[Functions and mechanisms of testicular descent in Apodemus agrarius based on transcriptomics and metabolomics].

This study aims to explore the functions and mechanisms of testicular descent in Apodemus agrarius, and analyze the changes in genes and metabolite levels in this process. Illumina NovaSeq and liquid chromatography-mass spectrometry were used for the transcriptomic analysis and metabolomic analysis, respectively, of the normal and descending testis of A. agrarius. Gene ontology (GO) enrichment of the transcriptomic results revealed 240 differentially expressed genes (DEGs), such as Spesp1, Izumo1, Hyal5, and Fabp9. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed 52 DEGs, including Pcyt1, Pla2g4e, Gpd1l, and Lypla3. The qRT-PCR results were consistent with the transcriptomic results in terms of the expression patterns of six randomly selected genes in the normal and descending testis. The metabolomic results revealed 28 differential metabolites associated with the testicular function, including 3-dehydroquinic acid, α-linolenic acid, dihydroxyacetone phosphate, and fructose 1,6-bisphosphate. The conjoint analysis showcased that glycerophospholipid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism may be the key metabolic pathways regulating testicular descent in A. agrarius. This study will help to understand the mechanism of testicular descent and lay a theoretical foundation for exploring the mechanisms of the population changes of A. agrarius and developing laboratory animal resources.

Comprehensive Analysis of Biomass from Chlorella sorokiniana Cultivated with Industrial Flue Gas as the Carbon Source.

Chlorella sorokiniana, isolated from a pond adjacent to a cement plant, was cultured using flue gas collected directly from kiln emissions using 20 L and 25000 L photobioreactors. Lipids, proteins, and polysaccharides were analyzed to understand their overall composition for potential applications. The lipid content ranged from 17.97% to 21.54% of the dry biomass, with carotenoid concentrations between 8.4 and 9.2 mg/g. Lutein accounted for 55% of the total carotenoids. LC/MS analysis led to the identification of 71 intact triacylglycerols, 8 lysophosphatidylcholines, 10 phosphatidylcholines, 9 monogalactosyldiacylglycerols, 12 digalactosyldiacylglycerols, and 1 sulfoquinovosyl diacylglycerol. Palmitic acid, oleic acid, linoleic acid, and α-linolenic acid were the main fatty acids. Polyunsaturated fatty acid covers ≥ 56% of total fatty acids. Protein isolates and polysaccharides were also extracted. Protein purity was determined to be ≥75% by amino acid analysis, with all essential amino acids present. Monomer analysis of polysaccharides suggested that they are composed of mainly D-(+)-mannose, D-(+)-galactose, and D-(+)-glucose. The results demonstrate that there is no adverse effect on the metabolite profile of C. sorokiniana biomass cultured using flue gas as the primary carbon source, revealing the possibility of utilizing such algal biomass in industrial applications such as animal feed, sources of cosmeceuticals, and as biofuel.

α-Linolenic Acid Vesicles-Mediated Tau Internalization in Microglia.

In Alzheimer's disease, the synaptic loss is prominent due to the accumulation of Amyloid ßeta (Aß) protein in synapses, which affect neurotransmission, and thus ultimately causes neuronal loss. Tau, a microtubule-associated protein, is a vital protein of intracellular neurofibrillary tangles (NFTs) in AD. Along with the accumulation of aberrant proteins, glial cells, mainly astrocytes and microglia, play a major role in impairing neuronal network. Microglia have the ability to phagocytose Tau and rerelease in exosomes, which causes further spreading of Tau. Reduction in exosome synthesis can reduce spreading of Tau. Modulating microglia to clear the extracellular Tau seeds by its imported degradation would resolve the disease condition in Alzheimer's disease. In this study, we have shown the ability of α-linolenic acid (ALA) to inhibit the Tau aggregation and modulate their internalization property in microglial cells.

Sex-dependent differences in tissue and blood n-3 PUFA levels following ALA or ALA + DHA feeding of liver-specific Elovl2-KO and control mice.

Docosahexaenoic acid (DHA, 22:6n-3) must be consumed from the diet or synthesized from polyunsaturated fatty acid (PUFA) precursors, such as α-linolenic acid (ALA, 18:3n-3). Elongase 2 (encoded by Elovl2 gene) catalyzes two elongation reactions in the PUFA biosynthesis pathway and may be important in regulating the observed sex differences in n-3 PUFA levels. Our aim was to determine how targeted knockout of liver Elovl2 affects tissue and blood n-3 PUFA levels in male and female C57BL/6J mice. Twenty-eight-day old male and female liver Elovl2-KO and control mice were placed onto one of two dietary protocols for a total of 8 weeks (4-8 mice per genotype, per diet, per sex): 1) an 8-week 2 % ALA in total fat diet or 2) a 4-week 2 % ALA diet followed by a 4-week 2 % ALA + 2 % DHA diet. Following this 8-week feeding period, 12-week-old mice were sacrificed and serum, red blood cells (RBC), liver, heart and brain were collected and fatty acid levels measured. Significant interaction effects (p < 0.05, sex x genotype) for serum, RBC, liver and heart DHA levels were identified. In serum and liver, DHA levels were significantly different (p < 0.01) between all groups with male controls > female controls > female KO > male KO in serum and female controls > male controls > female KO > male KO in liver. In RBCs and the heart, female controls = male controls > female KO > male KO (p < 0.001). The addition of DHA to diet removed the interaction effects on DHA levels in the serum, liver and heart, yielding a significant sex effect in serum, liver (female > male, p < 0.01) and brain (male > female, p < 0.05) and genotype effect in serum and heart (control > KO, p < 0.05). Ablation of liver Elovl2 results in significantly lower blood and tissue DHA in a sex-dependent manner, suggesting a role for Elovl2 on sex differences in n-3 PUFA levels.

Integrated Transcriptomic and Metabolomic Analysis Reveal the Dynamic Process of Bama Hemp Seed Development and the Accumulation Mechanism of α-Linolenic Acid and Linoleic Acid.

Bama County is a world-famous longevity county in the Guangxi Province, China. Bama hemp is a traditional seed used in hemp cultivation in the Bama County. The seeds contain abundant unsaturated fatty acids, particularly linoleic acid (LA) and linolenic acid in the golden ratio. These two substances have been proven to be related to human health and the prevention of various diseases. However, the seed development and seed oil accumulation mechanisms remain unclear. This study employed a combined analysis of physiological, transcriptomic, and metabolomic parameters to elucidate the fatty acid formation patterns in Bama hemp seeds throughout development. We found that seed oil accumulated at a late stage in embryo development, with seed oil accumulation following an "S″-shaped growth curve, and positively correlated with seed size, sugar content, protein content, and starch content. Transcriptome analysis identified genes related to the metabolism of LA, α-linolenic acid (ALA), and jasmonic acid (JA). We found that the FAD2 gene was upregulated 165.26 folds and the FAD3 gene was downregulated 6.15 folds at day 21. Metabolomic changes in LA, ALA, and JA compounds suggested a competitive relationship among these substances. Our findings indicate that the peak period of substance accumulation and nutrient accumulation in Bama hemp seeds occurs during the midstage of seed development (day 21) rather than in the late stage (day 40). The results of this research will provide a theoretical basis for local cultivation and deep processing of Bama hemp.

Dietary combination of linseed and hazelnut skin as a sustainable strategy to enrich lamb with health promoting fatty acids.

This study investigated the effect of the inclusion of extruded linseed and hazelnut skin on fatty acid (FA) metabolism in finishing lambs. Forty lambs were divided into 4 groups and fed for 60 d with: a conventional cereal-based diet, or the same diet with 8% of extruded linseed, or 15% of hazelnut skin, or 4% of linseed plus 7.5% of hazelnut skin as partial replacement of maize. Dietary treatments did not affect growth performances, carcass traits, and ruminal fermentation. The combined effect of linseed and hazelnut skin enriched the intramuscular fat with health promoting FA. Particularly, increases in α-linolenic acid (3.75-fold), and very long-chain n-3 poly-unsaturated FA (+ 40%) were attributed to the supplementation with linseed, rich in α-linolenic acid. In addition, increases in rumenic (+ 33%), and vaccenic (+ 59%) acids were attributed to hazelnut skin tannins modulating ruminal biohydrogenation and accumulating intermediate metabolites. The simultaneous inclusion of linseed and hazelnut skin can be a profitable strategy for enriching the intramuscular fat of lambs with health promoting FA, without adverse effects on ruminal fermentation and animal performance.

Current Insights into the Effects of Dietary α-Linolenic Acid Focusing on Alterations of Polyunsaturated Fatty Acid Profiles in Metabolic Syndrome.

The plant-derived α-linolenic acid (ALA) is an essential n-3 acid highly susceptible to oxidation, present in oils of flaxseeds, walnuts, canola, perilla, soy, and chia. After ingestion, it can be incorporated in to body lipid pools (particularly triglycerides and phospholipid membranes), and then endogenously metabolized through desaturation, elongation, and peroxisome oxidation to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with a very limited efficiency (particularly for DHA), beta-oxidized as an energy source, or directly metabolized to C18-oxilipins. At this moment, data in the literature about the effects of ALA supplementation on metabolic syndrome (MetS) in humans are inconsistent, indicating no effects or some positive effects on all MetS components (abdominal obesity, dyslipidemia, impaired insulin sensitivity and glucoregulation, blood pressure, and liver steatosis). The major effects of ALA on MetS seem to be through its conversion to more potent EPA and DHA, the impact on the n-3/n-6 ratio, and the consecutive effects on the formation of oxylipins and endocannabinoids, inflammation, insulin sensitivity, and insulin secretion, as well as adipocyte and hepatocytes function. It is important to distinguish the direct effects of ALA from the effects of EPA and DHA metabolites. This review summarizes the most recent findings on this topic and discusses the possible mechanisms.

The balance of n-6 and n-3 fatty acids in canine, feline, and equine nutrition: exploring sources and the significance of alpha-linolenic acid.

Both n-6 and n-3 fatty acids (FA) have numerous significant physiological roles for mammals. The interplay between these families of FA is of interest in companion animal nutrition due to the influence of the n-6:n-3 FA ratio on the modulation of the inflammatory response in disease management and treatment. As both human and animal diets have shifted to greater consumption of vegetable oils rich in n-6 FA, the supplementation of n-3 FA to canine, feline, and equine diets has been advocated for. Although fish oils are commonly added to supply the long-chain n-3 FA eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), a heavy reliance on this ingredient by the human, pet food, and equine supplement industries is not environmentally sustainable. Instead, sustainable sourcing of plant-based oils rich in n-3 α-linolenic acid (ALA), such as flaxseed and camelina oils, emerges as a viable option to support an optimal n-6:n-3 FA ratio. Moreover, ALA may offer health benefits that extend beyond its role as a precursor for endogenous EPA and DHA production. The following review underlines the metabolism and recommendations of n-6 and n-3 FA for dogs, cats, and horses and the ratio between them in promoting optimal health and inflammation management. Additionally, insights into both marine and plant-based n-3 FA sources will be discussed, along with the commercial practicality of using plant oils rich in ALA for the provision of n-3 FA to companion animals.

In the realm of companion animal nutrition, the balance between the n-6 and n-3 fatty acids (FA) is important. The shared metabolic pathway of these two FA families and the respective signaling molecules produced have implications for the well-being of companion animals such as dogs, cats, and even horses. The n-6:n-3 FA ratio of the diet can directly influence inflammatory responses, disease management, and overall health. Given the prevalent use of n-6 FA-rich vegetable oils in both human and animal diets, there is a growing need to supplement these animals' diets with n-3 FA. While fish oils containing the long-chain n-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been the conventional choice, their overreliance is environmentally unsustainable. Plant-based oils abundant in the n-3 FA α-linolenic acid (ALA) such as flaxseed and camelina oils should be considered, especially given the health benefits of ALA that extend beyond its role as a precursor to EPA and DHA. This review examines the importance of n-3 FA and the n-6:n-3 FA ratio in companion animal diets on animal health while discussing environmentally sustainable alternatives to fish oil to supplement n-3 FA.

Dietary docosahexaenoic acid (DHA) downregulates liver DHA synthesis by inhibiting eicosapentaenoic acid elongation.

DHA is abundant in the brain where it regulates cell survival, neurogenesis, and neuroinflammation. DHA can be obtained from the diet or synthesized from alpha-linolenic acid (ALA; 18:3n-3) via a series of desaturation and elongation reactions occurring in the liver. Tracer studies suggest that dietary DHA can downregulate its own synthesis, but the mechanism remains undetermined and is the primary objective of this manuscript. First, we show by tracing 13C content (δ13C) of DHA via compound-specific isotope analysis, that following low dietary DHA, the brain receives DHA synthesized from ALA. We then show that dietary DHA increases mouse liver and serum EPA, which is dependant on ALA. Furthermore, by compound-specific isotope analysis we demonstrate that the source of increased EPA is slowed EPA metabolism, not increased DHA retroconversion as previously assumed. DHA feeding alone or with ALA lowered liver elongation of very long chain (ELOVL2, EPA elongation) enzyme activity despite no change in protein content. To further evaluate the role of ELOVL2, a liver-specific Elovl2 KO was generated showing that DHA feeding in the presence or absence of a functional liver ELOVL2 yields similar results. An enzyme competition assay for EPA elongation suggests both uncompetitive and noncompetitive inhibition by DHA depending on DHA levels. To translate our findings, we show that DHA supplementation in men and women increases EPA levels in a manner dependent on a SNP (rs953413) in the ELOVL2 gene. In conclusion, we identify a novel feedback inhibition pathway where dietary DHA downregulates its liver synthesis by inhibiting EPA elongation.

Arabidopsis seeds altered in the circadian clock protein TOC1 are characterized by higher level of linolenic acid.

The circadian clock plays a critical role in regulating plant physiology and metabolism. However, the way in which the clock impacts the regulation of lipid biosynthesis in seeds is partially understood. In the present study, we characterized the seed fatty acid (FA) and glycerolipid (GL) compositions of pseudo-response regulator mutants. Among these mutants, toc1 (timing of cab expression 1) exhibited the most significant differences compared to control plants. These included an increase in total FA content, characterized by elevated levels of linolenic acid (18:3) along with a reduction in linoleic acid (18:2). Furthermore, our findings revealed that toc1 developing seeds showed increased expression of genes related to FA metabolism. Our results show a connection between TOC1 and lipid metabolism in Arabidopsis seeds.

Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid.

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate; however, the molecular mechanisms underpinning its pathogenesis are not well elucidated. Here, a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus (SGIV), focusing on the roles of key metabolites. Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver. Furthermore, SGIV significantly reduced the contents of lipid droplets, triglycerides, cholesterol, and lipoproteins. Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways, with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid (ALA), consistent with disturbed lipid homeostasis in the liver. Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide, carbohydrate, amino acid, and lipid metabolism, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid (LA) metabolites, and the accumulation of L-glutamic acid (GA), accompanied by alterations in immune, inflammation, and cell death-related genes. Further experimental data showed that ALA, but not GA, suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host. Collectively, these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

Impact of changes in root biomass on the occurrence of internal browning in radish root.

The purpose of this study was to investigate the effects of root biomass during the later stage of growth on fatty acid composition and lipid peroxidation, and to clarify the physiological mechanisms by which these differences affect internal browning (IB) development in radish roots. Therefore, we controlled the enlargement of roots by changing the thinning period and generated plots composed of roots with different biomass in the latter half of growth. The earlier the radish seedlings were thinned, the more vigorous the root growth from an earlier stage was achieved. Earlier thinning caused IB from the early stage of root maturation, and IB severity progressed with subsequent age progression; however, IB damage did not occur when root size during the later growth stage was kept small by later thinning. Higher levels of hydrogen peroxide, peroxidase activity, NADPH-dependent reactive oxygen species (ROS) burst-related genes, and carbonyl compounds were detected in earlier-thinned large-sized roots compared to later-thinned small-sized ones. Compared with the latter small-sized roots, the former large-sized roots had a lower ratio of linoleic acid (18:2) and a higher ratio of α-linolenic acid (α-18:3). Furthermore, in earlier-thinned large-sized roots, higher levels of phospholipase- and/or lipoxygenase-related genes were detected compared to later-thinned small-sized ones. These facts suggest the possibility that root biomass in the later stage of growth affects the desaturation of membrane fatty acids, ROS concentration, and activity of fatty acid degrading enzymes, and controls the occurrence of IB injury through membrane oxidative degradation.

Biochemical and Biophysical Characterization of Tau and α-Linolenic Acid Vesicles In Vitro.

Alzheimer's disease (AD) is characterized by the abnormal accumulation of disordered protein, that is, extracellular senile plaques of amyloid-ß (Aß) and intracellular neurofibrillary tangles of Tau. Tau protein has gained the attention in recent years owing to the ability to propagate in a "prion-like" nature. The disordered protein Tau possesses a high positive charge, which allows its binding to anionic proteins and factors. The native disorder of proteins attends the ß-sheet structure from its random-coiled conformation upon charge compensation by various polyanionic agents such as heparin, RNA, etc. Anionic lipids such as arachidonic acid (AA) and oleic acid (OA) are also one of the factors which can induce aggregation of Tau in physiological conditions. The free units of Tau protein can bind to lipid membranes through its repeat domain (RD), the anionic side chains of the membrane lipids induce aggregation of Tau by reducing the activation barrier. In this study, we investigated the role of α-linolenic acid (ALA) as an inducing agent for Tau aggregation in vitro conditions. Omega-3 fatty acids bear a capacity to reduce the pathology of Tau by downregulating the Tau phosphorylation pathway. We have studied by using various biochemical or biophysical methods the potency of ALA as an aggregating agent for Tau. We have implemented different techniques such as SDS-PAGE, transmission electron microscopy, CD spectroscopy to evaluated higher-order aggregates of Tau upon induction by ALA.

α-Linolenic Acid Induces Microglial Activation and Extracellular Tau Internalization.

Neuroinflammation is the brain condition that occurs due to the hyper-activation of brain's immune cells and microglia, over the stimulation of extracellular aggregated proteins such as amyloid plaques and by extracellular Tau as well. The phenotypic changes of microglia from inflammatory to anti-inflammatory can be triggered by many factors, which also includes dietary fatty acids. The classes of omega-3 fatty acids are the majorly responsible in maintaining the anti-inflammatory phenotype of microglia. The enhanced phagocytic ability of microglia might induce the clearance of extracellular aggregated proteins, such as amyloid beta and Tau. In this study, we emphasized on the effect of α-linolenic acid (ALA) on the activation of microglia and internalization of the extracellular Tau seed in microglia.

Cotton BLH1 and KNOX6 antagonistically modulate fiber elongation via regulation of linolenic acid biosynthesis.

BEL1-LIKE HOMEODOMAIN (BLH) proteins are known to function in various plant developmental processes. However, the role of BLHs in regulating plant cell elongation is still unknown. Here, we identify a BLH gene, GhBLH1, that positively regulates fiber cell elongation. Combined transcriptomic and biochemical analyses reveal that GhBLH1 enhances linolenic acid accumulation to promote cotton fiber cell elongation by activating the transcription of GhFAD7A-1 via binding of the POX domain of GhBLH1 to the TGGA cis-element in the GhFAD7A-1 promoter. Knockout of GhFAD7A-1 in cotton significantly reduces fiber length, whereas overexpression of GhFAD7A-1 results in longer fibers. The K2 domain of GhKNOX6 directly interacts with the POX domain of GhBLH1 to form a functional heterodimer, which interferes with the transcriptional activation of GhFAD7A-1 via the POX domain of GhBLH1. Overexpression of GhKNOX6 leads to a significant reduction in cotton fiber length, whereas knockout of GhKNOX6 results in longer cotton fibers. An examination of the hybrid progeny of GhBLH1 and GhKNOX6 transgenic cotton lines provides evidence that GhKNOX6 negatively regulates GhBLH1-mediated cotton fiber elongation. Our results show that the interplay between GhBLH1 and GhKNOX6 modulates regulation of linolenic acid synthesis and thus contributes to plant cell elongation.

Internalization and Endosomal Trafficking of Extracellular Tau in Microglia Improved by α-Linolenic Acid.

Alzheimer's disease (AD) is distinguished by extracellular accumulation of amyloid-beta plaques and intracellular neurofibrillary tangles of Tau. Pathogenic Tau species are also known to display "prion-like propagation," which explains their presence in extracellular spaces as well. Glial population, especially microglia, tend to proclaim neuroinflammatory condition, disrupted signaling mechanisms, and cytoskeleton deregulation in AD. Omega-3 fatty acids play a neuroprotective role in the brain, which can trigger the anti-inflammatory pathways as well as actin dynamics in the cells. Improvement of cytoskeletal assembly mechanism by omega-3 fatty acids would regulate the other signaling cascades in the cells, leading to refining clearance of extracellular protein burden in AD. In this study, we focused on analyzing the ability of α-linolenic acid (ALA) as a regulator of actin dynamics to balance the signaling pathways in microglia, including endocytosis of extracellular Tau burden in AD.

The tree peony DREB transcription factor PrDREB2D regulates seed α-linolenic acid accumulation.

α-Linolenic acid (ALA), an essential fatty acid (FA) for human health, serves as the precursor of 2 nutritional benefits, docosahexaenoic acid and eicosapentaenoic acid, and can only be obtained from plant foods. We previously found that phospholipid:diacylglycerol acyltransferase 2 (PrPDAT2) derived from ALA-rich tree peony (Paeonia rockii) can promote seed ALA accumulation. However, the regulatory mechanism underlying its promoting effect on ALA accumulation remains unknown. Here, we revealed a tree peony dehydration-responsive element binding transcription factor, PrDREB2D, as an upstream regulator of PrPDAT2, which is involved in regulating seed ALA accumulation. Our findings demonstrated that PrDREB2D serves as a nucleus-localized transcriptional activator that directly activates PrPDAT2 expression. PrDREB2D altered the FA composition in transient overexpression Nicotiana benthamiana leaves and stable transgenic Arabidopsis (Arabidopsis thaliana) seeds. Repressing PrDREB2D expression in P. rockii resulted in decreased PrPDAT2 expression and ALA accumulation. In addition, PrDREB2D strengthened its regulation of ALA accumulation by recruiting the cofactor ABA-response element binding factor PrABF2b. Collectively, the study findings provide insights into the mechanism of seed ALA accumulation and avenues for enhancing ALA yield via biotechnological manipulation.

Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia.

Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia accompanied by memory loss and depression. The direct pathways and specific mechanisms in the central nervous system (CNS) for addressing fatty acid imbalances in MetS have not yet been fully elucidated. Among polyunsaturated acids, linoleic acid (LA, n6-PUFA) and α-linolenic acid (ALA, n3-PUFA), which are two essential fatty acids that should be provided by food sources (e.g., vegetable oils and seeds), have been reported to regulate various cellular mechanisms including apoptosis, inflammatory responses, mitochondrial biogenesis, and insulin signaling. Furthermore, inadequate intake of LA and ALA is reported to be involved in neuropathology and neuropsychiatric diseases as well as imbalanced metabolic conditions. Herein, we review the roles of LA and ALA on metabolic-related dementia focusing on insulin resistance, dyslipidemia, synaptic plasticity, cognitive function, and neuropsychiatric issues. This review suggests that LA and ALA are important fatty acids for concurrent treatment of both MetS and neurological problems.

Alpha-linolenic acid protects against methotrexate-induced nephrotoxicity in mouse kidney cells.

OBJECTIVE: Methotrexate (MTX) is a folic acid antagonist used in chronic inflammatory diseases and various cancer treatments. Although the main mechanism of the toxic effect of MTX is not known, it is stated that it causes oxidative stress and inflammation. Alpha-linolenic acid (ALA) protects against oxidative stress, apoptosis, and inflammation. For this reason, we aimed to find out the useful effect of ALA on MTX-induced nephrotoxicity MATERIALS AND METHODS: The mice were divided into 4 groups randomly. The control group was treated with physiological saline solution; the ALA group was treated with ALA (200 mg/kg) by gavage; MTX-treated group received 20 mg/kg i.p. (intraperitoneal) MTX; and MTX+ALA treated group received 20 mg/kg i.p. MTX and ALA 200 mg/kg by gavage. All of the drugs were performed once a day for 9 days. RESULTS: Alpha-linolenic acid significantly decreased oxidative stress parameters and MTX-induced inflammatory and apoptotic mediators. Furthermore, histopathological examination showed that MTX induced significant edematous damage, and ALA treatment attenuated this damage in renal tissue. CONCLUSIONS: Our results revealed that ALA may be helpful against MTX-induced nephrotoxicity in mice via its antioxidant and anti-inflammatory properties.

The Effects of a Low Linoleic Acid/α-Linolenic Acid Ratio on Lipid Metabolism and Endogenous Fatty Acid Distribution in Obese Mice.

A reduced risk of obesity and metabolic syndrome has been observed in individuals with a low intake ratio of linoleic acid/α-linolenic acid (LA/ALA). However, the influence of a low ratio of LA/ALA intake on lipid metabolism and endogenous fatty acid distribution in obese patients remains elusive. In this investigation, 8-week-old C57BL/6J mice were randomly assigned to four groups: low-fat diet (LFD) as a control, high-fat diet (HFD), high-fat diet with a low LA/ALA ratio (HFD+H3L6), and high-fat diet with a high LA/ALA ratio (HFD+L3H6) for 16 weeks. Our results show that the HFD+H3L6 diet significantly decreased the liver index of HFD mice by 3.51%, as well as the levels of triacylglycerols (TGs) and low-density lipoprotein cholesterol (LDL-C) by 15.67% and 10.02%, respectively. Moreover, the HFD+H3L6 diet reduced the pro-inflammatory cytokines interleukin-6 (IL-6) level and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and elevated the level of superoxide dismutase (SOD) in the liver. The HFD+H3L6 diet also resulted in the downregulation of fatty acid synthetase (FAS) and sterol regulatory element binding proteins-1c (SREBP-1c) expression and the upregulation of peroxisome proliferator-activated receptor-α (PPAR-α) and acyl-CoA oxidase 1 (ACOX1) gene expression in the liver. The low LA/ALA ratio diet led to a notable increase in the levels of ALA and its downstream derivative docosahexaenoic acid (DHA) in the erythrocyte, liver, perienteric fat, epididymal fat, perirenal fat, spleen, brain, heart, and gastrocnemius, with a strong positive correlation. Conversely, the accumulation of LA in abdominal fat was more prominent, and a high LA/ALA ratio diet exacerbated the deposition effect of LA. In conclusion, the low LA/ALA ratio not only regulated endogenous fatty acid levels but also upregulated PPAR-α and ACOX1 and downregulated SREBP-1c and FAS gene expression levels, thus maintaining lipid homeostasis. Optimizing dietary fat intake is important in studying lipid nutrition. These research findings emphasize the significance of understanding and optimizing dietary fat intake.