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The American Journal of Clinical... May 2024Extracellular vesicles (EVs) are proposed to play a role in the development of cardiovascular diseases (CVDs) and are considered emerging markers of CVDs. n-3 PUFAs are... (Randomized Controlled Trial)
Randomized Controlled Trial
Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles: a randomized, controlled crossover trial.
BACKGROUND
Extracellular vesicles (EVs) are proposed to play a role in the development of cardiovascular diseases (CVDs) and are considered emerging markers of CVDs. n-3 PUFAs are abundant in oily fish and fish oil and are reported to reduce CVD risk, but there has been little research to date examining the effects of n-3 PUFAs on the generation and function of EVs.
OBJECTIVES
We aimed to investigate the effects of fish oil supplementation on the number, generation, and function of EVs in subjects with moderate risk of CVDs.
METHODS
A total of 40 participants with moderate risk of CVDs were supplemented with capsules containing either fish oil (1.9 g/d n-3 PUFAs) or control oil (high-oleic safflower oil) for 12 wk in a randomized, double-blind, placebo-controlled crossover intervention study. The effects of fish oil supplementation on conventional CVD and thrombogenic risk markers were measured, along with the number and fatty acid composition of circulating and platelet-derived EVs (PDEVs). PDEV proteome profiles were evaluated, and their impact on coagulation was assessed using assays including fibrin clot formation, thrombin generation, fibrinolysis, and ex vivo thrombus formation.
RESULTS
n-3 PUFAs decreased the numbers of circulating EVs by 27%, doubled their n-3 PUFA content, and reduced their capacity to support thrombin generation by >20% in subjects at moderate risk of CVDs. EVs derived from n-3 PUFA-enriched platelets in vitro also resulted in lower thrombin generation, but did not alter thrombus formation in a whole blood ex vivo assay.
CONCLUSIONS
Dietary n-3 PUFAs alter the number, composition, and function of EVs, reducing their coagulatory activity. This study provides clear evidence that EVs support thrombin generation and that this EV-dependent thrombin generation is reduced by n-3 PUFAs, which has implications for prevention and treatment of thrombosis.
CLINICAL TRIAL REGISTRY
This trial was registered at clinicaltrials.gov as NCT03203512.
Topics: Humans; Extracellular Vesicles; Fatty Acids, Omega-3; Male; Female; Cross-Over Studies; Middle Aged; Double-Blind Method; Blood Coagulation; Blood Platelets; Dietary Supplements; Cardiovascular Diseases; Adult; Fish Oils; Aged; Fatty Acids
PubMed: 38484976
DOI: 10.1016/j.ajcnut.2024.03.008 -
Plants (Basel, Switzerland) Feb 2024Seed storage underpins global agriculture and the seed trade and revealing the mechanisms of seed aging is essential for enhancing seed longevity management. Safflower...
Seed storage underpins global agriculture and the seed trade and revealing the mechanisms of seed aging is essential for enhancing seed longevity management. Safflower is a multipurpose oil crop, rich in unsaturated fatty acids that are at high risk of peroxidation as a contributory factor to seed aging. However, the molecular mechanisms responsible for safflower seed viability loss are not yet elucidated. We used controlled deterioration (CDT) conditions of 60% relative humidity and 50 °C to reduce germination in freshly harvested safflower seeds and analyzed aged seeds using biochemical and molecular techniques. While seed malondialdehyde (MDA) and fatty acid content increased significantly during CDT, catalase activity and soluble sugar content decreased. KEGG analysis of gene function and qPCR validation indicated that aging severely impaired several key functional and biosynthetic pathways including glycolysis, fatty acid metabolism, antioxidant activity, and DNA replication and repair. Furthermore, exogenous sucrose and diethyl aminoethyl hexanoate (DA-6) treatment partially promoted germination in aged seeds, further demonstrating the vital role of impaired sugar and fatty acid metabolism during the aging and recovery processes. We concluded that energy metabolism and genetic integrity are impaired during aging, which contributes to the loss of seed vigor. Such energy metabolic pathways as glycolysis, fatty acid degradation, and the tricarboxylic acid cycle (TCA) are impaired, especially fatty acids produced by the hydrolysis of triacylglycerols during aging, as they are not efficiently converted to sucrose via the glyoxylate cycle to provide energy supply for safflower seed germination and seedling growth. At the same time, the reduced capacity for nucleotide synthesis capacity and the deterioration of DNA repair ability further aggravate the damage to DNA, reducing seed vitality.
PubMed: 38475505
DOI: 10.3390/plants13050659 -
Nutrients Mar 2024Altered intestinal health is also associated with the incidence and severity of many chronic inflammatory conditions, which could be attenuated via dietary -3 PUFA...
Effect of Lifelong Exposure to Dietary Plant and Marine Sources of -3 Polyunsaturated Fatty Acids on Morphologic and Gene Expression Biomarkers of Intestinal Health in Early Life.
Altered intestinal health is also associated with the incidence and severity of many chronic inflammatory conditions, which could be attenuated via dietary -3 PUFA interventions. However, little is known about the effect of lifelong exposure to -3 PUFA from plant and marine sources (beginning in utero via the maternal diet) on early life biomarkers of intestinal health. Harems of C57Bl/6 mice were randomly assigned to one of three isocaloric AIN-93G modified diets differing in their fat sources consisting of the following: (i) 10% safflower oil (SO, enriched in -6 PUFA), (ii) 3% flaxseed oil + 7% safflower oil (FX, plant-based -3 PUFA-enriched diet), or (iii) 3% menhaden fish oil + 7% safflower oil (MO, marine-based -3 PUFA-enriched diet). Mothers remained on these diets throughout pregnancy and offspring (n = 14/diet) continued on the same parental diet until termination at 3 weeks of age. In ileum, villi:crypt length ratios were increased in both the FX and MO dietary groups compared to SO ( < 0.05). Ileum mRNA expression of critical intestinal health biomarkers was increased by both -3 PUFA-enriched diets including and compared to SO ( < 0.05), whereas only the FX diet increased mRNA expression of and ( < 0.05) and only the MO diet increased mRNA expression of ( < 0.05). In the proximal colon, both the FX and MO diets increased crypt lengths compared to SO ( < 0.05), whereas only the MO diet increased goblet cell numbers compared to SO ( < 0.05). Further, the MO diet increased proximal colon mRNA expression of and ( < 0.05) and both MO and FX increased mRNA expression of compared to SO ( < 0.05). Collectively, these results demonstrate that lifelong exposure to dietary -3 PUFA, beginning in utero, from both plant and marine sources, can support intestinal health development in early life. The differential effects between plant and marine sources warrants further investigation for optimizing health.
Topics: Mice; Animals; Pregnancy; Female; Fatty Acids, Omega-3; Safflower Oil; Fish Oils; Diet; Mice, Inbred C57BL; Biomarkers; Gene Expression; RNA, Messenger; Fatty Acids
PubMed: 38474847
DOI: 10.3390/nu16050719 -
Circulation Mar 2024
Topics: Humans; Linoleic Acid; Safflower Oil; Barth Syndrome; Diet; Dietary Supplements
PubMed: 38437482
DOI: 10.1161/CIRCULATIONAHA.123.065414 -
Tropical Animal Health and Production Feb 2024The aim of the current study was to determine the effects of dietary supplementation of safflower seed (SS) on the growth performance and hematological parameters of...
The aim of the current study was to determine the effects of dietary supplementation of safflower seed (SS) on the growth performance and hematological parameters of broiler birds along with the physicochemical, textural and sensory attributes of chicken meat. A total of 200 male chickens (7-days-old) were distributed into 5 groups (40 chickens in each) with 5 replicates of 8 chicks in a 42-day experiment. Each group was allocated to one of 5 dietary treatments, i.e., 0, 2.5, 5, 7.5, and 10% SS. The experimental diets were formulated for starter (7 to 21 days) and finisher (22 to 42 days) phases. Inclusion of SS in the diet improved growth performances in treatment groups between 7 and 42 days. The highest and lowest body weights were observed at the 5% SS and 0% SS levels, respectively. The physicochemical attributes of breast and thigh meat were found (P > 0.05) except for crude fat. The crude fat was significantly (P < 0.05) increased with increasing levels of SS in the diet. The inclusion of SS in the diet did not negatively impact the textural properties, i.e., hardness, cohesiveness, springiness, gumminess, chewiness, and shear force of breast and thigh meat. There was no significant difference in the sensory parameters of cooked chicken meat with increasing levels of SS in the diet. The results demonstrated a significant (P < 0.01) improvement in hematological parameters in the blood samples of broiler chickens fed diet supplemented with various levels of SS for five weeks. These findings suggest that, SS may be used as an oil seed for broiler chicken feed.
Topics: Animals; Male; Carthamus tinctorius; Chickens; Dietary Supplements; Meat; Seeds
PubMed: 38411734
DOI: 10.1007/s11250-024-03927-x -
Environmental Research Jun 2024Dioxin-like pollutants (DLPs), such as polychlorinated biphenyl 126 (PCB 126), are synthetic chemicals classified as persistent organic pollutants. They accumulate in...
Dioxin-like pollutants (DLPs), such as polychlorinated biphenyl 126 (PCB 126), are synthetic chemicals classified as persistent organic pollutants. They accumulate in adipose tissue and have been linked to cardiometabolic disorders, including fatty liver disease. The toxicity of these compounds is associated with activation of the aryl hydrocarbon receptor (Ahr), leading to the induction of phase I metabolizing enzyme cytochrome P4501a1 (Cyp1a1) and the subsequent production of reactive oxygen species (ROS). Recent research has shown that DLPs can also induce the xenobiotic detoxification enzyme flavin-containing monooxygenase 3 (FMO3), which plays a role in metabolic homeostasis. We hypothesized whether genetic deletion of Fmo3 could protect mice, particularly in the liver, where Fmo3 is most inducible, against PCB 126 toxicity. To test this hypothesis, male C57BL/6 wild-type (WT) mice and Fmo3 knockout (Fmo3 KO) mice were exposed to PCB 126 or vehicle (safflower oil) during a 12-week study, at weeks 2 and 4. Various analyses were performed, including hepatic histology, RNA-sequencing, and quantitation of PCB 126 and F2-isoprostane concentrations. The results showed that PCB 126 exposure caused macro and microvesicular fat deposition in WT mice, but this macrovesicular fatty change was absent in Fmo3 KO mice. Moreover, at the pathway level, the hepatic oxidative stress response was significantly different between the two genotypes, with the induction of specific genes observed only in WT mice. Notably, the most abundant F2-isoprostane, 8-iso-15-keto PGE2, increased in WT mice in response to PCB 126 exposure. The study's findings also demonstrated that hepatic tissue concentrations of PCB 126 were higher in WT mice compared to Fmo3 KO mice. In summary, the absence of FMO3 in mice led to a distinctive response to dioxin-like pollutant exposure in the liver, likely due to alterations in lipid metabolism and storage, underscoring the complex interplay of genetic factors in the response to environmental toxins.
Topics: Animals; Oxygenases; Polychlorinated Biphenyls; Oxidative Stress; Mice; Mice, Inbred C57BL; Male; Mice, Knockout; Liver; Environmental Pollutants
PubMed: 38373550
DOI: 10.1016/j.envres.2024.118492 -
ACS Omega Feb 2024By dry crystallization, concentrations of unsaturated fatty acids and bioactive compounds can be increased in olein and super-olein fractions in vegetable oils. Among...
Fatty Acid Composition, Phenolic Compounds, Phytosterols, and Lipid Oxidation of Single- and Double-Fractionated Olein of Safflower Oil Produced by Low-Temperature Crystallization.
By dry crystallization, concentrations of unsaturated fatty acids and bioactive compounds can be increased in olein and super-olein fractions in vegetable oils. Among all sources of vegetable oils, safflower oil (SO) possesses the maximum linoleic acid content. To boost the industrial applications of SO, two variants were produced by single- and two-stage crystallization. This study aimed to determine the fatty acid compositions, phenolic compounds, phytosterols, and oxidative stability of fractionated olein (OF) and double-fractionated olein (DFO) produced by dry crystallization. For this, SO was cooled to -45 °C and filtered, the filtrate was denoted as single-fractionated olein (OF), and 40% of this section was taken for analytical purposes, while the remaining 60% was again cooled to -70 °C and filtered, and the filtrate was denoted as double-fractionated olein (DFO). Unfractionated safflower (SO) was used as a control, filled in amber glass bottles, and stored at 20-25 °C for 90 days. Fatty acid compositions and phytosterols were determined by gas chromatography-mass spectrometry (GC-MS). Phenolic compounds and induction periods were determined by high-performance liquid chromatography (HPLC) and Rancimat. GC-MS analysis revealed that the C18:2 contents of SO, OF, and DFO were 77.63 ± 0.82, 81.57 ± 0.44, and 89.26 ± 0.48 mg/100 g ( < 0.05), respectively. The C18:1 contents of SO, OF, and DFO were 6.38 ± 0.19, 7.36 ± 0.24, and 9.74 ± 0.32 mg/100 g ( < 0.05), respectively. HPLC analysis showed that phenolic compounds were concentrated in the low-melting-point fractions. In DFO, concentrations of tyrosol, rutin, vanillin, ferulic acid, and sinapic acid were 57.36 ± 0.12, 129.45 ± 0.38, 165.11 ± 0.55, 183.61 ± 0.15, 65.94 ± 0.11, and 221.75 ± 0.29 mg/100 g, respectively. In SO, concentrations of tyrosol, rutin, vanillin, ferulic acid, and sinapic acid were 24.79 ± 0.08, 78.93 ± 0.25, 115.67 ± 0.41, 34.89 ± 0.51, and 137.26 ± 0.08 mg/100 g, respectively. In OF, concentrations of tyrosol, rutin, vanillin, ferulic acid, and sinapic acid were 35.96 ± 0.20, 98.69 ± 0.64, 149.14 ± 0.13, 57.53 ± 0.74, and 188.28 ± 0.82 mg/100 g, respectively. The highest concentrations of brassicasterol, campesterol, stigmasterol, β-sitosterol, avenasterol, stigmastenol, and avenasterol were noted in DFO followed by OF and SO. The total antioxidant capacities of SO, OF, and DFO were 54.78 ± 0.12, 71.36 ± 0.58, and 86.44 ± 0.28%, respectively. After the end of the storage time, the peroxide values (POVs) of SO, OF, and DFO stored for 3 months were 0.68, 0.85, and 1.16 mequiv O/kg, respectively, with no difference in the free fatty acid content.
PubMed: 38371827
DOI: 10.1021/acsomega.3c08099 -
Biomedical Research (Tokyo, Japan) 2024Fish oil (FO) is rich in the n-3 polyunsaturated fatty acids. It has been demonstrated that FO intake possesses lipid-lowering properties. Conversely, a high-cholesterol...
Fish oil (FO) is rich in the n-3 polyunsaturated fatty acids. It has been demonstrated that FO intake possesses lipid-lowering properties. Conversely, a high-cholesterol (CH) diet promotes lipid accumulation in the liver and induces fatty liver. This study investigated the effects of FO feeding on hepatic lipid accumulation induced by high-cholesterol feeding in KK mice. All experimental diets had a fat energy ratio of 25%, the SO group had all fat sources as safflower oil (SO), the 12.5 FO group had half of the SO replaced with FO, and the 25 FO group had all of the SO replaced with FO, each with or without 2 weight % (wt%) cholesterol (SO/CH, 12.5 FO/CH, and 25 FO/CH groups, respectively), for 8 weeks. The hepatic triglyceride and total cholesterol levels were significantly lower in the 25 FO/CH group than in the SO/CH group. The hepatic mRNAs of fatty acid synthesis-related genes were downregulated by the FO feeding groups. In view of importance to establish the benefit of FO for preventing severe NAFLD, our results suggest that FO intake prevents excessive hepatic fat accumulation induced by a high-cholesterol diet in obese KK mice through the inhibition of fatty acid synthesis.
Topics: Mice; Animals; Fish Oils; Lipid Metabolism; Liver; Cholesterol; Fatty Acids; Obesity
PubMed: 38325844
DOI: 10.2220/biomedres.45.33 -
The Journal of Nutrition Mar 2024Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural...
BACKGROUND
Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, is required to remodel nascent cardiolipin (CL) to its tetralinoleoyl cardiolipin (LCL, CL with 4 LA side chains) form, which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic LCL concentrations and improve mitochondrial respiration in the liver compared with a diet rich in monounsaturated and saturated fatty acids.
OBJECTIVES
The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), compared with the one fortified with lard (LD), to increase concentrations of LCL and improve mitochondrial respiration in the livers of mice.
METHODS
Twenty-four (9-wk-old) C57 BL/J6 male mice were fed either the SO or LD diets for ∼100 d, whereas food intake and body weight, fasting glucose, and glucose tolerance tests were performed to determine any changes in glycemic control.
RESULTS
Livers from mice fed SO diet had higher relative concentrations of hepatic LCL species compared with LD diet-fed mice (P value = 0.004). Uncoupled mitochondria of mice fed the SO diet, compared with LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate-driven respiration (P values = 0.03 and 0.01). SO diet-fed mice had increased LA content in all phospholipid classes compared with LD-fed mice (P < 0.05).
CONCLUSIONS
Our findings reveal that maintaining or increasing hepatic LCL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher oleate content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.
Topics: Male; Mice; Animals; Linoleic Acid; Cardiolipins; Mitochondria; Dietary Fats; Fatty Acids; Liver; Diet; Phospholipids; Linoleic Acids; Respiration
PubMed: 38160803
DOI: 10.1016/j.tjnut.2023.12.037 -
BMC Genomics Dec 2023Safflower (Carthamus tinctorius L.) is an oilseed crop with substantial medicinal and economic value. However, the methods for constructing safflower core germplasm...
BACKGROUND
Safflower (Carthamus tinctorius L.) is an oilseed crop with substantial medicinal and economic value. However, the methods for constructing safflower core germplasm resources are limited, and the molecular mechanisms of lipid biosynthesis in safflower seeds are not well understood.
RESULTS
In this study, 11 oil-related quantitative traits and 50 pairs of InDel markers were used to assess the diversity of a collection of 605 safflower germplasms. The original safflower germplasm exhibited rich phenotypic diversity, with high variation for most of the phenotypic traits under investigation. Similarly, high genetic diversity was evaluated in the original germplasm, in which the mean Shannon's information index (I), observed heterozygosity (H), and expected heterozygosity (He) were 0.553, 0.182, and 0.374, respectively. Four subgroups with strong genetic structures were identified and a core germplasm of 214 cultivars was constructed, which is well represented in the original germplasm. Meanwhile, differential expression analysis of the transcriptomes of high and low linoleic acid safflower varieties at two stages of seed development identified a total of 47 genes associated with lipid biosynthesis. High expression of the genes KAS II and SAD enhanced the synthesis and accumulation of oleic acid, while FAD genes like FAD2 (Chr8G0104100), FAD3, FAD7 and FAD8 promoted the consumption of oleic acid conversion. The coordinated regulation of these multiple genes ensures the high accumulation of oleic acid in safflower seed oil.
CONCLUSIONS
Based on these findings, a core germplasm of 214 cultivars was constructed and 47 candidate genes related to unsaturated fatty acid biosynthesis and lipid accumulation were identified. These results not only provide guidance for further studies to elucidate the molecular basis of oil lipid accumulation in safflower seeds, but also contribute to safflower cultivar improvements.
Topics: Carthamus tinctorius; Oleic Acid; Phenotype; Seeds; Linoleic Acid
PubMed: 38082219
DOI: 10.1186/s12864-023-09874-5