 at two penultimate steps of PUFA synthesis in vivo and suggests Srebp-1 as a main regulator of endogenous PUFA synthesis in Atlantic salmon.
Acetic acid bacteria (AAB) are widely applied in food, bioengineering and medicine fields. However, the acid stress at low pH conditions limits acetic acid fermentation efficiency and high ...concentration of vinegar production with AAB. Therefore, how to enhance resistance ability of the AAB remains as the major challenge. Amino acids play an important role in cell growth and cell survival under severe environment. However, until now the effects of amino acids on acetic fermentation and acid stress resistance of AAB have not been fully studied.
In the present work the effects of amino acids on metabolism and acid stress resistance of Acetobacter pasteurianus were investigated. Cell growth, culturable cell counts, acetic acid production, acetic acid production rate and specific production rate of acetic acid of A. pasteurianus revealed an increase of 1.04, 5.43, 1.45, 3.30 and 0.79-folds by adding aspartic acid (Asp), and cell growth, culturable cell counts, acetic acid production and acetic acid production rate revealed an increase of 0.51, 0.72, 0.60 and 0.94-folds by adding glutamate (Glu), respectively. For a fully understanding of the biological mechanism, proteomic technology was carried out. The results showed that the strengthening mechanism mainly came from the following four aspects: (1) Enhancing the generation of pentose phosphates and NADPH for the synthesis of nucleic acid, fatty acids and glutathione (GSH) throughout pentose phosphate pathway. And GSH could protect bacteria from low pH, halide, oxidative stress and osmotic stress by maintaining the viability of cells through intracellular redox equilibrium; (2) Reinforcing deamination of amino acids to increase intracellular ammonia concentration to maintain stability of intracellular pH; (3) Enhancing nucleic acid synthesis and reparation of impaired DNA caused by acid stress damage; (4) Promoting unsaturated fatty acids synthesis and lipid transport, which resulted in the improvement of cytomembrane fluidity, stability and integrity.
The present work is the study to show the effectiveness of Asp and Glu on metabolism and acid stress resistance of A. pasteurianus as well as their working mechanism. The research results will be helpful for development of nutrient salts, the optimization and regulation of high concentration of cider vinegar production process.
Fatty acid-binding proteins (FABPs) are a widely expressed group of calycins that play a well established role in solubilizing cellular fatty acids. Recent studies, however, have recast FABPs as ...active participants in vital lipid-signaling pathways. FABP5, like its family members, displays a promiscuous ligand binding profile, capable of interacting with numerous long chain fatty acids of varying degrees of saturation. Certain “activating” fatty acids induce the protein's cytoplasmic to nuclear translocation, stimulating PPARβ/δ transactivation; however, the rules that govern this process remain unknown. Using a range of structural and biochemical techniques, we show that both linoleic and arachidonic acid elicit FABP5's translocation by permitting allosteric communication between the ligand-sensing β2 loop and a tertiary nuclear localization signal within the α-helical cap of the protein. Furthermore, we show that more saturated, nonactivating fatty acids inhibit nuclear localization signal formation by destabilizing this activation loop, thus implicating FABP5 specifically in cis-bonded, polyunsaturated fatty acid signaling.
Intracellular lipid-binding proteins stimulate lipid-induced gene expression.
Fatty acid-binding protein 5 (FABP5) uses a molecular switch that controls nuclear import when complexed with activating fatty acids.
FABP5 is tuned to selectively stimulate peroxisome proliferation-activated receptor β/δ transactivation in response to specific fatty acids based on their structural features.
FABPs provide a second level of regulatory control of nuclear receptor-mediated lipid signaling.
Key message
Genomic editing with CRISPR/Cas9 system can simultaneously modify multiple copies of the
BnaFAD2
gene to develop novel variations in fatty acids profiles in polyploidy rapeseed
.
Fatty ...acid composition affects edible and processing quality of vegetable oil and has been one of the primary targets for genetic modification in oilseed crops including rapeseed (
Brassica napus
). Fatty acid desaturase 2 gene,
FAD2
, is a key player that affects three major fatty acids, namely oleic, linoleic and linolenic acid, in oilseed plants. Previously, we showed that there are four copies of
BnaFAD2
in allotetraploid rapeseed. In this study, we further established spatiotemporal expression pattern of each copy of
BnaFAD2
using published RNA-seq data. Genomic editing technology based on CRISPR/Cas9 system was used to mutate all the copies of
BnaFAD2
to create novel allelic variations in oleic acid and other fatty acid levels. A number of mutants at two targeting sites were identified, and the phenotypic variation in the mutants was systematically evaluated. The oleic acid content in the seed of the mutants increased significantly with the highest exceeding 80% compared with wild type of 66.43%, while linoleic and linolenic acid contents decreased accordingly. Mutations on
BnaFAD2.A5
caused more dramatic changes of fatty acid profile than the mutations on
BnaFAD2.C5
alleles that were identified with gene editing technique for the first time. Moreover, combining different mutated alleles of
BnaFAD2
can even broaden the variation more dramatically. It was found that effects of different mutation types at
BnaFAD2
alleles on oleic levels varied, indicating a possibility to manipulate fatty acid levels by precise mutation at specific region of a gene.
•Qualitative and quantitative analysis of phenolic acids in honey was achieved using HPLC-ECD.•Contents of phenolic acids were decreased after treatment with resins.•Raw honey could be distinguished ...from resins-treated honey based on chromatographic peak areas.•HPLC-ECD allied chemometrics can be applied for quality control of honey.
The adulteration of honey is generally a safety and quality concern for consumers and the industry as a whole. Resin technologies allow harmful substances to enter honey, creating substandard honey, which can enter the market. Thus, it is necessary to identify such illegal products quickly and easily. In this study, HPLC-ECD combined with chemometrics was used to identify raw acacia honey that had been treated with macroporous adsorption resins. The chromatography fingerprints of 46 honey samples were established, and principal component analysis (PCA) and the OPLS-DA identified that differences in some of the chromatographic peaks could be used to distinguish raw from resins-treated raw honeys. 100% correct classification was achieved with test samples, based on the chromatographic peaks identified. These results show that HPLC-ECD, combined with chemometric methods, can identify correctly resins-treated honey and can be applied for the quality control of honey.
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