Fatty Acid Metabolism Research Articles

Perfluorooctane sulfonate (PFOS) exposure and alcohol-associated liver disease severity in a mouse chronic-binge ethanol feeding model.

Perfluorooctane sulfonate (PFOS) exposure and alcohol-associated liver disease severity in a mouse chronic-binge ethanol feeding model.

Fatty acid metabolism after short-term fasting: POMC response and EPA signal maintain homeostasis in tilapia

Detecting and responding to fluctuations in fatty acid levels is crucial for maintaining the homeostasis of fatty acid metabolism. This study examined changes in neuropeptide levels and fatty acid sensing systems in tilapia following 24-hour fasting. Subsequently, an EPA compensation experiment was conducted to examine the regulatory effects of hypothalamic neuropeptides on feeding activity, fatty acid sensing systems activation, and alterations in AMPK and AKT signaling pathways in tilapia. After fasting, the neuropeptide Y signals in the preglomerular nucleus region increased significantly, while the POMC in the lateral tuberal nucleus significantly decreased. There was a significant increase in most long-chain fatty acids, excluding the EPA which declined. Fasting activates fatty acid sensing systems regulated by fatty acid metabolism and mitochondrial activity in the hypothalamus, and those regulated by CD36, mitochondrial activity and PKC in the liver. However, it inhibited systems regulated by fatty acid metabolism and lipoprotein lipase in the liver. Intraperitoneal EPA injection raised pomc mRNA levels in the hypothalamus after short-term fasting and curtailed food intake. EPA compensation inhibited the liver fatty acid metabolism, CD36, and mitochondrial activity-related fatty acid sensing systems, and lipoprotein lipase-regulated fatty acid sensing systems in the hypothalamus while activating lipoprotein lipase-regulated fatty acid sensing systems in the liver. Moreover, EPA suppressed the AMPK pathway in both tissues. Following fasting, serum EPA levels decreased, accompanied by lower POMC in the brain and activation of the fatty acid sensing systems in hypothalamus and liver. EPA compensation inhibited the AMPK pathway, increased pomc mRNA in the hypothalamus and suppressed food intake as a satiation factor. This research offers insights into how the central nervous system and peripheral tissues respond to fatty acid levels during hunger in tilapia.

Impact of the 294 bp SINE Insertion in 5’UTR of the GLYATL3 Gene on Gene Expression and Phenotypic Variation

SINEs are one type of the most frequently found DNA repetitive sequences in the eukaryotic genome. The polymorphism generated by SINE insertion may affect proximal host genes and even cause phenotypic variations in domestic animals. Glycine N-acyltransferase-like 3 (GLYATL3) is a member of the N-acyltransferase family which may play a role in amino acid and fatty acid metabolism. Previous studies have identified short interspersed nuclear element (SINE) insertion sites in the 5’UTR region of GLYATL3. This study investigated the effects of the 294 bp SINE insertion on GLYATL3 expression and phenotypic variation. The polymerase chain reaction (PCR) was used to determine the distribution of GLYATL3-SINE-RIP in 15 pig breeds. SINE insertions were absent in hybrid pigs and present in all purebred pigs. Correlation analysis further revealed significant differences in SINE+/+ and SINE−/− individuals when they reached 30 kg of body weight. In light of these findings, qPCR revealed that the SINE insertion significantly increased GLYATL3 expression in the cerebellum of Mi pigs. Additionally, dual-luciferase reporter assays confirmed that the SINE insertion significantly enhanced the activity of the Oct4 promoter. Preliminary evidence indicates the SINE insertion may modulate an increase in the growth rate of pigs through transcriptional regulation of GLYATL3. As a new type marker, this SINE-insertion polymorphism may assist genetic selection to optimize growth traits in porcine breeding programs.

Fatty acid metabolism suppresses neonatal cardiomyocyte proliferation by increasing PDK4 and HMGCS2 expression through PPARδ.

Cardiomyocytes lose their capacity to regenerate immediately after birth. Simultaneously, cardiomyocytes change energy metabolism from glycolysis to oxidative phosphorylation, especially using fatty acids. Accumulating evidence has revealed that fatty acid metabolism weakens the proliferative ability of cardiomyocytes. However, its underlying molecular mechanism remains unclear. In this study, we investigated how fatty acid metabolism contributes to cell cycle regulation in neonatal cardiomyocytes. Cultured neonatal rat cardiomyocytes (NRCMs) were treated with a fatty acid mixture (FA) consisting of palmitic and oleic acids containing L-carnitine. The FA treatment increased not only β-oxidation-related enzymes but also pyruvate dehydrogenase kinase 4 (PDK4), a fatty acid metabolism regulator, and HMG-CoA synthase 2 (HMGCS2), a ketogenic factor. Moreover, Ki67-positive proliferative NRCMs were reduced by the FA, indicating that fatty acids suppress the NRCM cell cycle. GW501516, a peroxisome proliferator-activated receptor δ (PPARδ) activator, also upregulated fatty acid metabolism genes and disturbed NRCM proliferation, whereas GSK3787, a PPARδ inhibitor, recovered FA-induced the cell cycle arrest. Furthermore, overexpression of PDK4 or HMGCS2 using a lentiviral vector suppressed cell cycle activity in NRCMs, and silencing either gene regained cell cycle even in FA-rich condition. In conclusion, fatty acid metabolism increased PDK4 and HMGCS2 via PPARδ activation and suppressed NRCM proliferation.

Disruption of the rpfB Gene Impairs Growth and Virulence in Cronobacter sakazakii through Downregulation of the Shikimate Pathway.

The rpfB gene, encoding long-chain acyl-CoA synthetase, plays an essential role in the fatty acid metabolism of Cronobacter sakazakii, a pathogenic bacterium known to cause neonatal infections. Here, we investigate the functional consequences of rpfB gene knockout and its effect on bacterial growth and virulence. Our findings demonstrate that rpfB deletion leads to significantly reduced bacterial growth and virulence in a murine infection model. Proteomic analysis revealed that the disruption of rpfB markedly downregulates key enzymes in the shikimate pathway, including aroA and aroK, which are essential for the biosynthesis of aromatic amino acids. Supplementation with aromatic amino acids restored the growth defect, highlighting the critical link between fatty acid metabolism and the shikimate pathway. These results uncover a novel regulatory role for rpfB in coordinating metabolic networks that control bacterial growth and virulence. This study provides a new understanding of the metabolic mechanisms underlying C. sakazakii pathogenicity and identifies possible metabolic targets for antimicrobial development.

Integrated multi-omics analysis of metabolome and transcriptome profiles during bovine adipocyte differentiation reveals functional divergence of FADS2 isoforms in lipid metabolism regulation

BackgroundFat metabolism plays an important role in animal health and economic benefits. However, the changes in gene expression and metabolites during fat metabolism have not been systematically studied in bovine.ResultsThis study integrates transcriptomic and metabolomic strategies to delineate the metabolic and gene expression profiles during the adipogenesis of bovine preadipocytes in four different stages. Totally, we identified 328 differentially expressed metabolites (DEMs) and 5257 differentially expressed genes (DEGs) during adipogenesis. Functional enrichment of both DEMs and DEGs highlighted the important roles of fatty acid metabolic pathways. By integrating transcriptomic and metabolomic data, we identified key genes potentially regulating fatty acid metabolism, including FADS2, ACOT7 and ACOT2. We further applied comparison for the functional differences between two FADS2 isoforms (FADS2-T0 and FADS2-T2). The results proved that the lipid metabolism regulated by FADS2-2 has changed due to the loss of 46 amino acids with a transmembrane domain, which finally altering its promoting effect on bovine fat deposition.ConclusionsIn summary, our research provides important resources and key candidate genes for a systematic understanding of the changes in gene expression and lipid metabolism during the process of fat deposition.

Lactiplantibacillus brownii strain MH-1 prolongs healthspan and improves stress resistance in Caenorhabditis elegans.

Lactiplantibacillus brownii was first discovered in 2023. We previously isolated L. brownii strain MH-1 from homemade pickled Chinese cabbage in Hiroshima Prefecture, Japan, and performed whole-genome sequencing. In this study, we examined the beneficial effects of L. brownii strain MH-1 on a host using C. elegans. MH-1 and heat-killed MH-1 extended the lifespan and also alleviated motility decline during aging in worms. Feeding MH-1 to nematodes indicated its presence in the intestinal tract with no change in body or brood sizes, suggesting that dietary restrictions did not occur. There were no significant differences in intestinal barrier enhancement or fat accumulation in MH-1-fed C. elegans. The stress response of C. elegans was enhanced by MH-1 for oxidative stress tolerance. MH-1 increased the expression of genes involved in defense response and lipid catabolism. These results demonstrate the beneficial effects of MH-1 on nematodes and its potential use as a probiotic.

Telomere to telomere flax (Linum usitatissimum L.) genome assembly Unlocks insights beyond fatty acid metabolism pathways

Abstract One of China's most important resources is flax (Linum usitatissimum L.), an ancient crop with significant nutritional and therapeutic benefits. Despite its importance, existing flax reference genomes remain incomplete, with many unassembled sequences. Here, we report a gapless 482.51 Mb telomere-to-telomere (T2T) flax genome assembly, predicting 46,634 genes, of which 42,805 were functionally annotated. Repetitive sequences constitute 60.05% of the genome, and we identified 30 telomeres and 15 centromeres across the chromosomes. Whole-genome duplication (WGD) events were detected at approximately 11.5, 53.5, and 114 million years ago (MYA) based on synonymous substitution rates (Ks). The T2T assembly enabled the reconstruction of the fatty acid metabolic pathway, identifying 49 related genes, including 6 newly annotated ones. Furthermore, genomic co-localization was observed between fatty acid metabolism pathway-related genes and transposable elements, suggesting that functional differentiation of these genes in flax evolution may have occurred through transposon-mediated duplication events. Phylogenetic analysis of SAD and FAD gene families revealed that FAD genes segregate into FAD2 and FAD3/7/8 subfamilies. Gene structure and motif analyses demonstrated conserved exon-intron architectures and motif organization within each phylogenetic clade of SAD and FAD genes. Promoter region characterization identified numerous cis-acting elements responsive to phytohormones (MeJA and abscisic acid) and abiotic stresses (low temperature and anaerobic induction) in both SAD and FAD genes. Our knowledge of the evolution of the flax genome is improved by this excellent genome assembly, which also offers a strong basis for enhancing agricultural attributes and speeding up molecular breeding.

Accumulation of long-chain unsaturated fatty acids in the airway inflammatory microenvironment drives eosinophil etosis and corticosteroid resistance

BackgroundEosinophilic inflammation is a feature of chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with eosinophilic CRSwNP (ENP) tend to be refractory and prone to recurrence. Although there is increasing evidence linking lipid metabolic irregularities to eosinophilia, the particular lipid responsible for promoting eosinophilic inflammation and the precise molecular mechanisms involved remain unclear.MethodsLipidomic atlas and metabolic pathway enrichment were identified by liquid chromatography-tandem mass spectrometry and RNA sequencing, respectively. Eosinophil extracellular trap cell death (EETosis) was detected by immunofluorescence microscopy and transmission electron microscopy. Functional analyses were performed on purified eosinophils.ResultsThe unbiased lipidomic atlas identified a specific accumulation in long-chain fatty acids (LCFAs) in ENP. Consistently, RNA-seq analysis confirmed the enrichment in long-chain unsaturated fatty acid metabolism pathway in ENP. In this lipid-rich airway inflammatory environment, EETosis including ETotic eosinophils, EETs release and Charcot-Leyden crystals (CLCs) generation was enhanced in ENP, and associated with disease severity. Further, we found that both saturated and unsaturated LCFAs, such as arachidonic acid, are critical fuel sources to trigger eosinophil activation and filamentous DNA release, whereas only arachidonic acid could induce crystalline Galectin10 (CLCs). Mechanistically, arachidonic acid induces EETosis through a mechanism independent of reactive oxygen species but the IRE1α/XBP1s/PAD4 pathway. Both the long-acting dexamethasone and short-acting hydrocortisone, while facilitate eosinophil apoptosis, are ineffective to block arachidonic acid-induced EETosis.ConclusionsOur findings demonstrate a previously unknown role of the LCFA arachidonic acid in mediating EETosis and glucocorticoid insensitivity to drive ENP progression, which may lead to novel insights regarding the treatment of patients with refractory eosinophilic inflammation.

Cellular metabolomics study in colorectal cancer cells and media following treatment with 5-fluorouracil by gas chromatography-tandem mass spectrometry.

Metabolic reprogramming is a distinctive characteristic of colorectal cancer (CRC) which provides energy and nutrients for rapid proliferation. Although numerous studies have explored the rewired metabolism of CRC, the metabolic alterations occurring in CRC when the cell cycle is arrested by treatment with 5-fluorouracil (5-FU), an anticancer drug that arrests the S phase, remain unclear. A systematic profiling analysis was conducted as ethoxycarbonyl/methoxime/tert-butyldimethylsilyl derivatives using gas chromatography-tandem mass spectrometry in HT29 cells and media following 5-FU treatment in a concentration- and time-dependent manner. In HT29 cells of 24h after 5-FU treatment (3-100μM) and 48h after 5-FU treatment (1-10μM), six amino acids, including valine, leucine, isoleucine, serine, glycine, and alanine and two organic acids, including pyruvic acid and lactic acid, were significantly increased compared to the DMSO-treated group. However, 48h after 5-FU treatment (30-100μM) in HT29 cells, the levels of these metabolites decreased along with an approximately 50% reduction in viability, an increase in the level of reactive oxygen species, induction of cycle arrest in the G1 phase, and the induction of apoptosis. On the other hand, the levels of fatty acids showed a continuous increase in HT29 cells 48h after 5-FU treatment (1-100μM). In the media, the decreased availabilities in the cellular uptake of nutrient metabolites, including valine, leucine, isoleucine, serine, and glutamine, were observed at 48h after 5-FU treatment in a dose-dependent manner. It is assumed that there is a possible shift in energy dependence from the tricarboxylic acid cycle to fatty acid metabolism. Thus, metabolic profiling analysis revealed altered energy metabolism in CRC cells following 5-FU treatment.

Effects of combination of krill oil with curcumin and/or silymarin on mouse non-alcoholic fatty liver disease.

No effective pharmacological therapy is available for non-alcoholic fatty liver disease. The use of natural products is an alternative therapeutic. The natural antioxidants such as curcumin and silymarin are used in clinical trials against non-alcoholic fatty liver disease, which are hampered by their membrane permeability and consequent low absorption. The amphipathic phospholipid is beneficial to their absorption and antarctic krill oil contains rich phospholipids. We demonstrated that the mixture (antarctic krill oil, curcumin and silymarin) exhibited remarkable roles in inhibiting high-fat diet-induced mouse non-alcoholic fatty liver disease. The effect of the mixture on high-fat diet-induced mouse non-alcoholic fatty liver disease were associated with their regulating the transcriptions of genes related to triglyceride synthesis and fatty acid metabolism, inflammation-related factors, and with the endogenous antioxidant capacity, which might suggest a new choice for inhibiting human non-alcoholic fatty liver disease.

Cardamonin suppresses mTORC1/SREBP1 through reducing Raptor and inhibits de novo lipogenesis in ovarian cancer.

Metabolic reprogramming is a hallmark of cancer and de novo lipogenesis (DNL) accelerates the progression of ovarian cancer. In this study, we investigated the effects of cardamonin, a natural compound potential to suppress various malignancies, on the lipid anabolism in ovarian cancer. Cell proliferation was assessed using CCK-8 and clone formation assay. Cell apoptosis was detected by flow cytometry with Annexin V-FITC/PI staining and mitochondrial membrane potential (MMP) was measured with JC-10 probe. Free fatty acids (FFA) was measured by fluorescence using acyl-CoA oxidation and carnitine palmitoyl transferase-1 (CPT-1) activity was analyzed by spectrophotometric assay using palmitoyl-CoA and DTNB (5,5'-dithio-bis-(2-nitrobenzoic acid)) reaction. mRNA expression was measured by Quantitative Real-Time PCR. Protein expression was analyzed through western blotting and immunofluorescence. Raptor was knocked down by shRNA and Raptor was overexpressed by lentiviral transfection. The antitumor effect of cardamonin was evaluated using a xenotransplantation tumor bearing mouse model. Cardamonin suppressed the cell proliferation, induced cell apoptosis and triggered mitochondrial damage in ovarian cancer cells. Cardamonin inhibited the protein expression of sterol regulatory element binding protein 1 (SREBP1) and its downstream lipogenic enzymes and decreased FFA content and CPT-1 activity. Additionally, cardamonin inhibited the activation of mechanistic target of rapamycin complex 1 (mTORC1) and expression of regulatory-associated protein of mTOR (Raptor). Raptor knockdown abolished the inhibitory effect of cardamonin on mTORC1 and SREBP1. Furthermore, cardamonin inhibited mTORC1 activation and lipogenic proteins expression induced by Raptor overexpression. Cardamonin reduced the tumor growth and fatty acid synthase of the tumors, as evidenced by decreased expression of Ki-67 and FASN. It suggests that cardamonin suppresses mTORC1/SREBP1 through reducing the protein level of Raptor and inhibits DNL of ovarian cancer.

Nontargeted metabolomics analysis in allergic conjunctivitis.

PurposeAllergic conjunctivitis is a disease with a high prevalence in the world. In this study, untargeted metabolomics analyzes were performed to investigate the metabolic profile of the disease in serum samples of allergic conjunctivitis patients.MethodsSerum samples were obtained from 20 allergic conjunctivitis patients and 20 healthy subjects. Untargeted metabolomics analyzes were performed by LC/Q-TOF/MS (liquid chromatography quadrupole time-of-flight mass spectrometry) method. Data collection, classification and identification were performed with the METLIN database and XCMS.ResultsA total of 152 different metabolites were identified and labeled. All annotated metabolites exhibited a 1.5-fold change (increase or decrease) and had a p-value of less than or equal to 0.05 when comparing groups. All statistical data indicated that the model was statistically significant and the p-value is less than or equal to 0.05. All annotated metabolites were evaluated and pathway analysis were performed with significantly altered metabolites.ConclusionIn this study, significant differences in histamine, fatty acid, sphingolipid, purine, vitamin and melatonin metabolism were observed in allergic conjunctivitis patients. It has been determined that disruption of the cell barrier due to changes in fat metabolism, activation of inflammation pathways and irregularity in sphingolipid metabolism play an important role in the underlying mechanisms of allergic conjunctivitis.

Metabolomics as a tool for understanding and treating triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous variant of breast cancer distinguished by a lack of targeted therapies, posing significant challenges in diagnosis and treatment. Metabolomics, the comprehensive study of small compounds in biological systems, has been identified as an instrument for revealing the metabolic underpinnings of TNBC. This review highlights recent advancements in metabolomic approaches, such as mass spectrometry and nuclear magnetic resonance, which have identified metabolic vulnerabilities, resistance mechanisms, and potential therapeutic targets. Key findings include alterations in fatty acid, amino acid, and glutathione metabolism, along with hypoxia-driven metabolic reprogramming that contributes to disease progression. The combination of metabolomics with multi-omics techniques, supported by advanced computational methods such as machine learning, offers a pathway to overcome challenges in data standardization and biological complexity. Emerging strategies, including the use of artificial intelligence and multidimensional omics approaches, are paving the way for personalized medicine by enabling the discovery of novel biomarkers and targeted therapies. Despite these advances, significant hurdles remain, including the need for robust data standardization, validation of findings in diverse patient cohorts, and seamless integration with clinical workflows. By addressing these challenges, metabolomics has the potential to revolutionize TNBC management, offering tools for early detection, precision therapy, and improved patient outcomes. This review underscores the importance of interdisciplinary collaboration to translate metabolomic insights into actionable clinical applications.

Hyperoside modulates bile acid and fatty acid metabolism, presenting a potentially promising treatment for non-alcoholic fatty liver disease.

Hyperoside modulates bile acid and fatty acid metabolism, presenting a potentially promising treatment for non-alcoholic fatty liver disease.

Cordycepin extends the longevity of Caenorhabditis elegans via antioxidation and regulation of fatty acid metabolism.

Cordycepin extends the longevity of Caenorhabditis elegans via antioxidation and regulation of fatty acid metabolism.

Adsorption of dibutyl phthalate by multi-walled carbon nanotubes aggravates hemogram, liver and kidney damage in rats.

Adsorption of dibutyl phthalate by multi-walled carbon nanotubes aggravates hemogram, liver and kidney damage in rats.

Metabolomic analysis elucidates the dynamic changes in aroma compounds and the milk aroma mechanism across various portions of tea leaves during different stages of Oolong tea processing.

Metabolomic analysis elucidates the dynamic changes in aroma compounds and the milk aroma mechanism across various portions of tea leaves during different stages of Oolong tea processing.

AMPK Signaling Pathway Regulates Tendon Regeneration via Fatty Acid Metabolism.

Tendon and ligament injuries are the most common musculoskeletal injuries, and their regeneration is a complex process due to the poor natural healing ability of these tissues. The current therapies for tendon repair are limited in efficacy and their cellular and molecular mechanisms remain unclear. In this study, we identified AMP-activated protein kinase (AMPK) as a markedly upregulated factor in newborn tendons with high regenerative capacity. Both in vivo and in vitro experiments demonstrated that treatment with dorsomorphin, an AMPK inhibitor, significantly decreased the tendon healing potential. Further analyses revealed that carnitine palmitoyltransferase 1A, a key enzyme, is a putative downstream target of AMPK and is closely associated with the proliferation and tenogenic differentiation of tendon stem/progenitor cells. Collectively, we highlight the essential role of AMPK in tendon repair and propose a potential therapeutic intervention for tendon injuries.

Transcriptome analysis of the ovary and testis of the pearl oyster Pinctada fucata: Identification of genes and pathways involved in gonadal development.

Transcriptome analysis of the ovary and testis of the pearl oyster Pinctada fucata: Identification of genes and pathways involved in gonadal development.