Lipid Metabolism-related Genes Research Articles

Identification of potential key lipid metabolism-related genes involved in tubular injury in diabetic kidney disease by bioinformatics analysis.

Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-related genes associated with tubular injury in DKD by utilizing bioinformatics approaches. Differentially expressed genes (DEGs) between control and DKD tubular tissue samples were screened from the Gene Expression Omnibus (GEO) database, and then were intersected with lipid metabolism-related genes. Hub genes were further determined by combined weighted gene correlation network analysis (WGCNA) and protein-protein interaction (PPI) network. We performed enrichment analysis, immune analysis, clustering analysis, and constructed networks between hub genes and miRNAs, transcription factors and small molecule drugs. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of hub genes. We validated the relationships between hub genes and DKD with external datasets and our own clinical samples. There were 5 of 37 lipid metabolism-related DEGs identified as hub genes. Enrichment analysis demonstrated that lipid metabolism-related DEGs were enriched in pathways such as peroxisome proliferator-activated receptors (PPAR) signaling and pyruvate metabolism. Hub genes had potential regulatory relationships with a variety of miRNAs, transcription factors and small molecule drugs, and had high diagnostic efficacy. Immune infiltration analysis revealed that 13 immune cells were altered in DKD, and hub genes exhibited significant correlations with a variety of immune cells. Through clustering analysis, DKD patients could be classified into 3 immune subtypes and 2 lipid metabolism subtypes, respectively. The tubular expression of hub genes in DKD was further verified by other external datasets, and immunohistochemistry (IHC) staining showed that except ACACB, the other 4 hub genes (LPL, AHR, ME1 and ALOX5) exhibited the same results as the bioinformatics analysis. Our study identified several key lipid metabolism-related genes (LPL, AHR, ME1 and ALOX5) that might be involved in tubular injury in DKD, which provide new insights and perspectives for exploring the pathogenesis and potential therapeutic targets of DKD.

Dietary carbohydrate to lipid ratio affects growth, reproductive performance and health of female yellow catfish (Pelteobagrus fulvidragrus): a lipidomics analysis

This study aimed to examine the impact of dietary carbohydrate to lipid (CHO/L) ratio on the growth, reproductive, and offspring performance of broodstock yellow catfish, and to elucidate the metabolic differences between mothers and offspring using lipidomics. Five isonitrogenous and isoenergetic diets with varying CHO/L ratios (0.65, 1.44, 2.11, 3.13, and 5.36) were fed to three groups of 35 female broodfish in a pond-cage culture system. After an eight-week feeding trial, the dietary CHO/L ratio had a significant impact on the growth and reproductive performance of female yellow catfish. The weight gain ratio (WGR) and specific growth rate (SGR) in the CHO/L0.65 and CHO/L2.11 groups were significantly higher than those in the CHO/L5.36 group (P < 0.05). The fertilization and hatching rates were the highest when the dietary CHO/L ratio was 0.65 and 2.11, respectively. When the dietary CHO/L ratio was 3.13 and 5.36, the plasma contents of testosterone (T) was significantly lower than those of other groups (P = 0.013), and the plasma vitellogenin (VTG) content was the lowest when the CHO/L ratio was 5.36. The plasma contents of estradiol (E2) significantly decreased with increasing dietary CHO/L ratio (PL = 0.012). Lipidomic analysis revealed that the ovary primarily consisted of five subclasses in terms of lipid composition, namely triglyceride, fatty acyl, sterol, glycerophospholipid, and sphingolipid; however, sphingolipids were not detected in the larvae. The relative expression levels of the ovarian lipid metabolism-related genes sterol regulatory element binding protein 1 (srebp1), acetyl-coa carboxylase (acc), delta (12)-oleate desaturase (fad2), and elongation of very long chain fatty acids protein 5 (elvol5) significantly increased with increasing dietary CHO/L ratio (P < 0.05). The relative expression levels of lipid metabolism-related genes srebp 1, peroxisome proliferator activated receptor α (pparα), carnitine palmitoyl transferase 1 isoform (cpt), adipose triglyceride lipase (atgl), fad2, and elvol5 in offspring larvae were initially increased and then decreased with increasing dietary CHO/L ratios until reaching a maximum at a ratio of 2.11 (P < 0.05). In conclusion, based on the broken-line regression of the dietary CHO/L ratio and egg diameter, the optimal dietary CHO/L ratio was 1.91 for broodfish yellow catfish. A high-CHO/L ratio diet results in increased lipogenesis and hepatic lipid accumulation in maternal organisms, leading to impaired reproductive performance and reduced offspring quality.

Fucoxanthin Mitigates High-Fat-Induced Lipid Deposition and Insulin Resistance in Skeletal Muscle through Inhibiting PKM1 Activity.

Glucose and lipid metabolism dysregulation in skeletal muscle contributes to the development of metabolic disorders. The efficacy of fucoxanthin in alleviating lipid metabolic disorders in skeletal muscle remains poorly understood. In this study, we systematically investigated the impact of fucoxanthin on mitigating lipid deposition and insulin resistance in skeletal muscle employing palmitic acid-induced lipid deposition in C2C12 cells and ob/ob mice. Fucoxanthin significantly alleviated PA-induced skeletal muscle lipid deposition and insulin resistance. In addition, fucoxanthin prominently upregulated the expression of lipid metabolism-related genes (Pparα and Cpt-1), promoting fatty acid β-oxidation metabolism. Additionally, fucoxanthin significantly increased the expression of Pgc-1α and Tfam, elevated the mtDNA/nDNA ratio, and reduced ROS levels. Further, we identified pyruvate kinase muscle isozyme 1 (PKM1) as a high-affinity protein for fucoxanthin by drug affinity-responsive target stability and LC-MS and confirmed their robust interaction by CETSA, microscale thermophoresis, and circular dichroism. Supplementation with pyruvate, the product of PKM1, significantly attenuated the beneficial effects of fucoxanthin on lipid deposition and insulin resistance. Mechanistically, fucoxanthin reduced glucose glycolysis rate and enhanced mitochondrial biosynthesis and fatty acid β-oxidation through inhibiting PKM1 activity, thereby alleviating lipid metabolic stress. These findings present a novel clinical strategy for treating metabolic diseases using fucoxanthin.

Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease

The mechanisms underlying lipid metabolic disorders in Parkinson's diseases (PD) remain unclear. Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify PD-related modular genes and differentially expressed genes (DEGs). Lipid metabolism-related genes (LMRGs) were extracted from Molecular Signatures Database. Candidate genes were assessed with overlapping modular genes, DEGs, and LMRGs for the purpose of building protein–protein interaction (PPI) networks. Then, biomarkers were generated by machine learning and Backpropagation Neural Network development according to candidate genes. Biomarker-based enrichment and network modulation analyses were executed to investigate related signaling pathways. Following dimensionality reduction clustering and annotation, scRNA-seq was submitted to cellular interactions and trajectory analysis to analyze regulatory mechanisms of critical cells. Finally, qRT-PCR was conducted to confirm the expression of biomarkers in PD patients. Four biomarkers (MSMO1, ELOVL6, AACS, and CERS2) were obtained and highly predictive after analysis mentioned above. Then, OPC, Oli, and Neu cells were the primary expression sites for biomarkers according to scRNA-seq studies. Finally, we confirmed mRNA of MSMO1, ELOVL6 and AACS were downregulated in PD patients comparing with control, while CERS2 was upregulated. In conclusion, MSMO1, ELOVL6, AACS, and CERS2 related to LMRGs could be new biomarkers for diagnosing and treating PD.

The Effects of trans-10, cis-12 Conjugated Linoleic Acid on the Production Performance of Dairy Cows and the Expression and Transcription Regulation of Lipid Metabolism-Related Genes in Bovine Mammary Epithelial Cells.

Dietary fatty acids (FAs) determine the quality of dairy products. The trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) is commonly considered an FA factor leading to milk fat depression syndrome (MFDs) in dairy cow. However, its effect on dairy cow performance and involvement in milk fat metabolism have been insufficiently explored. This study administered 136.17 g/day of rumen-protected CLA (RP-CLA) to dairy cows and found a diminution in milk fat percentage and a trend of increasing milk protein percentage on day 21 postpartum. Lactose content, milk yield, and net energy for lactation were unaffected. In the cell experiments, Oil Red O staining showed a notable increase in lipid droplets. Gene and protein expression analysis showed that 300 μM t10c12-CLA upregulated the expression of CD36, DGAT2, and ADRP, while downregulating the expression of ACACA, FASN, SREBP1, FABP3, FATP3, ACSL4, LPIN1, DGAT1, BTN1A1, XDH, SNAP23, and VAMP4. This provides a possible mechanistic pathway for the contradictory phenomenon of t10c12-CLA reducing milk fat while increasing lipid droplets. Overall, t10c12-CLA, as a long-chain fatty acid, can promote lipid droplet synthesis but may reduce milk fat by inhibiting lipid droplet fusion and secretion, FAs de novo synthesis, and triglyceride biosynthesis.

The Effect of Subclinical Ketosis on the Peripheral Blood Mononuclear Cell Inflammatory Response and Its Crosstalk with Depot-Specific Preadipocyte Function in Dairy Cows.

During the periparturient period, cows undergo heightened energy demands at lactation onset, paired with reduced dry matter intake, leading to negative energy balance (NEB). Excessive lipolysis-driven adipose tissue remodeling, triggered by NEB, significantly contributes to ketosis in periparturient dairy cows. However, the role of peripheral blood mononuclear cells (PBMCs) in the pathogenesis of ketosis and in modulating adipose tissue function remains poorly understood. Here, we investigated how ketosis affects the transcriptional profile and secretome of PBMCs and its influence on preadipocyte function in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Twenty-one postpartum Holstein dairy cows were categorized as either subclinical ketosis (SCK; BHB ≥ 1.0 mM) or control (CON; BHB < 0.8 mM) based on blood beta-hydroxybutyrate (BHB) concentration screening. Blood samples were collected intravenously for the isolation of PBMCs and serum metabolic profiling. Ketosis elevated circulating NEFA and BHB levels but reduced total WBC and neutrophil counts. Isolated PBMCs were evaluated for gene expression and used to produce conditioned media (PBMC-CM), during which PBMCs were stimulated with 10 ng/mL LPS. The overall phenotype of PBMCs was largely consistent between SCK and CON cows, with minimal differences detected in immunomodulatory cytokine expression and PBMC-CM composition following stimulation. Preadipocytes isolated from non-ketotic cows were treated with PBMC-CM to assess the effect of PBMC secretomes on adipose cell function. Preadipocytes treated with SCK PBMC-CM showed reduced lipid accumulation compared to those treated with CON PBMC-CM regardless of the depot. SAT preadipocytes had heightened expression of lipid metabolism-related genes, including DGAT1, LIPE, and FASN, compared to VAT when treated with SCK PBMC-CM. Preadipocytes treated with CM from PBMC stimulated by LPS exhibited upregulation in IL1B and IL6 regardless of the depot or source of PBMCs. Together, these results indicate that although PBMC profiles showed minimal differences, preadipocytes treated with PBMC-CM may be influenced by additional factors, leading to altered preadipocyte function and gene expression that may contribute to adipose cellular dysfunction.

Wnt/Wingless signaling promotes lipid mobilization through signal-induced transcriptional repression

The Wnt/Wingless signaling pathway plays critical roles in metazoan development and energy metabolism, but its role in regulating lipid homeostasis remains not fully understood. Here, we report that the activation of canonical Wnt/Wg signaling promotes lipolysis while concurrently inhibiting lipogenesis and fatty acid β-oxidation in both larval and adult adipocytes, as well as cultured S2R+ cells, in Drosophila. Using RNA-sequencing and CUT&RUN (Cleavage Under Targets & Release Using Nuclease) assays, we identified a set of Wnt target genes responsible for intracellular lipid homeostasis. Notably, active Wnt signaling directly represses the transcription of these genes, resulting in decreased de novo lipogenesis and fatty acid β-oxidation, but increased lipolysis. These changes lead to elevated free fatty acids and reduced triglyceride (TG) accumulation in adipocytes with active Wnt signaling. Conversely, downregulation of Wnt signaling in the fat body promotes TG accumulation in both larval and adult adipocytes. The attenuation of Wnt signaling also increases the expression of specific lipid metabolism-related genes in larval adipocytes, wing discs, and adult intestines. Taken together, these findings suggest that Wnt signaling-induced transcriptional repression plays an important role in regulating lipid homeostasis by enhancing lipolysis while simultaneously suppressing lipogenesis and fatty acid β-oxidation.

Characteristics, clinical significance, and cancer immune interactions of lipid metabolism in prostate cancer.

The relationship between lipid metabolism, immune response, and immunotherapy in prostate cancer (PCa) is closely intertwined, and targeted intervention in lipid metabolism may facilitate the success of anticancer immunotherapy. This research attempted to explore effective immunotherapy for PCa. We obtained RNA sequencing (RNA-seq) data for PCa patients from the UCSC Xena platform. Data analysis of differentially expressed genes (DEGs) was performed using package limma in R. Then, DEGs were subjected to enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The Human Protein Atlas (HPA) database was conducted to validate the protein expression of the up-regulated lipid metabolism related genes (LMRGs) between PCa tissues and normal prostate tissues. And then we identified critical transcription factors (TFs), LMRGs and miRNA by constructing a regulatory network of TF-gene-miRNA. Furthermore, we determined the high and low groups based on the score of lipid metabolism enrichment. The hallmark gene sets were derived from gene expression profiles using the gene set variation analysis (GSVA) R package. Finally, we conducted immune infiltration analysis and drug sensitivity analysis. Immune response and lipid metabolism have undergone significant changes in PCa and paracancerous tissues compared to normal tissues. A total of 21 LMRGs were differentially up-regulated in PCa. The TF-gene-miRNA network showed that PLA2G7, TWIST1, and TRIB3 may be the key genes that elevated lipid metabolism in PCa. The high group had more infiltration of B cell memory, macrophage M0, macrophage M1, and myeloid dendritic cell resting, and the low group had more infiltration of B cell plasma, monocyte, myeloid dendritic cell activated, and mast cell resting. The majority of checkpoint genes exhibited high expression levels in the low group. Lipid metabolism was remarkedly correlated with drug sensitivity. The analysis of lipid metabolism and related genes has revealed a complex regulatory mechanism that has a significant influence on immune response, immunotherapy, and medication guidance for patients with PCa. Prostate cancer (PCa); lipid metabolism; cancer immune; RNA sequencing (RNA-seq).

Effects of dietary astaxanthin on immune status and lipid metabolism in gilthead seabream (Sparus aurata)

Astaxanthin (AX) is a carotenoid known to have one of the highest documented antioxidant capacities and has attracted considerable scientific and commercial interest. The incorporation of AX into aquaculture practices has been associated with improved pigmentation, modulation of the immune and endocrine systems, stress reduction, reproductive efficiency and general fish health. This study describes the effects of dietary AX (0, control, 20, 100 and 500 mg kg−1 AX per kg of diet) for 15 and 30 days on growth performance, immune and antioxidant status, histology and gene expression in gilthead seabream (Sparus aurata). Fish fed diets enriched with 500 mg kg−1 of AX for 15 days decreased in skin mucus peroxidase activity while at 30 days of trial, fish fed a diet supplemented with 20 mg kg−1 AX increased the peroxidase activity in serum. In addition, bactericidal activity against Vibrio harveyi increased in the skin mucus of fish fed any of the AX supplemented diets. Regarding antioxidant activities in the liver, catalase and glutathione reductase were decreased and increased, respectively, in fish fed a diet supplemented with 500 mg kg−1 of AX. Finally, although the expression of up to 21 inflammatory and lipid metabolism-related genes was analysed in visceral adipose tissue, only the expression of the interleukin 6 (il6) gene was up-regulated in fish fed a diet supplemented with 20 mg kg−1 of AX. The present results provide a detailed insight into the potent antioxidant properties of AX and its possible modulatory effects on the immune status and lipid metabolism of seabream, which may be of interest to the aquaculture sector.

Nitrite induces hepatic glucose and lipid metabolism disorders in zebrafish through mitochondrial dysfunction and ERs response

Nitrite, a highly toxic environmental contaminant, induces various physiological toxicities in aquatic animals. Herein, we investigate the in vivo effects of nitrite exposure at concentrations of 0, 0.2, 2, and 20 mg/L on glucose and lipid metabolism in zebrafish. Our results showed that exposure to nitrite induced mitochondrial oxidative stress in zebrafish liver and ZFL cells, which were evidenced by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) as well as decreased mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP). Changes in these oxidative stress markers were accompanied by alterations in the expression levels of genes involved in HIF-1α pathway (hif1α and phd), which subsequently led to the upregulation of glycolysis and gluconeogenesis-related genes (gk, pklr, pdk1, pepck, g6pca, ppp1r3cb, pgm1, gys1 and gys2), resulting in disrupted glucose metabolism. Moreover, nitrite exposure activated ERs (Endoplasmic Reticulum stress) responses through upregulating of genes (atf6, ern1 and xbp1s), leading to increased expression of lipolysis genes (pparα, cpt1aa and atgl) and decreased expression of lipid synthesis genes (srebf1, srebf2, fasn, acaca, scd, hmgcra and hmgcs1). These results were also in consistent with the observed changes in glycogen, lactate and decreased total triglyceride (TG) and total cholesterol (TC) in the liver of zebrafish. Our in vitro results showed that co-treatment with Mito-TEMPO and nitrite attenuated nitrite-induced oxidative stress and improved mitochondrial function, which were indicated by the restorations of ROS, MMP, ATP production, and glucose-related gene expression recovered. Co-treatment of TUDCA and nitrite prevented nitrite-induced ERs response and which was proved by the levels of TG and TC ameliorated as well as the expression levels of lipid metabolism-related genes. In conclusion, our study suggested that nitrite exposure disrupted hepatic glucose and lipid metabolism through mitochondrial dysfunction and ERs responses. These findings contribute to the understanding of the potential hepatotoxicity for aquatic animals in the presence of ambient nitrite.

Identification of lipid metabolism-related gene signature in the bone marrow microenvironment of multiple myelomas through deep analysis of transcriptomic data

Dysregulated lipid metabolism in the bone marrow microenvironment (BMM) plays a vital role in multiple myeloma (MM) development, progression, and drug resistance. However, the exact mechanism by which lipid metabolism impacts the BMM, promotes tumorigenesis, and triggers drug resistance remains to be fully elucidated.By analyzing the bulk sequencing and single-cell sequencing data of MM patients, we identified lipid metabolism-related genes differential expression significantly associated with MM prognosis, referred to as LMRPgenes. Using a cohort of ten machine learning algorithms and 117 combinations, LMRPgenes predictive models were constructed. Further exploration of the effects of the model risk score (RS) on the survival status, immune status of patients with BMM, and response to immunotherapy was conducted. The study also facilitated the identification of personalized therapeutic strategies targeting specified risk categories within patient cohorts.Analysis of the scRNA-seq data revealed increased lipid metabolism-related gene enrichment scores (LMESs) in erythroblasts and progenitor, malignant, and Tprolif cells but decreased LMESs in lymphocytes. LMESs were also strongly correlated with most of the 50 hallmark pathways within these cell populations. An elevated malignant cell ratio and reduced lymphocytes were observed in the high LMES group. Moreover, the LMRPgenes predictive model, consisting of 14 genes, showed great predictive power. The risk score emerged as an independent indicator of poor outcomes. Inverse relationships between the RS and immune status were noted, and a high RS was associated with impaired immunotherapy responses. Drug sensitivity assays indicated the effectiveness of bortezomib, buparlisib, dinaciclib, staurosporine, rapamycin, and MST-312 in the high-RS group, suggesting their potential for treating patients with high-RS values and poor response to immunotherapy. Ultimately, upon verification via qRT-PCR, we observed a significant upregulation of ACBD6 in NDMM group compared to the control group.Our research enhances the knowledge base regarding the association between lipid metabolism-related genes (LMRGs) and the BMM in MM patients, offering substantive insights into the mechanistic effects of the BMM mediated by LMRGs.Graphical abstract

ELOVL5 and VLDLR synergistically affect n-3 PUFA deposition in eggs of different chicken breeds

There was no significant difference in the composition and content of fatty acids in eggs among different breeds initially, but following the supplementation of flaxseed oil, Dwarf Layer were observed to deposit more n-3 polyunsaturated fatty acid (PUFA) in eggs. Currently, there is limited research on the mechanisms underlying the differences in egg composition among different breeds. Therefore, in this study, 150 twenty-four-wk-old hens of each breed, including the Dwarf Layer and White Leghorn, were fed either a basal diet or a diet supplemented with 2.5% flaxseed oil. After 28 d, eggs and liver samples were collected to determine fatty acid composition, and serum, liver, intestine, and follicles were collected for subsequent biochemical, intestinal morphology, and lipid metabolism-related genes expression analysis. Duodenal contents were collected for microbial analysis. The results showed that there was no significant difference in the content and deposition efficiency of total n-3 PUFA in the liver of the 2 breeds, but the content and deposition efficiency of total n-3 PUFA in the egg of Dwarf Layer were significantly higher than those of White Leghorn after feeding flaxseed oil. Flaxseed oil and breeds did not have significant effects on cholesterol (CHO), free fatty acids (NEFA), low-density lipoprotein (LDL), and estrogen (E2) levels. After feeding with flaxseed oil, the villus height and the villus-to-crypt ratio in both breeds were increased and duodenal crypt depth was decreased. The villus-to-crypt ratio (4.78 vs. 3.60) in the duodenum of Dwarf Layer was significantly higher than that in White Leghorn after feeding with flaxseed oil. Flaxseed oil can impact the gut microbiota in the duodenum and reduce the microbiota associated with fatty acid breakdown, such as Romboutsia, Subdolibranulum, Lachnochlostridium, and Clostridium. This may mean that less ALA can be decomposed and more ALA can be absorbed into the body. Additionally, after feeding flaxseed oil, the mRNA levels of elongation enzymes 5 (ELOVL5), fatty acid desaturase 1 (FADS1), and fatty acid transporter 1 (FATP1) in the liver of Dwarf Layer were significantly higher than those in White Leghorn, while the mRNA levels of peroxisome proliferator-activated receptor alpha (PPAR), carnitine palmitoyl transferase 1 (CPT1), Acyl CoA oxidase 1 (ACOX1), and Acyl-CoA synthetase (ACSL) were significantly lower than those in White Leghorn. The mRNA level of FABP1 in the duodenum of Dwarf Layer was significantly higher than that of White Leghorn, while the mRNA level of FATP1 was significantly lower than that of White Leghorn. The protein levels of ELOVL5 in the liver of Dwarf Layer and very low-density lipoprotein receptor (VLDLR) in the follicles were significantly higher than those of White Leghorn. In summary, after feeding flaxseed oil, the higher ratio of villus height to crypt depth in Dwarf Layer allows more α-linolenic acid (ALA) to be absorbed into the body. The higher mRNA expression of FADS1, ELOVL5, and FATP1, as well as the higher protein expression of ELOVL5 in the liver of Dwarf Layer enhance the conversion of ALA into DHA. The higher protein expression of VLDLR in follicles of Dwarf Layer allows more n-3 PUFA to deposit in the follicles. These combined factors contribute to the Dwarf Layer's ability to deposit higher levels of n-3 PUFA in eggs, as well as improving the deposition efficiency of n-3 PUFA.

Positive effects and mechanism of mulberry leaf extract on alleviating fatty liver hemorrhagic syndrome in laying hens

This experiment was conducted to investigate the effects of mulberry leaf extract (MLE) on alleviating fatty liver hemorrhagic syndrome (FLHS) in laying hens. The 576 Jing Fen laying hens of 56 weeks of age with good health and similar weights (1.76 ± 0.17 kg) were randomly divided into 6 groups, with 8 replicates in each group and 12 chickens in each replicate. The experiment lasted 56 d. The control group was fed a corn-soybean meal diet. The FLHS group was fed a high energy-low protein (HELP) diet, and the other four experimental groups were fed HELP diets supplemented with 0.04, 0.40, 0.80, and 1.20% MLE, respectively. The results showed that HELP treatment significantly induced liver injury, which indicated that the FLHS model was successfully established. MLE supplementation could alleviate the FLHS by reducing the liver index, abdominal fat percentage, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in the serum (P < 0.05), and subsequently increase the egg production rate (P < 0.05). The laying hens fed 0.8% MLE exhibited the greatest production performance (P < 0.05) and could improve serum lipid levels. In addition, the genes associated with fatty acid synthesis (ACC, HMGR and SREBP-1C) were downregulated (P < 0.05), and genes related to fatty acid oxidation (CPT1A, AMPK, and ATGL) were found to be upregulated (P < 0.05). Supplementation with 1.2% MLE significantly reduced the relative abundance of Firmicutes and Desulfurized Bacillus (P < 0.05) and significantly increased the relative abundance of Fecal Bacillus (P < 0.05). In conclusion, MLE may regulate the mRNA expression of lipid metabolism-related genes through the AMPK signaling pathway and improve cecal microbiota balance and serum lipid levels to alleviate FLHS in laying hens and subsequently improve egg production performance.

Expression characteristics of lipid metabolism-related genes and correlative immune infiltration landscape in acute myocardial infarction

Lipid metabolism is an important part of the heart's energy supply. The expression pattern and molecular mechanism of lipid metabolism-related genes (LMRGs) in acute myocardial infarction (AMI) are still unclear, and the link between lipid metabolism and immunity is far from being elucidated. In this study, 23 Common differentially expressed LMRGs were discovered in the AMI-related mRNA microarray datasets GSE61144 and GSE60993. These genes were mainly related to “leukotriene production involved in inflammatory response”, “lipoxygenase pathway”, “metabolic pathways”, and “regulation of lipolysis in adipocytes” pathways. 12 LMRGs (ACSL1, ADCY4, ALOX5, ALOX5AP, CCL5, CEBPB, CEBPD, CREB5, GAB2, PISD, RARRES3, and ZNF467) were significantly differentially expressed in the validation dataset GSE62646 with their AUC > 0.7 except for ALOX5AP (AUC = 0.699). Immune infiltration analysis and Pearson correlation analysis explored the immune characteristics of AMI, as well as the relationship between these identified LMRGs and immune response. Lastly, the up-regulation of ACSL1, ALOX5AP, CEBPB, and GAB2 was confirmed in the mouse AMI model. Taken together, LMRGs ACSL1, ALOX5AP, CEBPB, and GAB2 are significantly upregulated in AMI patients' blood, peripheral blood of AMI mice, myocardial tissue of AMI mice, and therefore might be new potential biomarkers for AMI.

Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

4-tert-Butylphenol impairs the liver by inducing excess liver lipid accumulation via disrupting the lipid metabolism pathway in zebrafish

Endocrine disrupting chemicals (EDCs) can disrupt normal endocrine function by interfering with the synthesis and release of hormones, causing adverse reactions to development, immunity, nerves, and reproduction. 4-tert-Butylphenol (4-t-BP) is disruptive to early zebrafish development, but its effects on zebrafish liver are unknown. In this study, the adverse effects of 4-t-BP on the liver were investigated using zebrafish as a model organism. 4-t-BP inhibited liver development in zebrafish embryos and induced liver damage in adult zebrafish. Even if F1 was not directly exposed to 4-t-BP, its growth and development were inhibited. 4-t-BP can lead to an increase in lipid accumulation, total cholesterol and triglycerides contents, and the activities of alanine transaminase and aspartate aminotransferase in zebrafish embryos and adult zebrafish livers, and also cause an acceleration of glucose metabolism in zebrafish embryos. In addition, qRT-PCR showed that 4-t-BP induced the changes in the expressions of liver development-, steroid and unsaturated fatty acid biosynthesis-, and glycerolipid and arachidonic acid metabolism-related genes in zebrafish embryos and inflammatory factors-, antioxidant enzymes- and lipid metabolism-related genes in adult zebrafish livers. Transcriptome sequencing of embryos showed that 4-t-BP altered the expressions of lipid metabolism pathways such as steroid and unsaturated fatty acid biosynthesis, glycerolipid, and arachidonic acid metabolism pathways. Therefore, 4-t-BP may be external stimuli that cause oxidative stress, inflammation, and lipid accumulation in zebrafish liver, resulting in tissue damage and dysfunction in zebrafish liver.

Effects of emulsifiers on lipid metabolism and performance of yellow-feathered broilers

BackgroundReducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed.ResultsThe results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05).ConclusionsThese results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens.

Nanopore sequencing demonstrates the roles of spermatozoal DNA N6-methyladenine in mediating transgenerational lipid metabolism disorder induced by excessive folate consumpton

Increased consumption of folic acid is prevalent due to its beneficial effects, but growing evidence emphasizes the side effects pointing to excessive dietary folate intake. The effects of excessive paternal folic acid consumption on offspring and its transgenerational inheritance mechanism have not been elucidated. We hypothesize that excessive folic acid consumption will alter sperm DNA N6-methyladenine (6mA) and 5-methylcytosine (5mC) methylation and heritably influence offspring metabolic homeostasis. Here, we fed roosters either folic acid-control or folic acid-excess diet throughout life. Paternal chronic folic acid excessive supplementation increased hepatic lipogenesis and lipid accumulation but reduced lipolysis both in the roosters and their offspring, which was further confirmed to be induced by one-carbon metabolism inhibition and gene expression alteration associated with the Peroxisome proliferator-activated receptor pathway. Based on the spermatozoal genome-wide DNA methylome identified by Nanopore sequencing, multi-omics association analysis of spermatozoal and hepatic DNA methylome, transcriptome, and metabolome suggested that differential spermatozoal DNA 6mA and 5mC methylation could be involved in regulating lipid metabolism-related gene expression in offspring chickens. This model suggests that sperm DNA N6-methyladenine and 5-methylcytosine methylation were involved in epigenetic transmission and that paternal dietary excess folic acid leads to hepatic lipid accumulation in offspring.

Targeted next-generation sequencing panel to investigate antiplatelet adverse reactions in acute coronary syndrome patients undergoing percutaneous coronary intervention with stenting

Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that pharmacological intervention based on a limited number of high-evidence variants (primarily CYP2C19*2 and *3) can reduce the incidence of major adverse cardiovascular events (MACEs), ADRs still occur at variable rates (10.1 % in our case) despite personalized therapy.This study aimed to identify novel genetic variants associated with the endpoint of MACEs 12 months after PCI by designing and analyzing a targeted gene panel. We sequenced 244 ACS-PCI-stent patients (109 with event and 135 without event) and 99 controls without structural cardiovascular disease and performed an association analysis to search for unexpected genetic variants.No single nucleotide polymorphisms reached genomic significance after correction, but three novel variants, including ABCA1 (rs2472434), KLB (rs17618244), and ZNF335 (rs3827066), may play a role in MACEs in ACS patients. These genetic variants are involved in regulating high-density lipoprotein levels and cholesterol deposition, and as they are regulatory variants, they may affect the expression of nearby lipid metabolism-related genes. Our findings suggest new targets (both at the gene and pathway levels) that may increase susceptibility to MACEs, but further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process.

APOA1 mRNA and serum APOA1 protein as diagnostic and prognostic biomarkers in gastric cancer.

Gastric cancer (GC) remains a formidable challenge in oncology, ranking as a leading cause of cancer mortality globally. This underscores an urgent need for innovative prognostic markers that can revolutionize patient management and outcomes. Recent insights into cancer biology have spotlighted the profound influence of lipid metabolism alterations on tumorigenesis, tumor progression, and the tumor microenvironment. These alterations not only fuel cancer cell growth and proliferation but also play a strategic role in evading immune surveillance and promoting metastasis. The intricate web of lipid metabolism in cancer cells, characterized by deregulated uptake, synthesis, and oxidation of fatty acids (FAs), opens new avenues for targeted therapeutic interventions and prognostic evaluations. Specifically, this study zeroes in on apolipoprotein A-I (APOA1), a key player in lipid metabolism, to unearth its prognostic value in GC. By delving into the role of lipid metabolism-related genes, particularly APOA1, we aim to unveil their potential as groundbreaking biomarkers for GC prognosis. This endeavor not only aims to enhance our understanding of the molecular underpinnings of GC but also to spearhead the development of lipid metabolism-based strategies for improved diagnostic, prognostic, and therapeutic outcomes. Transcriptomic and clinical data from GC patients and healthy individuals were sourced from The Cancer Genome Atlas (TCGA) database, a comprehensive project that molecularly characterizes over 20,000 primary cancer and matched normal samples across 33 cancer types. Significantly differentially expressed lipid metabolism-related genes were identified using the "limma" package in R. Prognostic genes were selected via univariate Cox regression analysis. Differential gene enrichment analysis was performed using Metascape (http://www.metascape.org). The Human Protein Atlas (HPA, https://www.proteinatlas.org) provided information on APOA1 protein expression in GC and healthy tissues. Immune cell infiltration was analyzed using the CIBERSORT algorithm (http://cibersort.stanford.edu). Significant differences in lipid metabolism-related gene expression were observed between GC and normal tissues, closely linked to FA metabolism, oxidoreductase activity, and sphingolipid metabolism. APOA1 emerged as a potential prognostic biomarker by intersecting prognostic and differentially expressed lipid metabolism genes. Immunohistochemical analysis confirmed APOA1 downregulation in GC. The receiver operating characteristic (ROC) analysis demonstrated its predictive value, with the area under the curve (AUC) being 0.64 [95% confidence interval (CI): 0.52-0.76]. APOA1 expression correlated with immune cell infiltrations. Clinical serum APOA1 results revealed lower levels in GC patients (1.38 vs. 1.26; P<0.05), associated with poor prognosis (hazard ratio =1.50; P<0.001) and clinical characteristics. ROC analysis of serum APOA1 demonstrated good diagnostic ability (AUC: 0.63, 95% CI: 0.61-0.65). Serum APOA1 levels significantly increased after treatment. This study highlights lipid metabolism reprogramming in GC and identifies APOA1 as a potential diagnostic and prognostic biomarker, suggesting its clinical utility in managing GC.