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International Journal of Molecular... Jul 2023A 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...
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 () and sterol regulatory element binding proteins-1c () expression and the upregulation of peroxisome proliferator-activated receptor-α () and acyl-CoA oxidase 1 () 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 and and downregulated and 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.
Topics: Mice; Animals; Fatty Acids; Lipid Metabolism; alpha-Linolenic Acid; Linoleic Acid; Mice, Obese; Peroxisome Proliferator-Activated Receptors; Sterol Regulatory Element Binding Protein 1; Mice, Inbred C57BL; Liver; Diet, High-Fat; Obesity
PubMed: 37569494
DOI: 10.3390/ijms241512117 -
Diabetes Jan 2024In contrast to the well-defined biological feedback loops controlling glucose, the mechanisms by which the body responds to changes in fatty acid availability are less...
UNLABELLED
In contrast to the well-defined biological feedback loops controlling glucose, the mechanisms by which the body responds to changes in fatty acid availability are less clearly defined. Growth differentiating factor 15 (GDF15) suppresses the consumption of diets high in fat but is paradoxically increased in obese mice fed a high-fat diet. Given this interrelationship, we investigated whether diets high in fat could directly increase GDF15 independently of obesity. We found that fatty acids increase GDF15 levels dose dependently, with the greatest response observed with linolenic acid. GDF15 mRNA expression was modestly increased in the gastrointestinal tract; however, kidney GDF15 mRNA was ∼1,000-fold higher and was increased by more than threefold, with subsequent RNAscope analysis showing elevated expression within the cortex and outer medulla. Treatment of wild-type mice with linolenic acid reduced food intake and body mass; however, this effect disappeared in mice lacking the GDF15 receptor GFRAL. An equal caloric load of glucose did not suppress food intake or reduce body mass in either wild-type or GFRAL-knockout mice. These data indicate that fatty acids such as linolenic acid increase GDF15 and suppress food intake through a mechanism requiring GFRAL. These data suggest that a primary physiological function of GDF15 may be as a fatty acid sensor designed to protect cells from fatty acid overload.
ARTICLE HIGHLIGHTS
The mechanisms by which the body responds to changes in fatty acid availability are less clearly defined. We investigated whether diets high in fat could directly increase growth differentiating factor 15 (GDF15) independently of obesity. Fatty acids increase GDF15 and reduce food intake through a GFRAL signaling axis. GDF15 is a sensor of fatty acids that may have important implications for explaining increased satiety after consumption of diets high in fat.
Topics: Animals; Mice; Eating; Fatty Acids; Glucose; Linolenic Acids; Mice, Knockout; Obesity; RNA, Messenger
PubMed: 37847913
DOI: 10.2337/db23-0495 -
European Review For Medical and... Nov 2023Methotrexate (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...
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.
Topics: Mice; Animals; Methotrexate; alpha-Linolenic Acid; Antioxidants; Oxidative Stress; Inflammation; Kidney
PubMed: 38039041
DOI: 10.26355/eurrev_202311_34479 -
Expert Review of Neurotherapeutics Mar 2024Targeted interventions are needed to delay or prevent the onset of neurodegenerative diseases. Poor dietary habits are associated with cognitive decline, highlighting... (Review)
Review
INTRODUCTION
Targeted interventions are needed to delay or prevent the onset of neurodegenerative diseases. Poor dietary habits are associated with cognitive decline, highlighting the benefits of a healthy diet with fish and polyunsaturated fatty acids (PUFAs). Intake of omega-3 PUFAs docosahexaenoic acid (DHA), α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) is linked with healthy aging, cardiovascular benefits, and reduced risk of Alzheimer's disease. Although omega-3 has health benefits, its intake is often inadequate and insufficient in modern diets. Although fish oil supplements offer an alternative source, inconsistent results from clinical trials raise questions about the factors determining their success.
AREAS COVERED
In this this review, the authors discuss the aforementioned determining factors and highlight strategies that could enhance the effectiveness of omega-3 PUFAs interventions for dementia and cognitive decline. Moreover, the authors provide suggestions for potential future research.
EXPERT OPINION
Factors such as diet, lifestyle, and genetic predisposition can all influence the effectiveness of omega-3 supplementation. When implementing clinical trials, it is crucial to consider these factors and recognize their potential impact on the interpretation of results. It is important to study each variable independently and the interactions between them.
Topics: Humans; Fatty Acids, Omega-3; Eicosapentaenoic Acid; Docosahexaenoic Acids; Dietary Supplements; Dementia
PubMed: 38379273
DOI: 10.1080/14737175.2024.2313547 -
Journal of Traditional Chinese Medicine... Oct 2023To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome (CFS) and explore the effects on gut microbiota and metabolic profiles.
OBJECTIVE
To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome (CFS) and explore the effects on gut microbiota and metabolic profiles.
METHODS
Forty-eight male Sprague-Dawley rats were randomly assigned to control group (Con), CFS model group (Mod, established by multiple chronic stress for 35 d), MoxA group (CFS model with moxibustion Shenque (CV8) and Guanyuan (CV4), 10 min/d, 28 d) and MoxB group (CFS model with moxibustion Zusanli (ST36), 10 min/d, 28 d). Open-field test (OFT) and Morris-water-maze test (MWMT) were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer (LC-MS) based fecal metabolomics were executed, as well as Spearman correlation analysis, was utilized to uncover the functional relevance between the potential metabolites and gut microbiota.
RESULTS
The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT. Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition, including increases in pro-inflammatory species (such as Proteobacteria) and decreases in anti-inflammatory species (such as Bacteroides, Lactobacillus, Ruminococcus, and Prevotella). Moxibustion partially normalized these changes in the gut microbiota. Furthermore, CFS was associated with metabolic disorders, which were effectively ameliorated by moxibustion. This was demonstrated by the normalization of 33 microbiota-related metabolites, including mannose ( 0.001), aspartic acid ( 0.009), alanine ( 0.007), serine ( 0.000), threonine ( 0.027), methionine ( 0.023), 5-hydroxytryptamine ( 0.008), alpha-linolenic acid ( 0.003), eicosapentaenoic acid ( 0.006), hypoxanthine ( 0.000), vitamin B6 ( 0.000), cholic acid ( 0.013), and taurocholate ( 0.002). Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels, with a notable negative relationship between LCA and Bacteroides.
CONCLUSIONS
In this study, we demonstrated that moxibustion has an antifatigue-like effect. The results from the 16S rRNA gene sequencing and metabolomics analysis suggest that the therapeutic effects of moxibustion on CFS are related to the regulation of gut microorganisms and their metabolites. The increase in Bacteroides and decrease in LCA may be key targets for the moxibustion treatment of CFS.
Topics: Rats; Male; Animals; Gastrointestinal Microbiome; Rats, Sprague-Dawley; Moxibustion; Fatigue Syndrome, Chronic; RNA, Ribosomal, 16S; Metabolomics
PubMed: 37946480
DOI: 10.19852/j.cnki.jtcm.20231018.004 -
Metabolites Dec 2023A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase in saturated fatty acids in the membrane. The homolog of...
A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase in saturated fatty acids in the membrane. The homolog of stearoyl-CoA desaturase, FAT-7, introduces the first double bond into saturated C18 fatty acids yielding oleic acid, and is a critical regulatory point for surviving cold and glucose stress. Here, we incorporated C stable isotopes into the diet of nematodes and quantified the C-labelled fatty acid using GC-MS and HPLC/MS-MS to track its metabolic response to various concentrations of glucose. Previous work has analyzed the membrane composition of when responding to mild glucose stress and showed few alterations in the overall fatty acid composition in the membrane. Here, in nematodes exposed to higher concentrations of glucose, a specific reduction in oleic acid and linoleic acid was observed. Using time courses and stable isotope tracing, the response of fatty acid metabolism to increasing levels of glucose stress is characterized, revealing the funneling of monounsaturated fatty acids to preserve the abundance of polyunsaturated fatty acids. Taken together, higher levels of glucose unveil a specific reduction in oleic and linolenic acid in the metabolic rewiring required to survive glucose stress.
PubMed: 38132867
DOI: 10.3390/metabo13121185 -
Foods (Basel, Switzerland) Nov 2023This study analyzed and evaluated the basic crude fat contents, crude protein contents, phenolic compounds, lipid compositions (fatty acids, phytosterols, and...
This study analyzed and evaluated the basic crude fat contents, crude protein contents, phenolic compounds, lipid compositions (fatty acids, phytosterols, and tocopherols), and amino acid compositions of 26 walnut samples from 11 walnut-growing provinces in China. The results indicate that the oil contents of the samples varied from 60.08% to 71.06%, and their protein contents ranged from 7.26 g/100 g to 19.50 g/100 g. The composition of fatty acids corresponded to palmitic acid at 4.61-8.27%, stearic acid at 1.90-3.55%, oleic acid at 15.50-32.28%, linoleic acid at 53.44-67.64%, and α-linolenic acid at 2.45-12.77%. The samples provided micronutrients in widely varying amounts, including tocopherol, phytosterol, and total phenolic content, which were found in the walnut oil samples in amounts ranging from 356.49 to 930.43 mg/kg, from 1248.61 to 2155.24 mg/kg, and from 15.85 to 68.51 mg/kg, respectively. A comprehensive evaluation of walnut oil quality in the samples from the 11 provinces using a principal component analysis was conducted. The findings revealed that the samples from Henan, Gansu, and Zhejiang had the highest composite scores among all provinces. Overall, Yunnan-produced walnuts had high levels of crude fat, polyunsaturated fatty acids, and total tocopherols, making them more suitable for producing high-quality oil, whereas Henan-produced walnuts, although lower in crude fat, had a higher crude protein content and composite score, thus showing the best walnut characteristics.
PubMed: 38002181
DOI: 10.3390/foods12224123 -
Molecular Neurobiology Aug 2023Hair is a noninvasive valuable biospecimen for the long-term assessment of endogenous metabolic disturbance. Whether the hair is suitable for identifying biomarkers of...
Rat Hair Metabolomics Analysis Reveals Perturbations of Unsaturated Fatty Acid Biosynthesis, Phenylalanine, and Arachidonic Acid Metabolism Pathways Are Associated with Amyloid-β-Induced Cognitive Deficits.
Hair is a noninvasive valuable biospecimen for the long-term assessment of endogenous metabolic disturbance. Whether the hair is suitable for identifying biomarkers of the Alzheimer's disease (AD) process remains unknown. We aim to investigate the metabolism changes in hair after β-amyloid (Aβ) exposure in rats using ultra-high-performance liquid chromatography-high-resolution mass spectrometry-based untargeted and targeted methods. Thirty-five days after Aβ induction, rats displayed significant cognitive deficits, and forty metabolites were changed, of which twenty belonged to three perturbed pathways: (1) phenylalanine metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis-L-phenylalanine, phenylpyruvate, ortho-hydroxyphenylacetic acid, and phenyllactic acid are up-regulated; (2) arachidonic acid (ARA) metabolism-leukotriene B4 (LTB4), arachidonyl carnitine, and 5(S)-HPETE are upregulation, but ARA, 14,15-DiHETrE, 5(S)-HETE, and PGB2 are opposite; and (3) unsaturated fatty acid biosynthesis- eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), FA 18:3 + 1O, and FA 18:3 + 2O are downregulated. Linoleic acid metabolism belonging to the biosynthesis of unsaturated fatty acid includes the upregulation of 8-hydroxy-9,10-epoxystearic acid, 13-oxoODE, and FA 18:2 + 4O, and downregulation of 9(S)-HPODE and dihomo-γ-linolenic acid. In addition, cortisone and dehydroepiandrosterone belonging to steroid hormone biosynthesis are upregulated. These three perturbed metabolic pathways also correlate with cognitive impairment after Aβ stimulation. Furthermore, ARA, DHA, EPA, L-phenylalanine, and cortisone have been previously implicated in the cerebrospinal fluid of AD patients and show a similar changing trend in Aβ rats' hair. These data suggest hair can be a useful biospecimen that well reflects the expression of non-polar molecules under Aβ stimulation, and the five metabolites have the potential to serve as novel AD biomarkers.
Topics: Animals; Rats; Arachidonic Acid; Phenylalanine; Cortisone; Fatty Acids, Unsaturated; Amyloid beta-Peptides; Metabolomics; Cognitive Dysfunction; Alzheimer Disease; Cognition; Hair; Biomarkers
PubMed: 37095368
DOI: 10.1007/s12035-023-03343-6 -
Zoological Research May 2024Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate; however, the molecular mechanisms underpinning its pathogenesis are not well...
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.
Topics: Animals; alpha-Linolenic Acid; Fish Diseases; Liver; Iridovirus; DNA Virus Infections; Metabolomics; Antiviral Agents; Transcriptome; Metabolic Reprogramming; Multiomics
PubMed: 38682434
DOI: 10.24272/j.issn.2095-8137.2024.028 -
BMC Pediatrics Sep 2023Children diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies...
BACKGROUND
Children diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies have highlighted differences in gut microbiota composition between individuals with ASD and healthy controls of similar ages. However, it's essential to recognize that these disparities may be influenced by cultural practices, dietary habits, and environmental factors.
METHODS
In this study, we collected fecal samples from both children diagnosed with ASD (n = 42) and healthy individuals (n = 41) residing in the southeastern coastal region of China. Subsequently, 16 S rRNA gene sequencing and advanced bioinformatics analyses were conducted to investigate the distinctive features of gut microbial communities within each group.
RESULTS
The ASD group consisted of 28 males and 14 females, with a median age of 5.8 years, while the control group included 25 males and 16 females, with a median age of 6.8 years. Among the 83 sequenced fecal samples, a total of 1031 operational taxonomic units (OTUs) were identified. These included 122 unique OTUs specific to the control group and 285 unique OTUs specific to the ASD group. Analyses of α-diversity and β-diversity unveiled significant differences in the abundance and composition of gut microbiota between the two groups. It was found that the dominant bacterial taxa in healthy individuals were UBA1819, Flavonifractor, and Bradyrhizobium. In contrast, the ASD group exhibited a prevalence of Streptococcus, Ruminococcus, and Ruminiclostridium. Further analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) showed significant differences in the metabolic functionalities of the gut microbiota between the two groups. Notably, the metabolic pathway related to alpha-linolenic acid (ALA) in the gut microbiota of the ASD group was notably diminished compared to the control group. Conversely, the ASD group demonstrated significantly elevated levels of metabolic pathways involving uncharacterized conserved proteins, aminoglycoside phosphotransferase, and inorganic pyrophosphatase compared to the control group.
CONCLUSIONS
Overall, these results confirm that there are significant differences in the gut microbiota structure between children with ASD and healthy controls in the southeast coastal region of China. This underscores the critical significance of delving into clinical interventions capable of mitigating the gastrointestinal and psychological symptoms encountered by children with ASD. A particularly encouraging path for such interventions lies in the realm of fecal microbiota transplantation, a prospect that merits deeper inquiry.
Topics: Female; Male; Child; Humans; Child, Preschool; Gastrointestinal Microbiome; Autism Spectrum Disorder; Microbiota; Anxiety; Constipation
PubMed: 37730588
DOI: 10.1186/s12887-023-04292-8