Fatty Acid Synthesis Research Articles

Rice Protein Peptides Alleviate Alcoholic Liver Disease via the PPARγ Signaling Pathway: Through Liver Metabolomics and Gut Microbiota Analysis.

Alcoholic liver disease (ALD) is the predominant type of liver disease worldwide, resulting in significant mortality and a high disease burden. ALD damages multiple organs, including the liver, gut, and brain, causing inflammation, oxidative stress, and fat deposition. In this study, we investigated the effects of rice protein peptides (RPP) on ALD in mice with a primary focus on the gut microbiota and liver metabolites. The results showed that administration of RPP significantly alleviated the symptoms of ALD in mice including adiposity, oxidative stress, and inflammation. The KEGG pathway shows that RPP downregulates the liver metabolite of capric acid and the metabolism of fatty acid biosynthesis compared with the MOD group. Mechanistically, RPP downregulated the PPARγ signaling pathway and suppressed the expression of fatty acid biosynthesis genes (FASN, ACC1, ACSL1, and ACSL3). Furthermore, two active peptides (YLPTKQ and PKLPR) with potential therapeutic functions for ALD were screened by Caco-2 cell modeling and molecular docking techniques. In addition, RPP treatment alleviates gut microbiota dysbiosis by reversing the F/B ratio, increasing the relative abundance of Alloprevotella and Alistipes, and upregulating the level of short-chain fatty acids. In conclusion, RPP alleviates ALD steatosis through the PPARγ signaling pathway by YLPTKQ and PKLPR and regulates gut microbiota.

Transcriptional Analysis of Different Cultivars and Genome-Wide Identification of FAD Gene Family in Tree Peony

The tree peony (Paeonia ostii), a newly recognized woody oil plant endemic to China, is noteworthy for its high content of unsaturated fatty acids (UFA), particularly alpha-linolenic acid (ALA). Fatty acid desaturases (FADs) are integral to plant development and defense mechanisms. Nonetheless, there is limited understanding of (i) the molecular mechanism underlying FA biosynthesis in various varieties during seed maturation and (ii) a genome-wide analysis of FAD family genes within the tree peony. We selected three distinct cultivars of tree peony for transcriptome sequencing and performed an extensive analysis of PoFAD genes. In total, 67,542 unigenes were acquired and annotated with six protein databases available to the public. Forty-one differentially expressed genes (DEGs) pertinent to FA biosynthesis and lipid metabolism were identified in this study. Notably, genes such as PoFAD2, PoFAD6, and PoSAD were found to be significantly upregulated, contributing to a differential linolenic acid and linoleic acid content across the three cultivars. Herein, 24 PoFADs from the P. ostii genome were recognized and categorized into four distinct clusters according to their conserved structural features. The distribution of PoFADs was found to be random and uneven across five chromosomes, indicating a complex genomic architecture. Six colinear gene pairs were found between P. ostii and V. vinifera, indicating a potential link due to their close relationship. Together, these findings significantly enhance our knowledge of the molecular processes governing fatty acid synthesis, elucidate the functional roles of the FAD gene family, and lay the groundwork for using genetic manipulation to boost lipid levels.

Identification and Functional Characterization of the FATP1 Gene from Mud Crab, Scylla paramamosain.

In mammals, fatty acid transport protein 1 (FATP1) plays important roles in cellular uptake and activation of long-chain fatty acid (LCFA), especially in processes of transportation, oxidation and triacylglycerol synthesis. However, the role of FATP1 in invertebrates, especially decapod crustaceans, is still poorly understood. In this study, the cDNA of a FATP1 gene from a decapod crustacean, mud crab Scylla paramamosain, was cloned and functionally characterized. The FATP1 gene encoded a polypeptide consisting of 643 amino acids that exhibits all the typical features of the FATP family and shares high homology with the other FATP orthologs of crustaceans. The relative mRNA expression levels of FATP1 were observed to be higher in metabolically active tissues such as hepatopancreas, stomach and gill than in other crab parts. Knockdown of the FATP1 mRNA in vivo significantly reduced triacylglycerols and total lipid levels in the hepatopancreas, accompanied by an increase in the expression of genes related to fatty acid transportation, allocation and hydrolysis, including long-chain acyl-CoA synthetase 3/4 (ACSL3/4) and carnitine palmitoyl transferase 1 (CPT1), and a decrease in the expression of genes related to fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the hepatopancreas. Furthermore, increased dietary n-3 long-chain polyunsaturated fatty acid (LC-PUFA) levels resulted in the up-regulation of the FATP1 expression in the hepatopancreas, accompanied by an increase in LC-PUFA content, especially eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), in both polar (PLs) and neutral lipids (NLs) in the hepatopancreas and muscles of crabs. These findings suggested that the FATP1 gene identified in S. paramamosain might play important roles in regulating long-chain fatty acid metabolism and deposition in crustaceans.

Retinoid X Receptor Signaling Mediates Cancer Cell Lipid Metabolism in the Leptomeninges.

Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC-and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs). We found evidence of local retinoic acid (RA) generation in both human leptomeningeal metastasis and mouse models in the form of elevated spinal fluid retinol and expression of RA-generating dehydrogenases within the leptomeningeal microenvironment. Stimulating LeptoM cells with RA induced expression of transcripts encoding de novo fatty acid synthesis pathway enzymes in vitro . In vivo , while deletion of Stra6 did not alter cancer cell leptomeningeal growth, knockout of Rxra/b/g interrupted cancer cell lipid biosynthesis and arrested cancer growth. These observations illustrate a mechanism whereby metastatic cancer cells awake locally-generated developmental cues for metabolically reprograming, suggesting novel therapeutic approaches.

High-fat diet promotes type 2 diabetes mellitus by disrupting gut microbial rhythms and short-chain fatty acid synthesis.

Diabetes ranks among the top 10 causes of death globally, with over 90% of individuals diagnosed with diabetes having type 2 diabetes mellitus (T2DM). It is acknowledged that a high-fat diet (HFD) poses a serious risk for T2DM. The imbalance of intestinal flora, mediated by HFD, can potentially exacerbate the onset and progression of T2DM. However, the impact of HFD on pathological indicators and the intestinal microbiome in the development of T2DM has not been systematically investigated. Therefore, a HFD mouse model and a T2DM mouse model were established, respectively, in this study. The role of HFD as a driving factor in the development of T2DM was assessed using various measures, including basic pathological indicators of T2DM, lipid metabolism, liver oxidative stress, intestinal permeability, levels of inflammatory factors, gut microbiota, and short-chain fatty acids (SCFAs). The findings indicated that HFD could influence the aforementioned measures to align with T2DM changes, but the contribution of HFD varied across different pathological metrics of T2DM. The impact of HFD on low-density lipoprotein cholesterol, glutathione peroxidase, malondialdehyde, and tumor necrosis factor-α did not show a statistically significant difference from those observed in T2DM during its development. In addition, regarding gut microbes, HFD primarily influenced the alterations in bacteria capable of synthesizing SCFAs. The notable decrease in SCFA content in both serum and cecal matter further underscored the effect of HFD on SCFA-synthesising bacteria in mice. Hence, this research provided a systematic assessment of HFD's propelling role in T2DM's progression. It was inferred that gut microbes, particularly those capable of synthesizing SCFAs, could serve as potential targets for the future prevention and treatment of T2DM instigated by HFD.

Expression of Genes Related to Meat Productivity, Metabolic and Morphological Significance of Broiler Chickens with the Use of Nutritional Phytochemicals.

The study aimed to analyze gene expression linked to skeletal muscle growth and lipid metabolism in broiler chickens fed with plant extracts. Five groups of chickens were formed: four experimental groups and one control group. The diets of the experimental groups were supplemented with different plant extracts: chicory, St. John's wort, maral root, and creeping thyme, whereas the control group received feed without phytobiotic compounds. Weekly weighings were conducted (n = 36). The chickens were slaughtered at day 26 for tissue sampling of four birds from each group. Gene expression (MYOG, MSTN, FASN) related to muscle growth and fatty acid synthesis was analyzed using the β-actin ACTB gene as a reference. Blood samples were taken at day 35 for biochemical analysis and anatomical dissection was performed. The study revealed that using plant extracts from chicory, thyme, and maral root increased MYOG gene activity by 4.21, 7.45, and 8.93 times, respectively. T. serpyllum extract boosted the MSTN gene by 10.93 times, impacting muscle growth regulation. FASN gene expression for fatty acid synthesis increased significantly by 18.22-184.12 times with plant extracts. The best results regarding meat productivity of chickens were obtained when using R. carthamoides extract. The results of the study will serve as a basis for further development of a phytocomposition designed to increase the meat productivity of broiler chickens in the production of environmentally safe poultry products.

Brown fat ATP-citrate lyase links carbohydrate availability to thermogenesis and guards against metabolic stress.

Brown adipose tissue (BAT) engages futile fatty acid synthesis-oxidation cycling, the purpose of which has remained elusive. Here, we show that ATP-citrate lyase (ACLY), which generates acetyl-CoA for fatty acid synthesis, promotes thermogenesis by mitigating metabolic stress. Without ACLY, BAT overloads the tricarboxylic acid cycle, activates the integrated stress response (ISR) and suppresses thermogenesis. ACLY's role in preventing BAT stress becomes critical when mice are weaned onto a carbohydrate-plentiful diet, while removing dietary carbohydrates prevents stress induction in ACLY-deficient BAT. ACLY loss also upregulates fatty acid synthase (Fasn); yet while ISR activation is not caused by impaired fatty acid synthesis per se, deleting Fasn and Acly unlocks an alternative metabolic programme that overcomes tricarboxylic acid cycle overload, prevents ISR activation and rescues thermogenesis. Overall, we uncover a previously unappreciated role for ACLY in mitigating mitochondrial stress that links dietary carbohydrates to uncoupling protein 1-dependent thermogenesis and provides fundamental insight into the fatty acid synthesis-oxidation paradox in BAT.

Synergistic Effect of Arbuscular Mycorrhizal Fungi and Germanium on the Growth, Nutritional Quality, and Health-Promoting Activities of Spinacia oleracea L.

Arbuscular mycorrhizal fungi (AMF) and the antioxidant germanium (Ge) are promising tools for boosting bioactive compound synthesis and producing healthier foods. However, their combined effect remains unexplored. This study demonstrates the synergistic impact of AMF and Ge on the growth, metabolite accumulation, biological activities, and nutritional qualities of Spinacia oleracea L. (spinach), a globally significant leafy vegetable. Individually, Ge and AMF increased biomass by 68.1% and 22.7%, respectively, while their combined effect led to an 86.3% increase. AMF and Ge also improved proximate composition, with AMF-Ge interaction enhancing crude fiber and mineral content (p < 0.05). Interestingly, AMF enhanced photosynthesis-related parameters (e.g., total chlorophyll) in Ge treated plants, which in turn increased carbohydrate accumulation. This accumulation could provide a route for the biosynthesis of amino acids, organic acids, and fatty acids, as evidenced by increased essential amino acid and organic acid levels. Consistently, the activity of key enzymes involved in amino acids biosynthesis (e.g., glutamine synthase (GS), methionine biosynthase (MS), lysine biosynthase (LS)) showed significant increments. Furthermore, AMF improved fatty acid levels, particularly unsaturated fatty acids in Ge-treated plants compared to the control. In addition, increased phenylalanine provided a precursor for the production of antioxidants (e.g., phenols and flavonoids), through the action of the enzyme phenylalanine ammonia-lyase (PAL), resulting in improved antioxidant activity gains as indicated by FRAP, ABTS, and DPPH assays. This study is the first to show that Ge enhances the beneficial effect of AMF on spinach, improving growth and nutritional quality, with promising implications for agricultural practices.

Effect of Hypoxia on the Gut Microflora of a Facultative Air-Breathing Loach Lepidocephalichthys guntea.

One of the main risks to fish health in an aquatic environment is hypoxia, which can either lead to respiratory failure or the emergence of various diseases in a fish population. This investigation examined the impact of hypoxia on the gut bacteria of a loach, Lepidocephalichthys guntea, which under the dissolve oxygen stress can gulp air from surface and breathe using its posterior intestine. High-throughput sequencing was used to examine the anterior and posterior parts of the gut of L. guntea during both normoxia and hypoxia. According to the community profiling of the gut bacteria, prolonged exposure to hypoxia increased the diversity and abundance of bacteria in the posterior part while decreasing both in the anterior part of the gut. Additionally, for both parts of the gut, the core microbiota showed a significant alteration during hypoxia. In correlation network analysis, a more interactive and intricate network was developed at normoxia. According to the comparative analyses of the gut bacteria, hypoxia causes more pronounced alterations in the posterior gut than the anterior gut at various taxonomic levels. As a consequence of hypoxia, several genera like Aeromonas, Pseudomonas, Plesiomonas, Acinetobacter, and Enterobacter were replaced by Streptococcus, Escherichia-Shigella, Janthinobacterium, and Clostridia. A surge in probiotic genera, including Bifidobacterium, Lactobacillus, Blautia, and Cetobacterium, was also seen. The fatty acid biosynthesis pathway was induced only in hypoxia, although all other metabolic pathways were present in both situations, albeit with fewer hits in hypoxia.

127aa encoded by circSpdyA promotes FA synthesis and NK cell repression in breast cancers.

Lipid metabolism reprogram plays key roles in breast cancer tumorigenesis and immune escape. The underlying mechanism and potential regulator were barely investigated. We thus established an in vivo tumorigenesis model, mice-bearing breast cancer cells were treated with an ordinary diet and high-fat diet, species were collected and subjected to circRNA sequence to scan the potential circRNAs regulating the lipid metabolism. CircSpdyA was one of the most upregulated circRNAs and had the potential to encode a 127-aa micro peptide (referred to as 127aa). 127 aa promotes tumorigenesis through promoting the fatty acid de novo synthesis by directly binding to FASN. Single-cell sequence indicated 127aa inhibited NK cell infiltration and function. This was achieved by inhibiting the transcription of NK cell activators epigenetically. Moreover, lipid-laden from 127aa positive cancer cells transferred to NK cells inhibited the cytotoxicity. Taken together, circSpdyA encoded 127aa promotes fatty acid de novo synthesis through directly binding with FASN and induced NK cell repression by inhibiting the transcription of NK cell activators.

Comparative Transcriptomic Profiling of Brain and Liver in Phoenix Barbs (Spinibarbus denticulatus denticulatus) with Differential Growth Rates

Phoenix barb (Spinibarbus denticulatus denticulatus) is a notable fish species in South China and is valued for its ecological and economic importance. To elucidate the molecular basis underlying its growth, we collected transcriptome profiles from the brains and livers of individual fish with different growth rates and compared differentially expressed genes (DEGs) at 3 and 9 months after hatching (MAH). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the pathways associated with growth were predominantly enriched in fatty acid biosynthesis, AMPK signaling, PI3K-Akt signaling, estrogen signaling, and protein metabolism. Notably, a greater number of DEGs from the fast-growing group were associated with these pathways at the early growth stage (3 MAH) than at the later stage (9 MAH). Real-time quantitative PCR results further validated that the genes involved in these pathways exhibited higher expression levels in fast-growing samples. This study enhances our understanding of the genetic mechanisms underlying growth rate differences and provides valuable genetic resources for future growth-related molecular breeding programs of phoenix barbs.

Role of ACSBG1 in Brain Lipid Metabolism and X-Linked Adrenoleukodystrophy Pathogenesis: Insights from a Knockout Mouse Model.

"Bubblegum" acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during mouse brain development, facilitating the activation of long-chain fatty acids (LCFA) and their incorporation into lipid species that are crucial for brain function. ACSBG1 converts LCFA into acyl-CoA derivatives, supporting vital metabolic processes. Fruit fly mutants lacking ACSBG1 exhibited neurodegeneration and had elevated levels of very long-chain fatty acids (VLCFA), characteristics of human X-linked adrenoleukodystrophy (XALD). To explore ACSBG1's function and potential as a therapeutic target in XALD, we created an ACSBG1 knockout (Acsbg1-/-) mouse and examined the effects on brain FA metabolism during development. Phenotypically, Acsbg1-/- mice resembled wild type (w.t.) mice. ACSBG1 expression was found mainly in tissue affected pathologically in XALD, namely the brain, adrenal gland and testis. ACSBG1 depletion did not significantly reduce the total ACS enzyme activity in these tissue types. In adult mouse brain, ACSBG1 expression was highest in the cerebellum; the low levels detected during the first week of life dramatically increased thereafter. Unexpectedly, lower, rather than higher, saturated VLCFA levels were found in cerebella from Acsbg1-/- vs. w.t. mice, especially after one week of age. Developmental changes in monounsaturated ω9 FA and polyunsaturated ω3 FA levels also differed between w.t. and Acsbg1-/- mice. ACSBG1 deficiency impacted the developmental expression of several cerebellar FA metabolism enzymes, including those required for the synthesis of ω3 polyunsaturated FA, precursors of bioactive signaling molecules like eicosanoids and docosanoids. These changes in membrane lipid FA composition likely affect membrane fluidity and may thus influence the body's response to inflammation. We conclude that, despite compelling circumstantial evidence, it is unlikely that ACSBG1 directly contributes to the pathology of XALD, decreasing its potential as a therapeutic target. Instead, the effects of ACSBG1 knockout on processes regulated by eicosanoids and/or docosanoids should be further investigated.

Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase.

Human acetyl-coenzyme A (CoA) carboxylases (ACCs) catalyze the carboxylation of acetyl-CoA, which is the rate-limiting step in fatty acid synthesis. The molecular mechanism underlying the dynamic organization of ACCs is largely unknown. Here, we determined the cryo-electron microscopy (EM) structure of human ACC1 in its inactive state, which forms a unique filament structure and is in complex with acetyl-CoA. We also determined the cryo-EM structure of human ACC1 activated by dephosphorylation and citrate treatment, at a resolution of 2.55 Å. Notably, the covalently linked biotin binds to a site that is distant from the acetyl-CoA binding site when acetyl-CoA is absent, suggesting a potential coordination between biotin binding and acetyl-CoA binding. These findings provide insights into the structural dynamics and regulatory mechanisms of human ACCs.

Multi-omics revealed antibacterial mechanisms of licochalcone A against MRSA and its antimicrobic potential on pork meat

Licorice flavonoids (LFs) exhibit potent antibacterial activities against Gram-positive bacteria. However, the related mechanism remains unclear. This study aims to illustrate the mechanisms of licochalcone A (LA), a main flavonoid in LFs, against methicillin-resistant Staphylococcus aureus (MRSA). The anti-MRSA effect of LA was comprehensively investigated by a combination of proteomics and metabolomics studies. Meanwhile, LA was loaded in glycyrrhizin (GA) micelles (GA@LA micelles) to improve its water solubility. The results demonstrated that LA could disrupt the arginine metabolism and cause the accumulation of intracellular ROS in MRSA. In addition, LA could inhibit the expression of glucokinase in MRSA, which affect the synthesis of ATP, fatty acids, and peptidoglycan. GA@LA micelles have the latent ability to inhibit the growth of MRSA on fresh pork.

Metabolic changes in response to food intake in somatostatin 1.1 deficient zebrafish

Somatostatin is a multifunctional hormone with several genes in teleost fishes. A zebrafish CRISPR/Cas9 knockout of the somatostatin 1.1 (sst1.1) with persistent hyperglycaemia and hyperlipidaemia displayed reduced fecundity when fed brine shrimp ad libitum. Here, we investigated the effect of feeding brine shrimp one to three times a day on fecundity and liver transcriptomics of the sst1.1 mutant compared to their wild-type siblings to unravel molecular pathways associated with the phenotype. We find that the sst1.1 deficient zebrafish had high mortality when fed at the highest rate and that in both genotypes, growth and fecundity were proportional to food intake. Although glucose and cholesterol decreased substantially at the lowest level of feeding, they were still higher in the mutant than in the wild-type zebrafish. Furthermore, sst1.1 deficiency had a small but significant effect on the hepatic expression of protein, carbohydrate, and fatty acid biosynthesis genes, contributing to the mutant's diabetic phenotype.

Machine learning-aided microRNA discovery for olive oil quality.

MicroRNAs (miRNAs) are key regulators of gene expression in plants, influencing various biological processes such as oil quality and seed development. Although, our knowledge about miRNAs in olive (Olea europaea L.) is progressing, with several miRNAs being identified in previous studies, but most of these reported miRNAs have been predicted without the aid of a reference genome, primarily due to limited genome accessibility at the time. However, significant knowledge gaps still need to be improved in this area. This study addresses the complexities of miRNA detection in olive, using a high quality reference genome and a combination of genomics and machine learning-based methods. By leveraging random forest and support vector machine algorithms, we successfully identified 56 novel miRNAs in olive, surpassing the limitations of conventional homology-based methods. Our subsequent analysis revealed that some of these miRNAs are implicated in the regulation of key genes involved in oil quality. Within the context of oil biosynthesis pathways, the novel miRNA Oeu124369 regulates fatty acid biosynthesis by targeting acetyl-CoA acyltransferase 1 and palmitoyl-protein thioesterase, thereby influencing the production of acetyl-CoA and palmitic acid, respectively. These findings underscore the power of machine learning in unraveling the complex miRNA regulatory network in olive and provide a high quality miRNA resource for future research aimed at improving olive oil production by exploring the target genes of the identified miRNAs to understand their role and their biological processes.

Activity of the Caged Xanthone Morellic Acid against Vancomycin-Resistant Enterococcus Infection by Targeting the Bacterial Membrane.

Vancomycin-resistant Enterococcus (VRE) is an important nosocomial opportunistic pathogen that is associated with multidrug resistance. Here, we demonstrate that morellic acid inhibits VRE by restoring its sensitivity to vancomycin and ampicillin with low drug resistance and efficient biofilm clearance effects. Morellic acid binds to inner membrane phospholipids, such as phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) of VRE, such that the fluidity and proton-motive force (PMF) interfere with the damaged inner membrane, causing intracellular reactive oxygen species (ROS) accumulation and bacterial death. Transcriptional analyses supported this effect on inner membrane-related pathways such as fatty acid biosynthesis and glycerophospholipid metabolism. Moreover, morellic acid significantly eliminated residual bacteria in the spleen, liver, kidneys, and abdominal effusion in mice. Our findings indicate the potential applications of morellic acid as an antibacterial agent or adjuvant for treating VRE infections.

O-GlcNAcylation of ATP-citrate lyase couples glucose supply to lipogenesis for rapid tumor cell proliferation

Elevated lipid synthesis is one of the best-characterized metabolic alterations in cancer and crucial for membrane expansion. As a key rate-limiting enzyme in de novo fatty acid synthesis, ATP-citrate lyase (ACLY) is frequently up-regulated in tumors and regulated by posttranslational modifications (PTMs). Despite emerging evidence showing O-GlcNAcylation on ACLY, its biological function still remains unknown. Here, we observed a significant upregulation of ACLY O-GlcNAcylation in various types of human tumor cells and tissues and identified S979 as a major O-GlcNAcylation site. Importantly, S979 O-GlcNAcylation is required for substrate CoA binding and crucial for ACLY enzymatic activity. Moreover, it is sensitive to glucose fluctuation and decisive for fatty acid synthesis as well as tumor cell proliferation. In response to EGF stimulation, both S979 O-GlcNAcylation and previously characterized S455 phosphorylation played indispensable role in the regulation of ACLY activity and cell proliferation; however, they functioned independently from each other. In vivo, streptozocin treatment- and EGFR overexpression-induced growth of xenograft tumors was mitigated once S979 was mutated. Collectively, this work helps comprehend how cells interrogate the nutrient enrichment for proliferation and suggests that although mammalian cell proliferation is controlled by mitogen signaling, the ancient nutrition-sensing mechanism is conserved and still efficacious in the cells of multicellular organisms.

Effect of host breeds on gut microbiome and fecal metabolome in commercial pigs

BackgroundGut microbial composition and its metabolites are crucial for livestock production performance. Metabolite profiles from autopsied biospecimens provide vital information on the basic mechanisms that affect the overall health and production traits in livestock animals. However, the role of the host breed in the gut microbiome and fecal metabolome of commercial pigs remains unclear. In this work, differences in microbiota composition among three commercial pig breeds Duroc, Yorkshire, and Landrace were measured by 16S rRNA gene sequencing. Fecal metabolite compositions of the three pig breeds were detected using untargeted metabolomics.ResultsThere were significant differences in the gut microbiomes of the three species, indicating that host breed affects the diversity and structure of gut microbiota. Several breed-associated microorganisms were identified at different taxonomic levels. Notely, most microbial taxa were annotated as Lactobacillacea, Muribaculaceae, and Oscillospiraceae. Several bacteria, including Lactobacillus, Subdoligranulum, Faecalibacterium, Oscillospira, Oscillospiraceae_UCG-002, and Christensenellaceae_R-7_group, could be considered as biomarkers for improving the backfat thickness (BF) for commercial pigs. Additionally, KEGG analysis of gut microbiota further revealed that arginine biosynthesis, pyruvate metabolism, and fatty acid biosynthesis varied greatly among pig breeds. Multiple gut bacterial metabolites (e.g., spermidine, estradiol, and palmitic acid) were identified as breed-associated. Mediation analysis ultimately revealed the cross-talk among gut microbiota, metabolites, and BF thickness, proclaiming that the microbial and metabolic biomarkers identified in this study could be used as biomarkers for improving BF phenotype.ConclusionsThis work provides vital insights into breed effects on gut microbiota and metabolite compositions of commercial pigs and uncovers potential biomarkers that are significant for pig breed improvement.

FUT2 promotes colorectal cancer metastasis by reprogramming fatty acid metabolism via YAP/TAZ signaling and SREBP-1

Colorectal cancer (CRC) ranks as the second most lethal cancer worldwide because of its high rate of metastasis, and approximately 20% of CRC patients have metastases at initial diagnosis. Metabolic reprogramming, a hallmark of cancer cells, has been implicated in the process of metastasis. We previously demonstrated that fucosyltransferase 2 (FUT2) promotes the malignancy of CRC cells, however, the underlying mechanisms remain unclear. Here, bioinformatic analysis revealed that FUT2 is associated with the malignant phenotype and fatty acid metabolism in CRC. FUT2 knockdown decreased glucose uptake and de novo fatty acid synthesis, which in turn inhibited the proliferation and metastasis of CRC cells. Mechanistically, FUT2 promotes YAP1 nuclear translocation and stabilizes mSREBP-1 by fucosylation, thus promoting de novo fatty acid synthesis in CRC cells. In summary, this study demonstrates that FUT2 promotes the proliferation and metastasis of CRC cells by reprogramming fatty acid metabolism via YAP/TAZ signaling and SREBP-1, indicating that FUT2 might be a potential target for developing therapeutic strategies against CRC.