Search Results (33)

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to dietary fat quality and polyunsaturated fatty-acid metabolism. We evaluated whether dietary n-6 fatty-acid intake, serum dihomo-γ-linolenic acid (DGLA), and desaturase-based indices for Δ5-desaturase (D5D) and Δ6-desaturase (D6D) are associated with MASLD. Methods: We conducted a cross-sectional analysis within the HOZUGAWA health checkup cohort in Japan (n = 289; 100 MASLD, 189 non-MASLD). Participants underwent hepatic ultrasonography, dietary assessment using the Brief Self-Administered Diet History Questionnaire, and fasting serum metabolomics by gas chromatography–mass spectrometry with solid-phase dehydration derivatization. Enzyme indices were defined as the D5D index = arachidonic acid/DGLA and the D6D proxy index = DGLA/linoleic acid (hereafter referred to as the D6D index) because γ-linolenic acid was not measured. Natural-log-transformed D5D index, D6D index, DGLA, and total dietary n-6 fatty-acid intake were entered into multivariable logistic regression models for MASLD adjusted for age, sex, BMI, alcohol intake, and total energy. Results: Compared with non-MASLD, MASLD showed higher serum DGLA, lower D5D index, and higher D6D index (all p ≤ 0.005), with no between-group differences in total energy intake, linoleic acid, total polyunsaturated fatty acids, or total dietary n-6 fatty-acid intake. Higher ln D5D was independently associated with lower odds of MASLD (OR 0.62, 95% CI 0.42–0.86), whereas higher ln D6D index (OR 1.42, 95% CI 1.04–1.95) and ln DGLA (OR 1.62, 95% CI 1.13–2.43) were each positively associated. Total dietary n-6 fatty-acid intake was not independently associated with MASLD. Conclusions: In this Japanese health examination cohort, an imbalance in estimated desaturase activities—lower D5D index and higher D6D index—together with higher serum DGLA was independently associated with MASLD, whereas n-6 intake showed no group difference or independent association. These findings suggest that enzyme-linked endogenous n-6 metabolic status may be more closely related to the MASLD phenotype than intake quantity alone. Full article

Arachidonic acid levels are elevated in the colonic mucosa of patients with inflammatory bowel disease (IBD). Fecal metabolites are emerging as valuable diagnostic tools for IBD. This study aimed to investigate associations between 31 fecal fatty acids, including arachidonic acid, to identify potential correlations with disease severity. Among the 31 fatty acids analyzed in feces, dihomo-γ-linolenic acid, arachidonic acid, and adrenic acid were significantly increased in patients with IBD compared to controls. In contrast, levels of linoleic acid and γ-linolenic acid, the precursors of arachidonic acid, were similar between both groups. No significant differences in fatty acid levels were observed between patients with Crohn’s disease and ulcerative colitis. Arachidonic acid and adrenic acid levels positively correlated with fecal calprotectin, a clinically established marker of IBD severity, but showed no association with stool consistency or the Gastrointestinal Symptom Rating Scale. This suggests that these fatty acids are linked to disease severity rather than disease-related symptoms. Current IBD-specific medications had no significant impact on the fecal levels of any of the 31 fatty acids. In summary, this study demonstrates elevated fecal levels of dihomo-γ-linolenic acid, arachidonic acid, and adrenic acid in IBD patients. Normal levels of precursor fatty acids suggest that impaired downstream metabolism may contribute to the accumulation of these n-6 polyunsaturated fatty acids. Full article

Wollemi pine, Wollemia nobilis W. G. Jones, K. D. Hill & J. M. Allan (Araucariaceae) was discovered in a remote canyon 150 km north-west of Sydney, Australia. As fewer than 100 adult trees of this plant survive in the wild, efforts to conserve this species have included seed storage. Fresh and stored seeds were analysed for yield and composition of the seed oil. The seed kernels, from both fresh and stored seed, were rich in oil with contents of 42% and 48%, respectively. The fatty acid profile of Wollemi pine seed oil was determined by GC-MS analyses of fatty acid methyl ester derivatives. Oleic acid makes up 32% of the fatty acid profile, while the major polyunsaturated fatty acid is linoleic acid (25%). Most of the detectable omega-3 fatty acid content of the oil is α-linolenic acid (3%). The seed oil has a high content of C20 to C24 fatty acids (25%) consisting of long-chain saturated fatty acids (19%). The polyunsaturated C20 omega-6 fatty acid content consists of eicosadienoic acid, dihomo-γ-linolenic acid, and arachidonic acid (total 4%). ¹H NMR analyses of the intact oil showed that the lipids were largely in the form of triglycerides with a degree of unsaturation of 1.5 double bond equivalents per fatty acid residue. In artificially aged or stored seeds, minor additional ¹H NMR spectral signals were attributed to an omega-3 epoxylipid, tentatively identified as cis-15,16-epoxy-9Z,12Z-octadecadienoic acid or ester derivative. Other minor signals were characteristic of a hydroxy or a hydroperoxy E,Z diene containing fatty acid. These products are typically formed by metabolic lipid oxidation of fatty acids. The content of the omega-3 epoxylipid, determined by the ¹H NMR method, varied with storage conditions and duration from less than 0.1% to a maximum of 3.3%. Full article

Inulin may be a promising therapeutic molecule for treating non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its therapeutic activity remain unclear. To address this issue, a high-fat-diet-induced NAFLD mouse model was developed and treated with inulin. The NAFLD phenotype was evaluated via histopathological analysis and biochemical parameters, including serum levels of alanine aminotransferase, aspartate aminotransferase, liver triglycerides, etc. A serum metabolomics study was conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry. The results revealed that inulin mitigated NAFLD symptoms such as histopathological changes and liver cholesterol levels. Through the serum metabolomics study, 347 differential metabolites were identified between the model and control groups, and 139 differential metabolites were identified between the inulin and model groups. Additionally, 48 differential metabolites (such as phosphatidylserine, dihomo-γ-linolenic acid, L-carnitine, and 13-HODE) were identified as candidate targets of inulin and subjected to pathway enrichment analysis. The results revealed that these 48 differential metabolites were enriched in several metabolic pathways such as fatty acid biosynthesis and cardiolipin biosynthesis. Taken together, our results suggest that inulin might attenuate NAFLD partially by modulating 48 differential metabolites and their correlated metabolic pathways, constituting information that might help us find novel therapies for NAFLD. Full article

Fatty acid desaturase 1 (FADS1) is a rate-limiting enzyme in long-chain polyunsaturated fatty acid (LCPUFA) synthesis. Reduced activity of FADS1 was observed in metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to determine whether adeno-associated virus serotype 8 (AAV8) mediated hepatocyte-specific overexpression of Fads1 (AAV8-Fads1) attenuates western diet-induced metabolic phenotypes in a rat model. Male weanling Sprague-Dawley rats were fed with a chow diet, or low-fat high-fructose (LFHFr) or high-fat high-fructose diet (HFHFr) ad libitum for 8 weeks. Metabolic phenotypes were evaluated at the endpoint. AAV8-Fads1 injection restored hepatic FADS1 protein levels in both LFHFr and HFHFr-fed rats. While AAV8-Fads1 injection led to improved glucose tolerance and insulin signaling in LFHFr-fed rats, it significantly reduced plasma triglyceride (by ~50%) and hepatic cholesterol levels (by ~25%) in HFHFr-fed rats. Hepatic lipidomics analysis showed that FADS1 activity was rescued by AAV8-FADS1 in HFHFr-fed rats, as shown by the restored arachidonic acid (AA)/dihomo-γ-linolenic acid (DGLA) ratio, and that was associated with reduced monounsaturated fatty acid (MUFA). Our data suggest that the beneficial role of AAV8-Fads1 is likely mediated by the inhibition of fatty acid re-esterification. FADS1 is a promising therapeutic target for MASLD in a diet-dependent manner. Full article

Background: Adipokines, as well as the fatty acid profile of red blood cell (RBC) membranes, are known to play important roles in the development and progression of metabolic complications induced by obesity. Thus, the objective of this study is to compare the serum adipokine profile and the RBC membrane fatty acid profile of normal-weight and obese adults, and to analyze their relationship with serum biochemical parameters. Methods: An observational case–control study was performed in 75 normal-weight and obese adult subjects. Biochemical serum parameters, eight serum adipokines and the RBC membrane fatty acid profiles were measured. Associations between parameters were established using regression analysis. Results: Subjects with obesity showed increased levels of leptin, fibroblast growth factor 21 (FGF21) and overexpressed nephroblastoma (NOV/CCN3), decreased adiponectin, and similar levels of vaspin and chemerin compared to normal-weight subjects. Significant positive and negative correlations were found with triglycerides and high-density lipoprotein-cholesterol (HDL-c), respectively. An increase in the total ω-6 fatty acids in the RBC membrane fatty acid profiles in subjects with obesity was observed, because of higher levels of both dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), and decreased total ω-3 fatty acids, mainly due to lower levels of docosahexaenoic acid (DHA). The ω-6/ω-3 ratio in the RBCs was significantly higher, suggesting an inflammatory status, as was also suggested by a reduced adiponectin level. A negative association between DGLA and adiponectin, and a positive association between DHA and serum triglycerides, was observed. Conclusions: Important alterations in serum adipokine and RBC fatty acid profiles are found in subjects with obesity. Full article

Dihomo-γ-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid that has been shown to have anti-inflammatory and anti-allergic effects in mice and cell study. To date, however, no human intervention study has examined the effects of DGLA. Therefore, we investigated the effects of DGLA on pollen-induced allergic symptoms in healthy adults. We performed a randomized, double-blind, placebo-controlled, parallel-group study comprising healthy Japanese men and women. Each subject received four 250 mg capsules providing 314 mg DGLA/day (DGLA group, n = 18) or olive oil (placebo group, n = 15) for 15 weeks. The primary outcomes, classification of the severity of allergic rhinitis symptoms (CSARS), and the Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ) served as symptom scores during the pollen season. In the DGLA group, the cedar pollen associated symptoms of sneezing and a blocked nose in the CSARS were significantly lower than those in the placebo group (p < 0.05, p < 0.01, respectively). Significant trends were observed the symptoms of runny nose in the CSARS and total symptom score (TSS) in the JRQLQ for cedar pollen (p < 0.1). To our knowledge, this is the first study to report the effects of DGLA in humans, and the results suggest that DGLA is effective in reducing allergic symptoms caused by pollen. Full article

Fatty acids (FAs) are important regulators of immune responses and innate defense mechanisms. We hypothesized that disturbed FA metabolism could contribute to the progression of HIV infection. Plasma levels of 45 FAs were analyzed with gas chromatography in healthy controls and HIV-infected patients with regard to Mycobacterium avium complex (MAC) infection. In vitro, we assessed MAC-PPD-induced release of inflammatory cytokines in peripheral and bone marrow mononuclear cells (PBMC and BMMC) according to levels of n-6 polyunsaturated fatty acids (PUFAs). While plasma saturated FAs were higher in HIV infection, PUFAs, and in particular the n-6 PUFA arachidonic acid (AA), were lower in patients with advanced disease. The ratio between AA and precursor dihomo-γ-linolenic acid, reflecting Δ5-desaturase activity, was markedly lower and inversely correlated with plasma HIV RNA levels in these patients. Depletion of AA was observed prior to MAC infection, and MAC-PPD-induced release of TNF and IL-6 in PBMC and BMMC was lower in patients with low plasma AA. Our findings suggest that dysregulated metabolism of n-6 PUFAs may play a role in the progression of HIV infection. While high AA may contribute to chronic inflammation in asymptomatic HIV-infected patients, low AA seems to increase the susceptibility to MAC infection in patients with advanced disease. Full article

The aim of our study was to investigate the effects of a shortened daily photoperiod on anxiety-like behaviour, brain oxidative stress, lipid status and fatty acid composition of serum lipids in a streptozotocin (STZ)-induced model of diabetes mellitus in rats. Male Wistar rats were divided into the following groups: first group—control group (C_12/12); second group—diabetic group (DM_12/12; 100 mg/kg STZ); third group—control group exposed to a light/dark cycle 6/18 h (C_6/18); fourth group—diabetic group exposed to a light/dark cycle 6/18 h (DM_6/18). Anxiety-like behaviour was tested three weeks following STZ injection by elevated plus maze (EPM) and open-field test (OFT). Oxidative stress parameters were measured in the cortex, hippocampus and thalamus, while lipid status and fatty acid methyl esters (FAMEs) were measured in the serum. Both EPM and OFT showed a lower degree of anxiety-like behaviour in the DM_6/18 vs. DM_12/12 group. Lipid peroxidation in the cortex, hippocampus and thalamus was significantly lower in the DM_6/18 vs. DM_12/12 group (p < 0.05), associated with an increased level of antioxidant enzymes and protein thiols in the cortex and thalamus. In the DM_6/18 group, oleic, vaccenic, dihomo-γ-linolenic and docosahexaenoic acid concentrations were significantly higher in comparison to the DM_12/12 group. A shortened daily photoperiod alleviates anxiety-like behaviour in diabetic rats by reduced lipid peroxidation and changes in the serum fatty acids profile. Full article

The marine environment has a significant impact on life on Earth. Organisms residing in it are vital for the ecosystem but also serve as an inexhaustible source of biologically active compounds. Herein, the biodiversity of two brown seaweeds, Dictyota dichotoma and Dictyota fasciola from the Adriatic Sea, was evaluated. The aim of the study was the determination of differences in compound composition while comparing their activities, including antioxidant, antimicrobial, and enzyme inhibition, in connection to human digestion, dermatology, and neurological disorders. Chemical analysis revealed several terpenoids and steroids as dominant molecules, while fucoxanthin was the main identified pigment in both algae. D. dichotoma had higher protein, carbohydrate, and pigment content. Omega-6 and omega-3 fatty acids were identified, with the highest amount of dihomo-γ-linolenic acid and α-linolenic acid in D. dichotoma. Antimicrobial testing revealed a dose-dependent inhibitory activity of methanolic fraction against Escherichia coli and Staphylococcus aureus. Moderate antioxidant activity was observed for both algae fractions, while the dietary potential was high, especially for the D. fasciola dichloromethane fraction, with inhibition percentages of around 92% for α-amylase and 57% for pancreatic lipase at 0.25 mg/mL. These results suggest that Dictyota species might be a potent source of naturally derived agents for obesity and diabetes. Full article

Dihomo-γ-linolenic acid (DGLA) has emerged as a significant molecule differentiating healthy and inflamed tissues. Its position at a pivotal point of metabolic pathways leading to anti-inflammatory derivatives or via arachidonic acid (ARA) to pro-inflammatory lipid mediators makes this n-6 polyunsaturated fatty acid (PUFA) an intriguing research subject. The balance of ARA to DGLA is probably a critical factor affecting inflammatory processes in the body. The aim of this narrative review was to examine the potential roles of DGLA and related n-6 PUFAs in inflammatory conditions, such as obesity-associated disorders, rheumatoid arthritis, atopic dermatitis, asthma, cancers, and diseases of the gastrointestinal tract. DGLA can be produced by cultured fungi or be obtained via endogenous conversion from γ-linolenic acid (GLA)-rich vegetable oils. Several disease states are characterized by abnormally low DGLA levels in the body, while others can feature elevated levels. A defect in the activity of ∆6-desaturase and/or ∆5-desaturase may be one factor in the initiation and progression of these conditions. The potential of GLA and DGLA administrations as curative or ameliorating therapies in inflammatory conditions and malignancies appears modest at best. Manipulations with ∆6- and ∆5-desaturase inhibitors or combinations of long-chain PUFA supplements with n-3 PUFAs could provide a way to modify the body’s DGLA and ARA production and the concentrations of their pro- and anti-inflammatory mediators. However, clinical data remain scarce and further well-designed studies should be actively promoted. Full article

Antibiotic-resistant strains are a global health-threatening problem. Drug-resistant microbes have compromised the control of infectious diseases. Therefore, the search for a novel class of antibiotic drugs is necessary. Streptomycetes have been described as the richest source of bioactive compounds, including antibiotics. This study was aimed to characterize the antibacterial compounds of Streptomyces sp. PJ85 isolated from dry dipterocarp forest soil in Northeast Thailand. The 16S rRNA gene sequence and phylogenetic analysis showed that PJ85 possessed a high similarity to Streptomyces actinomycinicus RCU-197^T of 98.90%. The PJ85 strain was shown to produce antibacterial compounds that were active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). The active compounds of PJ85 were extracted and purified using silica gel column chromatography. Two active antibacterial compounds, compound 1 and compound PJ85_F39, were purified and characterized with spectroscopy, including liquid chromatography and mass spectrometry (LC–MS). Compound 1 was identified as actinomycin D, and compound PJ85_F39 was identified as dihomo-γ-linolenic acid (DGLA). To the best of our knowledge, this is the first report of the purification and characterization of the antibacterial compounds of S. actinomycinicus. Full article

The zebrafish (Danio rerio) genome contains a single gene fads2 encoding a desaturase (FADS2) with both Δ6 and Δ5 activities, the key player in the endogenous biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), which serve essential functions as membrane components, sources of energy and signaling molecules. LC-PUFAs include the precursors of eicosanoids and are thus predicted to be indispensable molecules for reproductive health in virtually all vertebrates. In mice, an amniotic vertebrate, fads2 deletion mutants, both males and females, have been confirmed to be sterile. In anamniotic vertebrates, such as fish, there is still no information available on the reproductive (in)ability of fads2 mutants, although zebrafish have become an increasingly important model of lipid metabolism, including some aspects of the generation of germ cells and early embryonic development. In the present study, we apply the CRISPR/Cas9 genome editing system to induce mutations in the zebrafish genome and create crispants displaying a degree of fads2 gene editing within the range of 50–80%. Focusing on adult G₀ crispant females, we investigated the LC-PUFA profiles of eggs. Our data suggest an impaired pathway of the LC-PUFA biosynthesis of the ω6 and ω3 series in the first-rate limiting steps of the conversion of linoleic acid (LA) into γ-linolenic acid (GLA), and α-linolenic acid (ALA) into stearidonic acid (SDA), respectively, finally resulting in bad-quality eggs. Our data suggest the existence of an alternative Δ8 pathway, which bypasses the first endogenous LC-PUFA biosynthetic step in zebrafish in vivo, and suggest that the zebrafish bifunctional FADS2 enzyme is actually a trifunctional Δ6/Δ5/Δ8 desaturase. Full article

Cyclooxygenase metabolizes dihomo-γ-linolenic acid and arachidonic acid to form prostaglandin (PG) E, including PGE1 and PGE2, respectively. Although PGE2 is well known to play an important role in the development and maintenance of hyperalgesia and allodynia, the role of PGE1 in pain is unknown. We confirm whether PGE1 induced pain using orofacial pain behavioral test in mice and determine the target molecule of PGE1 in TG neurons with whole-cell patch-clamp and immunohistochemistry. Intradermal injection of PGE1 to the whisker pads of mice induced a reduced threshold, enhancing the excitability of HCN channel-expressing trigeminal ganglion (TG) neurons. The HCN channel-generated inward current (I_h) was increased by 135.3 ± 4.8% at 100 nM of PGE1 in small- or medium-sized TG, and the action of PGE1 on I_h showed a concentration-dependent effect, with a median effective dose (ED₅₀) of 29.3 nM. Adenylyl cyclase inhibitor (MDL12330A), 8-bromo-cAMP, and the EP2 receptor antagonist AH6809 inhibited PGE1-induced I_h. Additionally, PGE1-induced mechanical allodynia was blocked by CsCl and AH6809. PGE1 plays a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons, suggesting a potential therapeutic target in that PGE1 could be involved in pain as endogenous substances under inflammatory conditions. Full article

Sabella spallanzanii and Microcosmus squamiger were profiled for proximate composition, minerals, amino acids, fatty acids (FA), carotenoids, radical scavenging activity on the 2,2-diphenyl-1- picrylhydrazyl (DPPH) radical, oxygen radical absorbance capacity (ORAC) and iron and copper chelating properties. Microcosmus squamiger had the highest level of moisture and crude protein, S. spallanzanii was enriched in crude fat and ash. Both species had similar levels of carbohydrates and energy. There was a prevalence of arginine and glycine in S. spallanzanii, and of taurine in M. squamiger. The most abundant minerals in both species were Na, Ca, and K. The methanol extract of S. spallanzanii had metal chelating properties towards copper and iron, while the methanol extract of M. squamiger was able to chelate copper. M. squamiger extracts had similar ORAC values. Fucoxanthinol and fucoxanthin were the major carotenoids in the M. squamiger dichloromethane extract. Saturated FA were more abundant than unsaturated ones in methanol extracts, and unsaturated FA prevailed in the dichloromethane extracts. Palmitic acid was the predominant FA in methanol extracts, whereas eicosapentaenoic (EPA) and dihomo-γ-linolenic acids were the major compounds in dichloromethane extracts. Low n-6/n-3 ratios were obtained. Our results suggests that both species could be explored as sources of bioactive ingredients with multiple applications. Full article