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Biological & Pharmaceutical Bulletin 2021Long-chain acyl-CoA synthetases (ACSLs) are a family of enzymes that convert long-chain free fatty acids into their active form, acyl-CoAs. Recent knock-out mouse...
Long-chain acyl-CoA synthetases (ACSLs) are a family of enzymes that convert long-chain free fatty acids into their active form, acyl-CoAs. Recent knock-out mouse studies revealed that among ACSL isoenzymes, ACSL6 plays an important role in the maintenance of docosahexaenoic acid (DHA)-containing glycerophospholipids. Several transcript variants of the human ACSL6 gene have been found; the two major ACSL6 variants, ACSL6V1 and V2, encode slightly different short motifs that both contain a conserved structural domain, the fatty acid Gate domain. In the present study, we expressed recombinant human ACSL6V1 and V2 in Spodoptera frugiperda 9 (Sf9) cells using the baculovirus expression system, and then, using our novel ACSL assay system with liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined the substrate specificities of the recombinant human ACSL6V1 and V2 proteins. The results showed that both ACSL6V1 and V2 could convert various kinds of long-chain fatty acids into their acyl-CoAs. Oleic acid was a good common substrate and eicosapolyenoic acids were poor common substrates for both variants. However, ACSL6V1 and V2 differed considerably in their preferences for octadecapolyenoic acids, such as linoleic acid, and docosapolyenoic acids, such as DHA and docosapentaenoic acid (DPA): ACSL6V1 preferred octadecapolyenoic acids, whereas V2 strongly preferred docosapolyenoic acids. Moreover, our kinetic studies revealed that ACSL6V2 had a much higher affinity for DHA than ACSL6V1. Our results suggested that ACSL6V1 and V2 might exert different physiological functions and indicated that ACSL6V2 might be critical for the maintenance of membrane phospholipids bearing docosapolyenoic acids such as DHA.
Topics: Animals; Coenzyme A Ligases; Docosahexaenoic Acids; Enzyme Assays; Humans; Isoenzymes; Kinetics; Linoleic Acid; Phospholipids; Recombinant Proteins; Sf9 Cells; Spodoptera; Stearic Acids; Substrate Specificity; Tandem Mass Spectrometry
PubMed: 34602568
DOI: 10.1248/bpb.b21-00551 -
Frontiers in Nutrition 2023In the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported...
BACKGROUND
In the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported intake of trial foods from telephone interviews. The aim of this study was to evaluate compliance using objective dietary biomarkers for whole grain, fruit and vegetables, margarine and oil, seafood and overall fat quality, as well as reported intake from food records of key components of the study diets.
METHODS
Fifty patients with rheumatoid arthritis were randomized to begin with the intervention diet (rich in whole grain, fruit and vegetables, margarine/oil and seafood) or the control diet (rich in meat and high-fat dairy) for 10 weeks, followed by a ~ 4 months wash-out period, and then switched diet. Compliance was evaluated using plasma alkylresorcinols (AR) as biomarkers for intake of whole grain wheat and rye, serum carotenoids for fruit and vegetables, plasma linoleic acid (LA, 18:2 n-6) and -α-linolenic acid (18:3, n-3) for margarine and cooking oil, plasma eicosapentaenoic acid (EPA, 20:5 n-3), -docosahexaenoic acid (DHA 22:6, n-3) and -docosapentaenoic acid (22:5 n-3) for seafood, and plasma fatty acid pattern for the overall dietary fat quality. Reported intake of whole grain, fruit, berries and vegetables, seafood, red meat, and fat quality was extracted from 3-d food records.
RESULTS
Plasma AR C21:0 and C23:0, LA, EPA, and DHA were higher while total serum carotenoids were lower after the intervention diet period compared to the control diet period (AR and carotenoids: = <0.05, fatty acids: = <0.001). Reported intake of whole grain, fruit, berries and vegetables, and seafood was higher and reported intake of red meat was lower during the intervention diet period compared to the control diet period ( = <0.001). Plasma- and reported fatty acid pattern differed as intended between the diet periods.
CONCLUSION
This study indicates that the participants in the ADIRA trial were compliant to the study diets regarding intake of whole grain, cooking fat, seafood, and red meat, and the intended overall dietary fat quality. Compliance to instructions on fruit- and vegetable intake remains uncertain.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT02941055?term=NCT02941055&draw=2&rank=1, NCT02941055.
PubMed: 37426179
DOI: 10.3389/fnut.2023.1209787 -
Journal of Atherosclerosis and... Aug 2023To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii,...
AIM
To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors.
METHODS
Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis.
RESULTS
Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI.
CONCLUSIONS
Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.
Topics: Animals; Female; Humans; Male; Asian; Fatty Acids, Omega-3; Lipoproteins, HDL; Lipoproteins, LDL; Smoking; Adult; Middle Aged; Hawaii; East Asian People; Japan; Health Status
PubMed: 36328528
DOI: 10.5551/jat.63762 -
Bone Reports Dec 2021The osteoclast-dependent bone resorption process is a crucial part of the bone regulatory system. The excessive function of osteoclasts can cause diseases of bone,...
The osteoclast-dependent bone resorption process is a crucial part of the bone regulatory system. The excessive function of osteoclasts can cause diseases of bone, joint, and other tissues such as osteoporosis and osteoarthritis. Greenshell mussel oil (GSM), a good source of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs), was fractionated into total lipid, polar lipid, and non-polar lipid components and their anti-osteoclastogenic activity tested in RAW 264.7 cell cultures. Osteoclast differentiation process was achieved after 5 days of incubation with RANKL in 24-well culture plates. Introducing the non-polar lipid fraction into the culture caused a lack of cell differentiation, and a reduction in tartrate-resistant acid phosphatase (TRAP) activity and TRAP cell numbers in a dose-dependent manner (50% reduction at the concentration of 20 μg/mL, p < 0.001). Moreover, actin ring formation was significantly diminished by non-polar lipids at 10-20 μg/mL. The bone digestive enzymes released by osteoclasts into the pit formation were also compromised by downregulating gene expression of cathepsin K, carbonic anhydrase II (CA II), matrix metalloproteinase 9 (MMP-9), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). This study revealed that the non-polar lipid fraction of GSM oil contains bioactive substances which possess potent anti-osteoclastogenic activity.
PubMed: 34632003
DOI: 10.1016/j.bonr.2021.101132 -
Frontiers in Endocrinology 2022The pathogenesis of the progressive loss of beta cell function latent autoimmune diabetes in adults (LADA) remains still elusive. We aim to study the fatty acid (FA)...
BACKGROUND
The pathogenesis of the progressive loss of beta cell function latent autoimmune diabetes in adults (LADA) remains still elusive. We aim to study the fatty acid (FA) profile in LADA.
SUBJECTS AND METHODS
Data from 116 patients with diabetes and GADA and 249 diabetes controls without GADA selected by Propensity Score Matching were collected. FA was analyzed with liquid chromatography-tandem mass spectrometry analysis.
RESULTS
Principal factor analysis found component 1 explains 82.6% of total variance contained fatty acids from a mixed of lard oil, seafood, and vegetable diet, followed by diet predominantly from vegetable oil, a diet of high fat diet, and a diet of seafood diet. The FA heatmap looked clearly different among the three groups with more similar type 1 (t1dm) and LADA fatty acid profile. n-3 α-linolenic acid (ALA), n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), such as Eicosapentaenoic Acid and Docosapentaenoic Acid, n-3/n-6 ratio and triene/tetraene ratio were higher in patients with type 2 diabetes (t2dm) compared with LADA and t1dm. Saturated FAs were lower in t2dm than t1dm and LADA. Arachidic acid and n-6 LC-PUFAs were lower in t2dm than in t1dm and LADA. The characteristics of FAs in LADA were in between of classical t1dm and t2dm. Patients were classified into 6 clusters by FA clusters. Only cluster 2, 3, 5 contained enough patients to be analyzed. Cluster 5 showed an insulin deficient phenotype containing more than 60% of patients with t1dm and LADA and only 12.8% of t2dm. Cluster 2 and 3 were similar. β cell function and glycemic control was better in cluster 3 homing 25% of t2dm. Cluster 2 held 28% of t1dm and LADA, in this cluster more than 60% of patients was t2dm. n-3 linolenic acid, n-3 LC-PUFAs, some n-6 LC-PUFAs, n-3/n-6 ratio and triene/tetraene ratio were negatively associated with GADA positivity while n-6 Arachidonic Acid was associated positively with GADA. Similar findings were found for insulin sensitivity and beta cell function.
CONCLUSION
PUFA are associated with insulin sensitivity and beta cell function, and like other clinical features, FA profile distributed differently, but could not be used as makers to differentiate LADA from t1dm and t2dm.
ETHICS AND DISSEMINATION
This study has been approved by the Ethical Review Committee of Second Hospital of Dalian Medical University (approval number: 2021-005).
CLINICAL TRIAL REGISTRATION
none.
Topics: Autoantibodies; Autoimmunity; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fatty Acids; Glucose Intolerance; Glutamate Decarboxylase; Humans; Insulin Resistance; Latent Autoimmune Diabetes in Adults
PubMed: 35846301
DOI: 10.3389/fendo.2022.916981 -
Molecular Medicine Reports Sep 2022Ulcerative colitis (UC) is difficult to eradicate as it leads to chronic inflammation in the digestive tract due to immune system malfunction. The present study...
Ulcerative colitis (UC) is difficult to eradicate as it leads to chronic inflammation in the digestive tract due to immune system malfunction. The present study demonstrated the protective effect of 7S,15R‑dihydroxy‑16S,17S‑epoxy‑docosapentaenoic acid (diHEP‑DPA), which had been previously synthesized, on a dextran sulfate sodium (DSS)‑induced BALB/c mouse model of UC. UC was induced with 4% DSS drinking water for 7 days. Initially, the anti‑inflammatory effect of diHEP‑DPA was confirmed by demonstrating that lipopolysaccharide‑stimulated THP1 cells treated with diHEP‑DPA decreased IL‑6, TNF‑α and nitrite levels by fluorescence‑activated cell sorting (FACS) and Griess reagent kit. The results indicated that the administration of diHEP‑DPA at 20 µg/kg significantly reduced the severity of colitis, as determined by hematoxylin and eosin staining. The levels of TNF‑α, IL‑6 and IL‑1β in the colon tissue and serum were significantly reduced in the diHEP‑DPA + DSS‑treated group compared with in the control group, as determined by FACS and ELISA kit. It was also observed that diHEP‑DPA decreased myeloperoxidase (MPO) and nitrite levels in the colon tissues of diHEP‑DPA + DSS‑treated mice, as indicated using commercial MPO and nitric oxide kits. The diHEP‑DPA+DSS‑treated mice also exhibited decreased expression levels of phosporylated (p)‑inhibitor κB protein, p‑p65 and inducible nitric oxide synthase in the colon tissue by inhibiting inflammation, which were measured by reverse transcription‑quantitative PCR and weatern blot analysis. Overall, the present study demonstrated the protective effect of diHEP‑DPA against a severe colitis condition .
Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Acids, Unsaturated; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; NF-kappa B; Nitrites; Tumor Necrosis Factor-alpha
PubMed: 35856414
DOI: 10.3892/mmr.2022.12794 -
Frontiers in Immunology 2020Neuroinflammation plays a crucial role in the development and progression of Alzheimer's disease (AD), in which activated microglia are found to be associated with...
The Novel Omega-6 Fatty Acid Docosapentaenoic Acid Positively Modulates Brain Innate Immune Response for Resolving Neuroinflammation at Early and Late Stages of Humanized APOE-Based Alzheimer's Disease Models.
Neuroinflammation plays a crucial role in the development and progression of Alzheimer's disease (AD), in which activated microglia are found to be associated with neurodegeneration. However, there is limited evidence showing how neuroinflammation and activated microglia are directly linked to neurodegeneration . Besides, there are currently no effective anti-inflammatory drugs for AD. In this study, we report on an effective anti-inflammatory lipid, linoleic acid (LA) metabolite docosapentaenoic acid (DPAn-6) treatment of aged humanized EFAD mice with advanced AD pathology. We also report the associations of neuroinflammatory and/or activated microglial markers with neurodegeneration . First, we found that dietary LA reduced proinflammatory cytokines of IL1-β, IL-6, as well as mRNA expression of COX2 toward resolving neuroinflammation with an increase of IL-10 in adult AD models E3FAD and E4FAD mice. Brain fatty acid assays showed a five to six-fold increase in DPAn-6 by dietary LA, especially more in E4FAD mice, when compared to standard diet. Thus, we tested DPAn-6 in aged E4FAD mice. After DPAn-6 was administered to the E4FAD mice by oral gavage for three weeks, we found that DPAn-6 reduced microgliosis and mRNA expressions of inflammatory, microglial, and caspase markers. Further, DPAn-6 increased mRNA expressions of ADCYAP1, VGF, and neuronal pentraxin 2 in parallel, all of which were inversely correlated with inflammatory and microglial markers. Finally, both LA and DPAn-6 directly reduced mRNA expression of COX2 in amyloid-beta42 oligomer-challenged BV2 microglial cells. Together, these data indicated that DPAn-6 modulated neuroinflammatory responses toward resolution and improvement of neurodegeneration in the late stages of AD models.
Topics: Alzheimer Disease; Animals; Apolipoproteins E; Brain; Cytokines; Disease Models, Animal; Disease Susceptibility; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Immunity, Innate; Immunohistochemistry; Inflammation Mediators; Mice; Mice, Transgenic; Microglia; Neurodegenerative Diseases
PubMed: 33178186
DOI: 10.3389/fimmu.2020.558036 -
The Chinese Journal of Physiology 2023Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0%...
Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0% V̇O treadmill running) is optimal in protecting from exhaustive exercise-induced cardiac ischemic injury. This study is aimed to investigate the effect of long-term moderate exercise on myocardial metabolome in rats. Thirteen male Sprague-Dawley rats were randomly assigned into the control group (C) and the long-term moderate exercise group (E). The targeted metabolomics of the myocardium was analyzed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. Results showed that the metabolites categories of bile acids (BAs), fatty acids (FAs), and phenylpropanoic acids were significantly decreased. The biosynthesis of unsaturated FAs pathway was significantly downregulated. The altered metabolites in the E Group included decreased FAs (pentadecanoic acid, 10Z-heptadecenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, docosapentaenoic acid, and 10Z-nonadecenoic acid), decreased BAs (chenodeoxycholic acid and beta-muricholic acid), decreased organic acids (glycolic acid and 2-hydroxyglutaric acid), decreased carbohydrate (N-acetylneuraminic acid, Neu5Ac), decreased amino acids (α-aminobutyric acid and norvaline), decreased phenylpropanoic acids (hydroxyphenyllactic acid), and benzoic acids (4-hydroxybenzoic acid and phthalic acid). The results indicated that long-term moderate exercise has promoted lipids utilization in myocardium while exerted little influence on carbohydrate metabolism and diminished many detrimental metabolites. Notably, decrease of myocardial carbohydrate Neu5Ac after long-term moderate exercise might predict a prospective metabolomics biomarker for cardioprotection. This research has displayed the effect of long-term moderate exercise on myocardial metabolomic profiling in rats and indicated some promising metabolites which can be applied for exercise benefits in future.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Chromatography, Liquid; Prospective Studies; Tandem Mass Spectrometry; Metabolome; Myocardium; Carbohydrates
PubMed: 38149568
DOI: 10.4103/cjop.CJOP-D-23-00126 -
Frontiers in Nutrition 2024Depression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma...
BACKGROUND
Depression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma polyunsaturated fatty acids (PUFAs) levels and depression have yielded inconsistent results.
OBJECTIVE
To evaluate whether plasma n-3 and n-6 PUFAs levels are associated with depression in American adults.
METHODS
A cross-sectional study included 2053 adults (aged ≥20 y) in the National Health and Nutrition Examination Survey (NHANES), 2011-2012. The level of plasma n-3 and n-6 PUFAs were obtained for analysis. Self-reported Patient Health Questionnaire-9 (PHQ-9) was used to identify the depression status. Binary logistic regression analysis was performed to evaluate the association between quartiles of plasma n-3 and n-6 PUFAs and depression after adjustments for confounders.
RESULTS
The study of 2053 respondents over 20 years of age with a weighted depression prevalence of 7.29% comprised 1,043 men (weighted proportion, 49.13%) and 1,010 women (weighted, 50.87%), with a weighted mean (SE) age of 47.58 (0.67) years. Significantly increased risks of depression over non-depression were observed in the third quartiles (OR = 1.65, 95% CI = 1.05-2.62) for arachidonic acid (AA; 20:4n-6); the third quartiles (OR = 2.20, 95% CI = 1.20-4.05) for docosatetraenoic acid (DTA; 22:4n-6); the third (OR = 2.33, 95% CI = 1.34-4.07), and highest quartiles (OR = 1.83, 95% CI = 1.03-3.26) for docosapentaenoic acid (DPAn-6; 22:5n-6); and the third (OR = 2.18, 95% CI = 1.18-4.03) and highest quartiles (OR = 2.47, 95% CI = 1.31-4.68) for docosapentaenoic acid (DPAn-3; 22:5n-3); the second (OR = 2.13, 95% CI = 1.24-3.66), third (OR = 2.40, 95% CI = 1.28-4.50), and highest quartiles (OR = 2.24, 95% CI = 1.08-4.69) for AA/docosahexaenoic acid (DHA; 22:6n-3) ratio compared with the lowest quartile after adjusting for confounding factors.
CONCLUSION
Higher plasma levels of AA, DTA, DPAn-6, DPAn-3 PUFAs, and AA/DHA ratio may be potential risk factors for depression in US adults.
PubMed: 38544754
DOI: 10.3389/fnut.2024.1342304 -
The Journal of Nutrition Jul 2022Specialized pro-resolving mediators (SPMs), synthesized from PUFAs, resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the... (Clinical Trial)
Clinical Trial
BACKGROUND
Specialized pro-resolving mediators (SPMs), synthesized from PUFAs, resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the SPM biosynthetic pathway may have potential health benefits for select clinical populations, such as subjects with obesity who display dysregulation of SPM metabolism. However, the concentrations of SPMs and their metabolic intermediates in humans with obesity remains unclear.
OBJECTIVES
The primary objective of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. The second objective was to determine if the supplement changed the relative abundance of key immune cell populations. Finally, given the critical role of antibodies in inflammation, we determined if ex vivo CD19 + B-cell antibody production was modified by marine oil intervention.
METHODS
Twenty-three subjects [median age: 56 y; BMI (in kg/m2): 33.1] consumed 2 g/d of a marine oil supplement for 28-30 d. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic (HEPE), 14-hydroxydocosahexaenoic acid (14-HDHA), and 17-HDHA. Blood was collected pre- and postsupplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B-cell isolation. Paired t-tests and Wilcoxon tests were used for statistical analyses.
RESULTS
Relative to preintervention, the supplement increased 6 different HEPEs and HDHAs accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 concentrations were increased 3.5- and 4.7-fold upon intervention, respectively. The supplement did not increase the concentration of D-series resolvins and had no effect on the abundance of immune cells. Ex vivo B-cell IgG but not IgM concentrations were lowered postsupplementation.
CONCLUSIONS
A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased concentrations of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov as NCT04701138.
Topics: Adult; Dietary Supplements; Docosahexaenoic Acids; Fatty Acids, Omega-3; Humans; Inflammation; Inflammation Mediators; Middle Aged; Obesity; Plasma
PubMed: 35349683
DOI: 10.1093/jn/nxac075