Long-chain PUFAs (LCPUFAs) occur in foods primarily in the natural lipid classes, triacylglycerols (TAGs) or phospholipids (PLs). We studied the relative efficacy of the neural omega-3 DHA provided in formula to growing piglets as a dose of (13)C-DHA bound to either TAG or phosphatidylcholine (PC). Piglets were assigned to identical formula-based diets from early life and provided with TAG-(13)C-DHA or PC-(13)C-DHA orally at 16 days. Days later, piglet organs were analyzed for (13)C-DHA and other FA metabolites. PC-(13)C-DHA was 1.9-fold more efficacious for brain gray matter DHA accretion than TAG-(13)C-DHA, and was similarly more efficacious in gray matter synaptosomes, retina, liver, and red blood cells (RBCs). Liver labeling was greatest, implying initial processing in that organ followed by export to other organs, and suggesting that transfer from gut to bloodstream to liver in part drove the difference in relative efficacy for tissue accretion. Apparent retroconversion to 22:5n-3 was more than double for PC-(13)C-DHA and was more prominent in neural tissue than in liver or RBCs. These data directly support greater efficacy for PC as a carrier for LCPUFAs compared with TAG, consistent with previous studies of arachidonic acid and DHA measured in other species.
Abstract Beige adipocytes are induced by cold temperatures or β3-adrenergic receptor (Adrb3) agonists. They create heat through glucose and fatty acid (FA) oxidation, conferring metabolic benefits. The distinct and shared mechanisms by which these treatments induce beiging are unknown. Here, we performed single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) on adipose tissue from mice exposed to cold or an Adrb3 agonist to identify cellular and chromatin accessibility dynamics during beiging. Both stimuli induce chromatin remodeling that influence vascularization and inflammation in adipose. Beige adipocytes from cold-exposed mice have increased accessibility at genes regulating glycolytic processes, whereas Adrb3 activation increases cAMP responses. While both thermogenic stimuli increase accessibility at genes regulating thermogenesis, lipogenesis, and beige adipocyte development, the kinetics and magnitudes of the changes are distinct for the two stimuli. Accessibility changes at lipogenic genes are linked to functional changes in lipid composition of adipose. Both stimuli tend to decrease the proportion of palmitic acids, a saturated FA in adipose. However, Adrb3 activation increases the proportion of monounsaturated FAs, whereas cold increases the proportion of polyunsaturated FAs. These findings reveal common and distinct mechanisms of cold and Adrb3 induced beige adipocyte biogenesis, and identify the unique functional consequences of manipulating these pathways in vivo .
The fatty acid and volatile compound compositions of camellia oil were analyzed in this study. The impacts of the replacement of conventional vegetable oil with camellia oil on the sensory attributes of dried seaweed were also determined. C18:1 (83.59%), followed by C16:0 and C18:2, were the most abundant fatty acids in camellia oil. A total of 11 and 32 volatile compounds were identified in camellia oil and sesame oil, respectively. In the preference test, the camellia oil samples received a higher, although insignificant, liking rating in overall acceptability of appearance. Overall, there were no differences between the sensory attributes of camellia oil and sesame oil. This finding, combined with the unique fatty acid composition, thermal stability, and health benefits of camellia oil indicate that further study into the use of camellia oil in foods is warranted.
COVID-19 symptoms vary from silence to rapid death, the latter mediated by both a cytokine storm and a thrombotic storm. SARS-CoV (2003) induces Cox-2, catalyzing the synthesis, from highly unsaturated fatty acids (HUFA), of eicosanoids and docosanoids that mediate both inflammation and thrombosis. HUFA balance between arachidonic acid (AA) and other HUFA is a likely determinant of net signaling to induce a healthy or runaway physiological response. AA levels are determined by a non-protein coding regulatory polymorphisms that mostly affect the expression of FADS1, located in the FADS gene cluster on chromosome 11. Major and minor haplotypes in Europeans, and a specific functional insertion-deletion (Indel), rs66698963, consistently show major differences in circulating AA (>50%) and in the balance between AA and other HUFA (47–84%) in free living humans; the indel is evolutionarily selective, probably based on diet. The pattern of fatty acid responses is fully consistent with specific genetic modulation of desaturation at the FADS1-mediated 20:3→20:4 step. Well established principles of net tissue HUFA levels indicate that the high linoleic acid and low alpha-linoleic acid in populations drive the net balance of HUFA for any individual. We predict that fast desaturators (insertion allele at rs66698963; major haplotype in Europeans) are predisposed to higher risk and pathological responses to SARS-CoV-2 could be reduced with high dose omega-3 HUFA.
Abstract Background There is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. Objective We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high oleic (HO) peanuts, with or without added DHA, improves cognition when compared to standard RUTF (S-RUTF). Methods A triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF; DHA-HO-RUTF, HO-RUTF and S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global and 4 domain (gross motor, fine motor, language and social) z-scores and a modified Willatts problem solving assessment (PSA) intention score for 3 standardized problems, measured 6 months and immediately after completing RUTF therapy, respectively. Plasma fatty acid content, anthropometry and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF. Results Among the 2565 SAM children enrolled, global MDAT z-score was -0.69 ± 1.19 and - 0.88 ± 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI 0.01 to 0.38). The gross motor and social domains had higher z-scores among children receiving either DHA-HO-RUTF than S-RUTF. The PSA problem 3 scores did not differ by dietary group (Odds ratio 0.92, 95% CI 0.67 to 1.26 for DHA-HO-RUTF). After 4 weeks of treatment, plasma phospholipid EPA and α-linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared to S-RUTF (for all 4 comparisons P values < 0.001), but only plasma DHA was greater in DHA-HO-RUTF than S-RUTF ( P <0.001). Conclusions Treatment of uncomplicated SAM with DHA-HO-RUTF resulted in an improved MDAT score, conferring a cognitive benefit six months after completing diet therapy. This treatment should be explored in operational settings.
Saturated branched chain fatty acids (BCFA) terminating with either an isopropyl or sec-butyl group, are common bioactive food components consumed from beef, fish, and dairy products. Little is known about their endogenous metabolism and the enzymes mediating their interconversion. Our main objective was to test the substrate specificity of the fatty acid elongases (ELOVL1–7) towards elongation of representative BCFA, anteiso-15:0 and iso-18:0. We also assessed competition between BCFA and normal saturated fatty acid (n-SFA). MCF7 human breast cancer cells are used for functional studies. PcDNA3.1 expression vector was used to clone seven open reading frames of ELOVL transcripts (ELOVL1–7). MCF7 cells were transiently transfected with specific ELOVL1–7 transgene vector or empty vector (control). After 24 h incubation, the transfected MCF7 cells were treated with BSA-bound substrates. After additional 24 h incubation, cells were harvested by trypsinization, fatty acid methyl esters prepared and analyzed quantitatively by GC-FID. Fatty acid composition was characterized by gas chromatography (GC) –electron ionization mass spectrometry (EIMS) and EIMS/MS for branched carbon chain. Transient transfection of ELOVL1–7 into MCF7 cells show that ELOVL6 had highest activity towards elongation of anteiso-15:0→anteiso-17:0, followed by ELOVL5 which showed moderate activity. ELOVL3 was found to be most active ELOVL mediating elongation of iso-18:0→iso-20:0. Our competition results show in ELOVL6 cells anteiso-15:0 competes with n-SFA n-16:0, whereas, in ELOVL3 cells iso-18:0 competes with n-18:0. The elongation of anteiso-15:0 and iso-18:0 BCFA is predominantly operated by the ELOVL6 and ELOVL3, respectively that are well known to operate on normal saturated fatty acids, rather than the ELOVL2 and ELOVL5 which operate on lower-melting polyunsaturated fatty acids. The competition between BCFA and n-SFA for ELOVL1–7 mediated elongation may have implications in the skin, sebaceous, and meibomian glands where both normal and BCFA are present at comparable levels. NIH grant R01 AT007003.
This study was performed to discover bifidobacteria isolated from human intestines that optimally convert linoleic acid (LA) to conjugated linoleic acid (CLA) and to optimize the culture conditions of milk fermentation. One hundred and fifty neonatal bifidobacteria were screened for CLA-producing ability, and Bifidobacterium breve LMC 017 was selected as it showed about 90% conversion of free LA in MRS broth. The selected strain showed resistance at 0.5% LA in microaerophillic conditions. When monolinolein (LA 90%) was used as a substrate for CLA production, the conversion rate was lower compared to free LA, but the growth rate was unaffected during the milk fermentation. There was no significant difference in CLA production between aerobic and anaerobic conditions, and little decline in CLA was shown after the maximal CLA level had been reached. CLA production increased by 80% with 24 h of incubation in milk containing additional skim milk (5%), where the proteins may have facilitated the production of CLA by enhancing the interaction of substrate with the bacteria. CLA production did not decline after 9 h of fermentation and an additional 12 weeks of storage with other commercial starters. This demonstrates the possibility of using this strain as a costarter in the production of CLA-enriched yogurt.
This study was performed to characterize natural CLnA isomer production by Bifidobacterium breve LMC520 of human origin in comparison to conjugated linoleic acid (CLA) production. B. breve LMC520 was found to be highly active in terms of CLnA production, of which the major portion was identified as cis-9,trans-11,cis-15 CLnA isomer by GC-MS and NMR analysis. B. breve LMC520 was incubated for 48 h using MRS medium (containing 0.05% l-cysteine·HCl) under different environmental conditions such as atmosphere, pH, and substrate concentration. The high conversion rate of α-linolenic acid (α-LNA) to CLnA (99%) was retained up to 2 mM α-LNA, and the production was proportionally increased nearly 7-fold with 8 mM by the 6 h of incubation under anaerobic conditions at a wide range of pH values (between 5 and 9). When α-LNA was compared with linoleic acid (LA) as a substrate for isomerization by B. breve LMC520, the conversion of α-LNA was higher than that of LA. These results demonstrated that specific CLnA isomer could be produced through active bacterial conversion at an optimized condition. Because many conjugated octadecatrienoic acids in nature are shown to play many positive roles, the noble isomer found in this study has potential as a functional source.
Abstract Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22 bp insertion-deletion within FADS2 , is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro . Here we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the U.S. A much higher I/I genotype frequency was found in Indians (68%) than in the U.S. (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African and some East Asian populations. Basal plasma phospholipid arachidonic acid status was 8% greater in I/I compared to D/D individuals. The biochemical pathway product-precursor difference, arachidonic acid minus linoleic acid, was 31% and 13% greater for I/I and I/D compared to D/D, respectively. Our study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice.
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