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Frontiers in Aging Neuroscience 2023Observational studies demonstrated controversial effect of polyunsaturated fatty acids (PUFAs) on Parkinson's disease (PD) with limited causality evidence. Randomized...
INTRODUCTION
Observational studies demonstrated controversial effect of polyunsaturated fatty acids (PUFAs) on Parkinson's disease (PD) with limited causality evidence. Randomized control trials showed possible improvement in PD symptoms with PUFA supplement but had small study population and limited intervention time.
METHODS
A two-sample Mendelian randomization was designed to evaluate the causal relevance between PUFAs and PD, using genetic variants of PUFAs as instrumental variables and PD data from the largest genome-wide association study as outcome. Inverse variance weighted (IVW) method was applied to obtain the primary outcome. Mendelian randomization Egger regression, weighted median and weighted mode methods were exploited to assist result analyses. Strict Mendelian randomization and multivariable Mendelian randomization (MVMR) were used to estimate direct effects of PUFAs on PD, eliminating pleiotropic effect. Debiased inverse variance weighted estimator was implemented when weak instrument bias was introduced into the analysis. A variety of sensitivity analyses were utilized to assess validity of the results.
RESULTS
Our study included 33,674 PD cases and 449,056 controls. Higher plasma level of arachidonic acid (AA) was associated with a 3% increase of PD risk per 1-standard deviation (SD) increase of AA (IVW; Odds ratio (OR)=1.03 [95% confidence interval (CI) 1.01-1.04], = 2.24E-04). After MVMR (IVW; OR=1.03 [95% CI 1.02-1.04], =6.15E-08) and deletion of pleiotropic single-nucleotide polymorphisms overlapping with other lipids (IVW; OR=1.03 [95% CI 1.01-1.05], =5.88E-04), result was still significant. Increased level of eicosapentaenoic acid (EPA) showed possible relevance with increased PD risk after adjustment of pleiotropy (MVMR; OR=1.05 [95% CI 1.01-1.08], =5.40E-03). Linoleic acid (LA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were found not causally relevant to PD risk. Various sensitivity analyses verified the validity of our results. In conclusion, our findings from Mendelian randomization suggested that elevated levels of AA and possibly EPA might be linked to a higher risk of PD. No association between PD risk and LA, DHA, DPA, or ALA was found.
DISCUSSION
The odds ratio for plasma AA and PD risk was weak. It is important to approach our results with caution in clinical practice and to conduct additional studies on the relationship between PUFAs and PD risk.
PubMed: 36909950
DOI: 10.3389/fnagi.2023.1123239 -
Animals : An Open Access Journal From... Feb 2023Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have special physiological functions in both brain and retinal tissues that are related to the modulation of inflammatory...
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have special physiological functions in both brain and retinal tissues that are related to the modulation of inflammatory processes and direct effects on neuronal membrane fluidity, impacting mental and visual health. Among them, the long-chain (LC) n-3 PUFAs, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are of special importance. Scarce data are available about the fatty acid (FA) composition of the ruminant brain in response to dietary intervention. However, we decided to examine the brain and retina FA composition of lambs supplemented with an EPA-rich microalga feed for 21 days, as it is known that despite the extensive biohydrogenation of dietary PUFAs in the rumen, ruminants can selectively accumulate some n-3 LC-PUFAs in their brain and retinal tissues. Twenty-eight male lambs were fed a control diet, or the same diet further supplemented with sp. microalga. Their brains and retina were collected for FA characterization. Overall, the brain FA profile remained unchanged, with little alteration in omega-3 docosapentaenoic acid (DPA) enhancement in both the hippocampus and prefrontal cortex. Retinal tissues were particularly responsive to the dietary intervention, with a 4.5-fold enhancement of EPA in the freeze-dried-fed lambs compared with the control lambs. We conclude that retinal tissues are sensitive to short-term n-3 PUFA supplementation in lambs.
PubMed: 36899687
DOI: 10.3390/ani13050828 -
Environmental Research May 2023Intake of fish and seafood during pregnancy may have certain beneficial effects on fetal development, but measurement of intake using questionnaires is unreliable. Here,...
Intake of fish and seafood during pregnancy may have certain beneficial effects on fetal development, but measurement of intake using questionnaires is unreliable. Here, we assessed several candidate biomarkers of seafood intake, including long-chain omega 3 fatty acids (n-3 LCPUFA), selenium, iodine, methylmercury, and different arsenic compounds, in 549 pregnant women (gestational week 29) in the prospective birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Proportions of the fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in erythrocytes were measured using gas chromatography with flame ionization detector. Selenium was measured in blood plasma and erythrocytes, mercury and arsenic in erythrocytes, and iodine and several arsenic compounds in urine, using inductively coupled plasma mass spectrometry, arsenic compounds after first being separated by ion exchange high-performance liquid chromatography (HPLC). Each biomarker was related to intake of total seafood and to intake of fatty and lean fish, and shellfish in third trimester, estimated from a semi-quantitative food frequency questionnaire filled out in gestational week 34. The pregnant women reported a median total seafood intake of 184 g/week (5th-95th percentiles: 34-465 g/week). This intake correlated most strongly with erythrocyte mercury concentrations (rho = 0.49, p < 0.001), consisting essentially of methylmercury, followed by total arsenic in erythrocytes (rho = 0.34, p < 0.001), and arsenobetaine in urine (rho = 0.33, p < 0.001), the main form of urinary arsenic. These biomarkers correlated well with intake of both fatty fish, lean fish, and shellfish. Erythrocyte DHA and plasma selenium correlated, although weakly, mainly with fatty fish (rho = 0.25 and 0.22, respectively, both p < 0.001). In conclusion, elevated concentrations of erythrocyte mercury and urinary arsenobetaine can be useful indicators of seafood intake, more so than the n-3 LCPUFAs. However, the relative importance of the biomarkers may differ depending on the type and amount of seafood consumed.
Topics: Animals; Pregnancy; Female; Humans; Arsenic; Methylmercury Compounds; Fatty Acids; Selenium; Prospective Studies; Environmental Pollutants; Micronutrients; Fatty Acids, Omega-3; Arsenicals; Mercury; Seafood; Fishes; Iodine; Biomarkers
PubMed: 36878269
DOI: 10.1016/j.envres.2023.115576 -
International Journal of Molecular... Feb 2023Daily exposure to bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of...
Daily exposure to bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of polyunsaturated fatty acids necessary for sperm maturity, motility, and spermatogenesis. Whether prenatal exposure to bisphenols alters testicular fatty acid metabolism in adult offspring is unknown. Pregnant Wistar rats were gavaged from gestational day 4 to 21 with BPA and BPS (0.0, 0.4, 4.0, 40.0 μg/kg bw/day). Despite increased body and testis weight, the total testicular cholesterol, triglyceride, and plasma fatty acids were unaffected in the offspring. Lipogenesis was upregulated by increased SCD-1, SCD-2, and expression of lipid storage (ADRP) and trafficking protein (FABP4). The arachidonic acid, 20:4 n-6 (ARA) and docosapentaenoic acid, 22:5 n-6 (DPA) levels were decreased in the BPA-exposed testis, while BPS exposure had no effects. The expression of PPARα, PPARγ proteins, and CATSPER2 mRNA were decreased, which are important for energy dissipation and the motility of the sperm in the testis. The endogenous conversion of linoleic acid,18:2 n-6 (LA), to ARA was impaired by a reduced ARA/LA ratio and decreased FADS1 expression in BPA-exposed testis. Collectively, fetal BPA exposure affected endogenous long-chain fatty acid metabolism and steroidogenesis in the adult testis, which might dysregulate sperm maturation and quality.
Topics: Animals; Female; Humans; Male; Pregnancy; Rats; Benzhydryl Compounds; Calcium Channels; Endocrine Disruptors; Fatty Acids; Prenatal Exposure Delayed Effects; Proteins; Rats, Wistar; Semen; Seminal Plasma Proteins; Sperm Maturation; Testis
PubMed: 36835180
DOI: 10.3390/ijms24043769 -
Antioxidants (Basel, Switzerland) Feb 2023The high propensity of dietary polyunsaturated fatty acids (PUFA) to oxidation can induce a cascade of cellular immune-oxidative imbalances. On the other hand, PUFA,...
The high propensity of dietary polyunsaturated fatty acids (PUFA) to oxidation can induce a cascade of cellular immune-oxidative imbalances. On the other hand, PUFA, namely docosapentaenoic acid (ω6-DPA) and docosahexaenoic acid (DHA) can exert immunomodulatory effects by suppressing a pro-inflammatory response. Thus, the objective of this study was to investigate the effect of dietary supplementation with spp. levels, rich in both ω6-DPA and DHA on the transcriptional profiling of genes involved in oxidative homeostasis and innate immunity of dairy goats' monocytes and neutrophils. Twenty-four dairy goats were divided into four homogeneous sub-groups; the diet of the control group (CON) had no spp. while those of the treated groups were supplemented daily with 20 (ALG20), 40 (ALG40), and 60 (ALG60) g/goat/day. The mRNA levels of in neutrophils were downregulated ( = 0.037), while in monocytes, and were downregulated ( = 0.010 and = 0.044, respectively) in ALG60 compared to the CON group. mRNA levels were downregulated ( = 0.036) in ALG20 and ALG60 compared to the CON group in neutrophils. was upregulated ( = 0.043) in the neutrophiles of ALG60-goats. was upregulated ( = 0.042) in the monocytes of ALG40-fed goats, while higher ( = 0.045) levels were also found in the ALG60 group in neutrophils. The mRNA levels of were downregulated ( = 0.035) in monocytes of the ALG40 and ALG60 groups. The mRNA levels of were also downregulated ( = 0.004) in monocytes of -fed goats, while in neutrophils, significant downregulation ( = 0.024) was only found for ALG60 compared to the CON group. mRNA levels were significantly decreased ( = 0.033) in ALG60 compared to the CON group in monocytes. mRNA levels were increased ( = 0.015) in ALG60 compared to ALG20 and ALG40 groups in monocytes, while in neutrophils, a significant downregulation ( = 0.028) was observed in ALG20 compared to the CON group. The inclusion of more than 20 g spp./day in goats' diet induced imbalances in mechanisms that regulate the antioxidant system, while downregulated the expression of pro-inflammatory pathways in monocytes and neutrophils.
PubMed: 36830055
DOI: 10.3390/antiox12020497 -
Marine Drugs Jan 2023Although the tumor bulk is initially reduced by 5-fluorouracil (5-FU), chemoresistance developed due to prolonged chemotherapy in colorectal cancer (CRC). The enrichment...
7,15-Dihydroxy-16,17-epoxy-docosapentaenoic Acid Overcomes Chemoresistance of 5-Fluorouracil by Suppressing the Infiltration of Tumor-Associated Macrophages and Inhibiting the Activation of Cancer Stem Cells in a Colorectal Cancer Xenograft Model.
Although the tumor bulk is initially reduced by 5-fluorouracil (5-FU), chemoresistance developed due to prolonged chemotherapy in colorectal cancer (CRC). The enrichment of cancer stem cells (CSCs) and the infiltration of tumor-associated macrophages (TAMs) contribute to chemoresistance and poor outcomes. A docosahexaenoic acid derivative developed by our group, 7,15-dihydroxy-16,17-epoxy-docosapentaenoic acid (diHEP-DPA), exerts antitumor effects against TAMs infiltration and CSCs enrichment in our previous study. The current study aimed to investigate whether diHEP-DPA was able to overcome chemoresistance to 5-FU in CRCs, together with the potential synergistic mechanisms in a CT26-BALB/c mouse model. Our results suggested that although 5-FU inhibited tumor growth, 5-FU enriched CSCs via the WNT/β-catenin signaling pathway, resulting in chemoresistance in CRCs. However, we revealed that 5-FU promoted the infiltration of TAMs via the NF-kB signaling pathway and improved epithelial-mesenchymal transition (EMT) via the signal transducer and activator of the transcription 3 (STAT3) signaling pathway; these traits were believed to contribute to CSC activation. Furthermore, supplementation with diHEP-DPA could overcome drug resistance by decreasing the CSCs, suppressing the infiltration of TAMs, and inhibiting EMT progression. Additionally, the combinatorial treatment of diHEP-DPA and 5-FU effectively enhanced phagocytosis by blocking the CD47/signal regulatory protein alpha (SIRPα) axis. These findings present that diHEP-DPA is a potential therapeutic supplement to improve drug outcomes and suppress chemoresistance associated with the current 5-FU-based therapies for colorectal cancer.
Topics: Mice; Animals; Humans; Fluorouracil; Drug Resistance, Neoplasm; Tumor-Associated Macrophages; Heterografts; Cell Line, Tumor; Colorectal Neoplasms; Wnt Signaling Pathway; Neoplastic Stem Cells
PubMed: 36827121
DOI: 10.3390/md21020080 -
Frontiers in Veterinary Science 2023Artificial insemination (AI) is an effective reproductive technique to improve the performance of cashmere goats and prevent the spread of diseases, and the quality of...
BACKGROUND
Artificial insemination (AI) is an effective reproductive technique to improve the performance of cashmere goats and prevent the spread of diseases, and the quality of the semen determines the success of AI. The potential of leaf powder (MOLP) and leaf ethanolic extract (MOLE) to improve semen quality has been reported, but the underlying mechanisms remain unclear. For the purpose, 18 mature male cashmere goats were randomly assigned into three groups: the control (CON), MOLP, and MOLE groups. The CON group received distilled water orally; the MOLP group was orally treated with 200 mg/kg body weight (BW) MOLP; and the MOLE group was orally treated with 40 mg/kg BW MOLE.
RESULTS
Results showed that MOLE contained long-chain fatty acids and flavonoids. Treatment with MOLP and MOLE increased the activities of the serum catalase, superoxide dismutase, and glutathione peroxidase ( < 0.05), enhanced the total antioxidant capacity ( < 0.05), and reduced the serum malondialdehyde level ( < 0.05). At the same time, MOLE increased the contents of serum gonadotropin releasing hormone and testosterone ( < 0.05). Moreover, MOLE significantly increased sperm concentration, motility, and viability ( < 0.05). Meanwhile, MOLE raised the Chao1 index ( < 0.05) and altered the composition of the rumen microbiota; it also raised the relative abundance of ( < 0.05) and ( < 0.05) and reduced the relative abundance of ( < 0.1). Correlation analysis revealed the genus was significantly negatively correlated with sperm concentration, as well as sperm motility and viability. Furthermore, MOLE significantly increased the rumen levels of the steroid hormones testosterone and dehydroepiandrosterone ( < 0.05), as well as the polyunsaturated fatty acids (PUFAs) alpha-Linolenic acid, gamma-Linolenic acid, docosapentaenoic acid, and 9-S-Hydroperoxylinoleicacid ( < 0.05).
CONCLUSIONS
Oral MOLE supplementation can improve semen quality by increasing the antioxidant capacity and altering the rumen microbiota and metabolites of cashmere goats. Moreover, the MOLP supplementation could enhance the antioxidant capacity of cashmere goats.
PubMed: 36777668
DOI: 10.3389/fvets.2023.1049093 -
Journal of Alzheimer's Disease : JAD 2024Mild cognitive impairment (MCI) is the prodromal stage of dementia. In this stage, reasonable intervention measures can help to delay the decline of cognitive function.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mild cognitive impairment (MCI) is the prodromal stage of dementia. In this stage, reasonable intervention measures can help to delay the decline of cognitive function. Supplementation of n-3 polyunsaturated fatty acids (n-3PUFAs) may be beneficial to delay the decline of cognitive function in the elderly.
OBJECTIVE
To investigate the effectiveness of docosapentaenoic acid (DHA) or/and eicosapentaenoic acid (EPA) supplements in the elderly with MCI.
METHODS
Eight electronic databases, PubMed, Cochrane Library, Embase, VIP, SinoMed, Web of Science, CNKI, and WANFANG DATA, were searched for related articles from inception until January 2022. Subgroup analyses and sensitivity analyses were performed to detect confounding variables. Standardized mean differences (SMD) with 95% confidence intervals (CI) were determined. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots. Stata12.0 was used for Begg's and Egger's test to quantify whether publication bias. Linear relationship between global cognition and covariates was examined in meta-regression analysis.
RESULTS
Twelve studies (n = 1,124) were included. The methodological quality of research is mostly medium. Compared with placebo, n-3PUFAs supplements have benefits on global cognition [SMD = 0.51, 95% CI(0.12, 0.91), p = 0.01]. No significant differences were observed between intervention group and placebo on language fluency, executive functions, and depression.
CONCLUSION
Our findings indicated DHA and/or EPA supplements have benefits on global cognition, and it may also reduce the level of blood amyloid-β (Aβ)-related biomarkers (e.g., Aβ40, Aβ42) and inflammatory factors (e.g., 1L-6, 1L-10). Since there are only two relative articles, more research is needed in the future to clarify the relationship.
Topics: Humans; Cognitive Dysfunction; Fatty Acids, Omega-3; Dietary Supplements; Aged; Eicosapentaenoic Acid; Fatty Acids, Unsaturated
PubMed: 36776054
DOI: 10.3233/JAD-220863 -
Nutrients Feb 2023Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk.
METHODS
We systematically searched Embase and Medline databases to identify eligible studies that examined the associations of different types of Fas with CRC risk. The effect estimates and their 95% confidence intervals (Cis) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to examine the robustness of the study findings.
RESULTS
This study evaluated the associations of 28 dietary and 18 blood Fas with CRC risk by summarizing the most updated evidence from 54 observational and four Mendelian Randomization (MR) studies. The present findings suggested that high dietary intake of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), and docosapentaenoic acid (DPA) are related to low risk of CRC, while the -6/-3 PUFA ratio and trans-FA are related to high risk of CRC. The summary of all cohort studies found that a high intake of SFA and DHA was a protective factor for CRC, and a high intake of the -6/-3 PUFA ratio was a risk factor for CRC. In the subgroup analysis of cancer subsites, we found that the dietary intake of linoleic acid (LA) and trans-FA are risk factors, while DPA is a protective factor for colon cancer. High dietary DHA intake was associated with a lower risk of rectal cancer, while the dietary -6/-3 PUFA ratio was associated with a higher risk of rectal cancer. Meta-analysis of blood FA levels showed a significant reverse association between blood pentadecanoic acid and CRC risk, whilst other blood Fas showed no significant association with CRC risk. All included MR studies showed that high plasma arachidonic acid (AA) is associated with increased CRC risk.
CONCLUSIONS
Current evidence on the dietary intake and blood levels of Fas in relation to CRC risk is less consistent. Future studies are needed to investigate how the metabolism of Fas contributes to CRC development.
Topics: Humans; Fatty Acids; Fatty Acids, Omega-3; Eating; Risk Factors; Colorectal Neoplasms; Rectal Neoplasms; Observational Studies as Topic
PubMed: 36771436
DOI: 10.3390/nu15030730 -
Progress in Lipid Research Jul 2023This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA... (Review)
Review
This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA into the developing brain of rat pups, its conservation as a principal component in the brains of 32 mammalian species and the high proportion delivered by the human placenta for foetal nutrition, compared to its parent linoleic acid (LA). ArA is quantitatively the principal acyl component of membrane lipids from foetal red cells, mononuclear cells, astrocytes, endothelium, and placenta. Functionally, we present evidence that ArA, but not DHA, relaxes the foetal mesenteric arteries. The placenta biomagnifies ArA, doubling the proportion of the maternal level in cord blood. The proportions of ArA and its allies (di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid) are similar or higher than the total of ω3 fatty acids in human milk, maintaining the abundant supply to the developing infant. Despite the evidence of the importance of ArA, the European Food Standard Agency, in 2014 rejected the joint FAO and WHO recommendation on the inclusion of ArA in infant formula, although they recommended DHA. The almost universal dominance of ArA in the membrane phosphoglycerides during human organogenesis and prenatal growth suggests that the importance of ArA and its allies in reproductive biology needs to be re-evaluated urgently.
Topics: Pregnancy; Female; Humans; Animals; Rats; Arachidonic Acid; Docosahexaenoic Acids; Linoleic Acid; Infant Formula; Glycerophospholipids; Mammals
PubMed: 36746351
DOI: 10.1016/j.plipres.2023.101222