Liver Transcriptome Analysis Research Articles

Transcriptome analysis of liver lipid metabolism disorders of the turbot Scophthalmus maximus in response to low salinity stress

The turbot Scophthalmus maximus is one of the most economically important fish harvested from the coastal areas of northern China. Low salinity stress is an important obstacle to the development of the turbot industry. However, the underlying molecular mechanisms response to low salinity stress in turbot have not been fully investigated, especially in metabolism. In the present study, liver transcriptome analysis was performed to identify genes and pathways involved in the responses of turbot to different salinity conditions (0 psu fresh water [FW] and 30 psu sea water [SW]). Related changes in blood biochemical parameters were also assessed. A total of 826 differentially expressed genes (DEGs) were identified, of which 245 were down-regulated while 581 were up-regulated. KEGG pathway analysis indicated that 11 pathways were enriched, involving lipid metabolism, the endocrine system, endocrine and metabolic diseases, signaling molecules and interactions, the digestive system, and signal transduction. Further analysis showed that a significant portion of the pathways were related to energy metabolism, especially lipid metabolism. The verified DEGs involved in lipid metabolism basically showed a significant downward trend under low salinity stress, including acetyl-CoA carboxylase alpha (ACC), carnitine O-palmitoyltransferase 1 (CPT-1), cholesterol 7-alpha-monooxygenase (CYP7A1), liver X receptor alpha (LXRα), apolipoprotein A-IV (ApoAIV), fatty acid binding protein (FABP), and sterol regulatory element-binding protein 1 (SREBP-1). Almost all of these genes were related to LXRα. Moreover, the physiological results showed that serum cholesterol content remained stable in both the SW and FW groups, while the serum triglyceride content significantly decreased with time in the FW group. These results show that low salinity stress inhibits lipid absorption and synthesis via the LXRα signaling pathway and can result in liver lipid metabolism disorders in turbot. These findings provide new insights into the molecular mechanism of turbot in response to low salinity stress and turbot culture under low salinity. It is possible that lipid metabolites in blood can be selected as phenotype traits for breeding under low- salinity conditions, although further verification is needed.

ILRUN, a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice.

Single-nucleotide polymorphisms near the ILRUN (inflammation and lipid regulator with ubiquitin-associated-like and NBR1 [next to BRCA1 gene 1 protein]-like domains) gene are genome-wide significantly associated with plasma lipid traits and coronary artery disease (CAD), but the biological basis of this association is unknown. To investigate the role of ILRUN in plasma lipid and lipoprotein metabolism. ILRUN encodes a protein that contains a ubiquitin-associated-like domain, suggesting that it may interact with ubiquitinylated proteins. We generated mice globally deficient for Ilrun and found they had significantly lower plasma cholesterol levels resulting from reduced liver lipoprotein production. Liver transcriptome analysis uncovered altered transcription of genes downstream of lipid-related transcription factors, particularly PPARα (peroxisome proliferator-activated receptor alpha), and livers from Ilrun-deficient mice had increased PPARα protein. Human ILRUN was shown to bind to ubiquitinylated proteins including PPARα, and the ubiquitin-associated-like domain of ILRUN was found to be required for its interaction with PPARα. These findings establish ILRUN as a novel regulator of lipid metabolism that promotes hepatic lipoprotein production. Our results also provide functional evidence that ILRUN may be the casual gene underlying the observed genetic associations with plasma lipids at 6p21 in human.

Comparative transcriptome analysis of livers from three strains of Chinese swamp eels

Comparative transcriptome analysis of livers from three strains of Chinese swamp eels

Transcriptome analysis of liver provides insight into metabolic and translation changes under hypoxia and reoxygenation stress in silver sillago (Sillago sihama)

Hypoxia can lead to adverse effects on growth, reproduction, behavioral activities and survival in fish, and is one of the most critical factors in the aquatic environment. The liver is an important target organ for reducing toxin accumulation and hypoxia in fish. In this study, silver sillago (Sillago sihama) was exposed to normoxia (dissolved oxygen, DO = 8.0 mg/L), hypoxia for 1 h (hypoxia 1 h, DO = 1.5 mg/L), hypoxia for 4 h (hypoxia 4 h, DO = 1.5 mg/L) and reoxygenation for 4 h after hypoxia 4 h (reoxygenation 4 h, DO = 8.0 mg/L). Results showed that the expression of 506, 1721, and 1230 differentially expressed genes (DEGs) (|log2(fold change) > 1.0| and padj < 0.05) were identified at hypoxia 1 h, hypoxia 4 h, and reoxygenation 4 h in the liver, respectively. The enrichment analysis showed that the DEGs were significantly enriched in metabolic and translation changes pathways, including mapk signaling pathway, p53 signaling pathway, fatty acid metabolism, protein export, ribosome biogenesis in eukaryotes. The DEGs of 17 genes validated the RNA-seq results by quantitative real-time PCR (qRT-PCR). This study provides a comprehensive understanding of the transcriptional changes that occur in different hypoxia and insights into the mechanisms of hypoxia adaptation of the liver in S. sihama.

Diet Composition Affects Liver and Mammary Tissue Transcriptome in Primiparous Holstein Dairy Cows.

Simple SummaryCorn stover (CS) diets are still adopted by small dairy farms in China. Compared with mixed forage (MF) diets, feeding CS diet affects milk composition, digestibility, feed intake, ruminal fermentation, and lactation performance. Mammary gland and liver are two of the most important organs for lactation in cows. However, research related to the effect of CS diet on the metabolism of liver and mammary tissues of dairy cows is limited. Overall evaluation of the biological response of liver and mammary tissues of dairy cows to changes in CS diet compared with MF diet is essential. Thus, the objective of the present study was to evaluate the overall adaptation of liver and mammary tissue to a CS diet in mid-lactation primiparous dairy cows. Modest effect on the transcriptome of the liver and mammary tissue by the CS diet was observed. The analysis of the genes affected by CS indicated mammary gland responding to lower level of linoleate from the diet (lower in CS vs. MF) by activating the associated biosynthesis metabolism while the liver adaptively activated potassium transport to compensate for a lower K ingestion. The results of this study may facilitate the development of better feeding and management strategies and the increase of profitability of dairy farms.The objective of the present study was to evaluate the overall adaptations of liver and mammary tissue to a corn stover (CS) compared to a mixed forage (MF) diet in mid-lactation primiparous dairy cows. Twenty-four primiparous lactating Holstein cows were randomly allocated to 2 groups receiving either an alfalfa forage diet (MF, F:C = 60:40) with Chinese wildrye, alfalfa hay and corn silage as forage source or a corn stover forage diet (CS, F:C = 40:60). A subgroup of cows (n = 5/diet) was used for analysis of liver and mammary transcriptome using a 4 × 44K Bovine Agilent microarray chip. The results of functional annotation analysis showed that in liver CS vs. MF inhibited pathways related to lipid metabolism while induced the activity of the potassium channel. In mammary tissue, fatty acid metabolism was activated in CS vs. MF. In conclusion, the analysis of genes affected by CS vs. MF indicated mammary gland responding to lower level of linoleate from the diet (lower in CS vs. MF) by activating the associated biosynthesis metabolic pathway while the liver adaptively activated potassium transport to compensate for a lower K ingestion.

Humanized GPRC6AKGKY is a gain-of-function polymorphism in mice

GPRC6A is proposed to regulate energy metabolism in mice, but in humans a KGKY polymorphism in the third intracellular loop (ICL3) is proposed to result in intracellular retention and loss-of-function. To test physiological importance of this human polymorphism in vivo, we performed targeted genomic humanization of mice by using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9) system to replace the RKLP sequence in the ICL3 of the GPRC6A mouse gene with the uniquely human KGKY sequence to create Gprc6a-KGKY-knockin mice. Knock-in of a human KGKY sequence resulted in a reduction in basal blood glucose levels and increased circulating serum insulin and FGF-21 concentrations. Gprc6a-KGKY-knockin mice demonstrated improved glucose tolerance, despite impaired insulin sensitivity and enhanced pyruvate-mediated gluconeogenesis. Liver transcriptome analysis of Gprc6a-KGKY-knockin mice identified alterations in glucose, glycogen and fat metabolism pathways. Thus, the uniquely human GPRC6A-KGKY variant appears to be a gain-of-function polymorphism that positively regulates energy metabolism in mice.

Transcriptomic analysis across liver diseases reveals disease-modulating activation of constitutive androstane receptor in cholestasis.

Background & AimsLiver diseases are caused by many factors, such as genetics, nutrition, and viruses. Therefore, it is important to delineate transcriptomic changes that occur in various liver diseases.MethodsWe performed high-throughput sequencing of mouse livers with diverse types of injuries, including cholestasis, diet-induced steatosis, and partial hepatectomy. Comparative analysis of liver transcriptome from mice and human samples of viral infections (HBV and HCV), alcoholic hepatitis (AH), non-alcoholic steatohepatitis (NASH), and biliary atresia revealed distinct and overlapping gene profiles associated with liver diseases. We hypothesised that discrete molecular signatures could be utilised to assess therapeutic outcomes. We focused on cholestasis to test and validate the hypothesis using pharmacological approaches.ResultsHere, we report significant overlap in the expression of inflammatory and proliferation-related genes across liver diseases. However, cholestatic livers were unique and displayed robust induction of genes involved in drug metabolism. Consistently, we found that constitutive androstane receptor (CAR) activation is crucial for the induction of the drug metabolic gene programme in cholestasis. When challenged, cholestatic mice were protected against zoxazolamine-induced paralysis and acetaminophen-induced hepatotoxicity. These protective effects were diminished upon inhibition of CAR activity. Further, drug metabolic genes were also induced in the livers from a subset of biliary atresia patients, but not in HBV and HCV infections, AH, or NASH. We also found a higher expression of CYP2B6, a CAR target, in the livers of biliary atresia patients, underscoring the clinical importance of our findings.ConclusionsComparative transcriptome analysis of different liver disorders revealed specific induction of phase I and II metabolic genes in cholestasis. Our results demonstrate that CAR activation may lead to variations in drug metabolism and clinical outcomes in biliary atresia.Lay summaryTranscriptomic analysis of diverse liver diseases revealed alterations in common and distinct pathways. Specifically, in cholestasis, we found that detoxification genes and their activity are increased. Thus, cholestatic patients may have an unintended consequence on drug metabolism and not only have a beneficial effect against liver toxicity, but also may require adjustments to their therapeutic dosage.

Transcriptome analysis of Takifugu obscurus liver in response to acute retene exposure

Retene (1-methyl-7-isopropyl-phenanthrene, RET) is an alkyl polycyclic aromatic hydrocarbon (PAH) with environmental risk to aquatic animals. Takifugu obscurus is a migratory fish species with high economic and ecological value. To assess the toxic effects of RET on molecular metabolism, juvenile T. obscurus in this study were acutely exposed to 44.30 µg/L of RET for four days. The transcriptome profiles of livers were compared between RET treatment group and the control, and the results revealed that 1,897 genes were significantly differentially expressed (DEGs) after exposure to RET, which enriched 17 KEGG pathways. Among these, glycerolipid metabolism, glycerophospholipid metabolism, insulin signaling pathway, and FOXO signaling pathways were significantly activated. Further exploration indicated that RET exposure disrupted glucose metabolism, stimulated insulin metabolism, and activated cell proliferation genes. Overall, these findings help explain the molecular mechanisms underlying RET toxicity, and may offer evidence to support T. obscurus protection.

Caloric restriction attenuates C57BL/6\u2009J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure

BackgroundCaloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.ResultsMale C57BL/6 J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m3) of PM2.5. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.ConclusionThese novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.

Prevention of Hyperuricemia by Clerodendrum trichotomum Leaf Extract in Potassium Oxonate-Induced Mice.

Clerodendrum trichotomum is a folk medicine exhibiting anti-hypertension, anti-arthritis, and anti-rheumatism properties. However, little is known about whether the material might prevent hyperuricemia and associated inflammation. In this study, we explored whether C. trichotomum leaf extract (CTE) prevented hyperuricemia induced by potassium oxonate (PO) in mice. CTE (400 mg/kg body weight) significantly reduced the serum uric acid (UA), blood urea nitrogen (BUN), and serum creatinine levels and increased urine UA and creatinine levels. CTE ameliorated PO-induced inflammation and apoptosis by reducing the levels of relevant proteins in kidney tissues. Also, CTE ameliorated both UA-induced inflammatory response in RAW 263.7 cells and UA-induced cytotoxicity in HK-2 cells. In addition, liver transcriptome analysis showed that CTE enriched mainly the genes for mediating positive regulation of MAPK cascade and apoptotic signaling pathways. Together, the results show that CTE effectively prevents hyperuricemia and associated inflammation in PO-induced mice.

Effective microtissue RNA extraction coupled with Smart-seq2 for reproducible and robust spatial transcriptome analysis

Spatial transcriptomics is useful for understanding the molecular organization of a tissue and providing insights into cellular function in a morphological context. In order to obtain reproducible results in spatial transcriptomics, we have to maintain tissue morphology and RNA molecule stability during the image acquisition and biomolecule collection processes. Here, we developed a tissue processing method for robust and reproducible RNA-seq from tissue microdissection samples. In this method, we suppressed RNA degradation in fresh-frozen tissue specimens by dehydration fixation and effectively collected a small amount of RNA molecules from microdissection samples by magnetic beads. We demonstrated the spatial transcriptome analysis of the mouse liver and brain in serial microdissection samples (100 μm in a diameter and 10 μm in thickness) produced by a microdissection punching system. Using our method, we could prevent RNA degradation at room temperature and effectively produce a sequencing library with Smart-seq2. This resulted in reproducible sequence read mapping in exon regions and the detection of more than 2000 genes compared to non-fixed samples in the RNA-seq analysis. Our method would be applied to various transcriptome analyses, providing the information for region specific gene expression in tissue specimens.

Hybrid Rat Diversity Program (HRDP): A rat resource for mapping complex traits

Rats are a major model for studying complex disease mechanisms, behavioral phenotypes, environmental factors, and for drug development and discovery. Inbred rat strains control for genetic background and allow for repeated, reproducible molecular, cellular, and whole animal phenotyping. Genetic susceptibility to disease, sensitivity to environmental elements, and pharmacogenomics are critical components of the concepts of precision medicine. A resource that combines the power of genetic stability within strains, power for genomic mapping strategies, and strength in an animal model that mirrors many human disease traits is the goal of this project. Through the development of the Hybrid Rat Diversity Program (HRDP), a powerful panel of inbred rats with genomic, physiologic, and behavioral phenotype data is beginning to serve as a catalyst for research in many fields. When complete, the HRDP will consist of 96 inbred rat strains to maximize power to detect specific genetic loci associated with complex traits while maximizing the genetic diversity among strains. The 96 strain panel consists of 33 genetically diverse inbred strains and two panels of recombinant inbred panels: FEXL/LEXF (33 strains, Japan) and HXB/BXH (30 strains, Czech Republic). Embryo resuscitation and breeding is well underway at the Medical College of Wisconsin (MCW). Whole genome sequencing for 32 of the 96 strains is complete, having been generated on am Illumina NovaSeq S4 to achieve 30X coverage. Liver and brain transcriptome analysis is underway through PhenoGen ( http://phenogen.ucdenver.edu) at the University of Colorado. Genomic, phenotype, and strain information will be made available through the Hybrid Rat Diversity Panel portal at the Rat Genome Database ( http://rgd.mcw.edu). The HRDP will provide a genetically stable population of rat strains with fully sequenced genomes, transcriptomes for brain and liver, and general phenotypic characterization to be used for systems genetic studies and fine mapping of complex traits.Support or Funding InformationNational Institutes of Health, Office of the Director, R24OD024617

Liver Transcriptomic Reveals Novel Pathways of Empagliflozin Associated With Type 2 Diabetic Rats.

The hypoglycaemic target of empagliflozin (EMP), as a novel inhibitor of sodium-glucose cotransporter (SGLT2), is clear. However, recent studies have shown that EMP also has an important role in lipid metabolism and cardiovascular diseases. The liver plays an important role in the development of type 2 diabetes (T2D), although whether EMP affects liver glucose metabolism is currently not reported. This study was designed to evaluate the effect of EMP on hepatic glucose metabolism in T2D and the underlying mechanism. A model of T2D was established by a high-fat and glucose diet (HFD) combined with streptozotocin (30 mg/kg) in male Wistar rats. Serum samples were collected to measure biochemical indicators, and liver samples were extracted for RNA-seq assay. Quantitative real-time PCR (qPCR) was used to further verify the gene expression levels detected by the RNA-seq assay. The EMP group showed significantly decreased blood glucose, triglyceride, cholesterol, non-esterified fatty acid and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels in serum compared with the type 2 diabetes model (MOD) group. Furthermore, EMP decreased the levels of inflammatory factors IL-1β, IL-6, and IL-8 in the serum compared to the MOD. Liver transcriptome analysis showed EMP affects a large number of upregulated and downregulated genes. Some of these genes are novel and involve in the metal ion binding pathway and the negative regulation of transcription from the RNA polymerase II promoter pathway, which are also closely related to glucolipid metabolism and insulin signaling. Our study provides new knowledge about the mechanism through which SGLT inhibitor can offer beneficial effects in T2D and especially in the hepatic metabolism. These genes found in this study also laid a solid foundation for further research on the new roles and mechanisms of EMP.

Liver transcriptome analysis and cortisol immune-response modulation in lipopolysaccharide-stimulated in channel catfish (Ictalurus punctatus)

Channel catfish (Ictalurus punctatus) is an important aquaculture species in China. In channel catfish, diseases such as haemorrhagic, sepsis and tail-rot disease are all caused by bacteria as general in China. Most of the pathogenic bacteria are Gram-negative bacteria. Liver transcriptome analysis of the co-injection of cortisol and lipopolysaccharide (LPS) was performed in this study. Preliminary evidence from the results suggest that after the emergence of immune stress, cortisol will up-regulate the complement cascade pathway, down-regulate the coagulation cascade pathway, down-regulate the platelet activation pathway, down-regulate antigen presentation pathway, and show complex regulation relationship to inflammatory factors. At 12 h, the number of differential genes regulated by cortisol was about half less than the number of differential genes regulated by LPS. At 24 h, there was no significant difference between the number of differential genes regulated by cortisol and LPS, but the types of differential genes vary widely. KEGG enrichment analysis found that cortisol regulated LPS-stimulated immune responses mainly focus on cytokines, complement and coagulation cascades pathways, antigen presentation pathways, haematopoiesis, and inflammation. It is suggested that there may be some strategic choice in the regulation of immune response by cortisol. These results will help understand the pathogenesis and host defence system in bacterial disease caused by Gram-negative bacteria.

TNF-alpha inhibition ameliorates HDV-induced liver damage in a mouse model of acute severe infection.

Background & AimsHDV infection induces the most severe form of human viral hepatitis. However, the specific reasons for the severity of the disease remain unknown. Recently, we developed an HDV replication mouse model in which, for the first time, liver damage was detected.MethodsHDV and HBV replication-competent genomes and HDV antigens were delivered to mouse hepatocytes using adeno-associated vectors (AAVs). Aminotransferase elevation, liver histopathology, and hepatocyte death were evaluated and the immune infiltrate was characterized. Liver transcriptomic analysis was performed. Mice deficient for different cellular and molecular components of the immune system, as well as depletion and inhibition studies, were employed to elucidate the causes of HDV-mediated liver damage.ResultsAAV-mediated HBV/HDV coinfection caused hepatocyte necrosis and apoptosis. Activated T lymphocytes, natural killer cells, and proinflammatory macrophages accounted for the majority of the inflammatory infiltrate. However, depletion studies and the use of different knockout mice indicated that neither T cells, natural killer cells nor macrophages were necessary for HDV-induced liver damage. Transcriptomic analysis revealed a strong activation of type I and II interferon (IFN) and tumor necrosis factor (TNF)-α pathways in HBV/HDV-coinfected mice. While the absence of IFN signaling had no effect, the use of a TNF-α antagonist resulted in a significant reduction of HDV-associated liver injury. Furthermore, hepatic expression of HDAg resulted in the induction of severe liver damage, which was T cell- and TNF-α-independent.ConclusionsBoth host (TNF-α) and viral (HDV antigens) factors play a relevant role in HDV-induced liver damage. Importantly, pharmacological inhibition of TNF-α may offer an attractive strategy to aid control of HDV-induced acute liver damage.Lay summaryChronic hepatitis delta constitutes the most severe form of viral hepatitis. There is limited data on the mechanism involved in hepatitis delta virus (HDV)-induced liver pathology. Our data indicate that a cytokine (TNF-α) and HDV antigens play a relevant role in HDV-induced liver damage.

Liver transcriptomics highlights interleukin-32 as novel NAFLD-related cytokine and candidate biomarker

ObjectiveEfforts to manage non-alcoholic fatty liver disease (NAFLD) are limited by the incomplete understanding of the pathogenic mechanisms and the absence of accurate non-invasive biomarkers. The aim of this study...

Data set for transcriptome analysis of liver in cattle breeds

Transcriptome analysis using high-throughput next-generation sequencing (HT-NGS) technology provides the capability to understand global gene expression variations through a wide range of tissue samples in domesticated animals. We provide raw and analysed data for transcriptomic analysis of liver tissues from Polish-HF, Polish Red and Hereford cattle breeds, obtained by RNA-seq. High-quality sequencing data have been analysed using our bioinformatics pipeline which consists of FastQC for quality controls, Trimmomatic for trimming, and BWA version 0.7.5-r404 for alignment to the Bos taurus reference genome, SAMtools for SNPs identifications, and differentially expressed genes (DEGs) identification using DEseq and edgeR pipelines after adjustment for false-discovery rate (FDR) with adjusted two-sided p values &lt;0.01 and the trimmed mean of M values (TMM) normalisation method. The data accompanying the published manuscript describing the SNPs and DEGs identification in the bovine liver transcriptome of cattle breeds. Raw FASTq files for the RNA-seq libraries are deposited in the NCBI Sequence Read Archive (SRA) and have been assigned BioProject accession PRJNA312148. Raw and processed RNA-seq data were deposited and made publicly available on the Gene Expression Omnibus (GEO; GSE114233).

Candidate Regulators of Dyslipidemia in Chromosome 1 Substitution Lines Using Liver Co-Expression Profiling Analysis.

Dyslipidemia is a major risk factor for cardiovascular disease. Although many genetic factors have been unveiled, a large fraction of the phenotypic variance still needs further investigation. Chromosome 1 (Chr 1) harbors multiple gene loci that regulate blood lipid levels, and identifying functional genes in these loci has proved challenging. We constructed a mouse population, Chr 1 substitution lines (C1SLs), where only Chr 1 differs from the recipient strain C57BL/6J (B6), while the remaining chromosomes are unchanged. Therefore, any phenotypic variance between C1SLs and B6 can be attributed to the differences in Chr 1. In this study, we assayed plasma lipid and glucose levels in 13 C1SLs and their recipient strain B6. Through weighted gene co-expression network analysis of liver transcriptome and “guilty-by-association” study, eight associated modules of plasma lipid and glucose were identified. Further joint analysis of human genome wide association studies revealed 48 candidate genes. In addition, 38 genes located on Chr 1 were also uncovered, and 13 of which have been functionally validated in mouse models. These results suggest that C1SLs are ideal mouse models to identify functional genes on Chr 1 associated with complex traits, like dyslipidemia, by using gene co-expression network analysis.

Growth, osmoregulatory response, adenine nucleotide contents, and liver transcriptome analysis of steelhead trout (Oncorhynchus mykiss) under different salinity acclimation methods

Chinese researchers have been working salmon mariculture far offshore in the Yellow sea, and steelhead trout is one of the popular Salmonidae. This study was conducted to investigate the effect of different salinity acclimation methods on the growth, osmoregulation, energy balance, and liver transcriptome of steelhead trout (Oncorhynchus mykiss). Fish (initial weight, 394.50 g) were reared for 40 days after undergoing salinity acclimation at three rates: an abrupt increase in salinity from zero to 30 ppt (T30); an abrupt increase in salinity to 14 ppt, followed by a daily increase of six ppt (T6) or two ppt (T2), until reaching 30 ppt; and no salinity exposure (control group, T0). Subsequently, serum was collected to determine osmolality, iron concentration, Na+-K+-ATP (NKA) and Ca2+-Mg2+-ATP (CMA) activity; muscle and gill samples were collected for the determination of adenosine 5′-triphosphate (ATP); liver transcriptome was compared between the T0 and T2 groups. The final weight, specific growth rate, food conversion efficiency, and the ATP content of fish in the T2 group were significantly higher than those in the other groups. However, the serum osmolality, serum ion concentration, and gill NKA and CMA activity in the T2 group was significantly lower than that in the T6 and T30 groups. A total of 53,679 unigenes were produced, and 1438 differently expressed genes were selected by DESeq. Among them, 587 genes were up-regulated, while 581 were down-regulated. These differential genes were mainly related to the function of metabolites and ions transportation, energy metabolism, signal transduction, immune responses, and structural assembly. The results indicate that steelhead trout with a weight of approximately 400 g is suitable for mariculture, and T2 was the best transition method for salinity acclimation.

Dietary inulin decreases circulating ceramides by suppressing neutral sphingomyelinase expression and activity in mice

Elevated circulating levels of ceramides (Cers) are associated with increased risk of cardiometabolic diseases, and Cers may play a causative role in metabolic dysfunction that precedes cardiac events, such as mortality as a result of coronary artery disease. Although the mechanisms involved are likely complex, these associations suggest that lowering circulating Cer levels could be protective against cardiovascular diseases. Conversely, dietary fibers, such as inulin, have been reported to promote cardiovascular and metabolic health. However, the mechanisms involved in these protective processes also are not well understood. We studied the effects of inulin on lipid metabolism with a model of atherosclerosis in LDL receptor-deficient mice using lipidomics and transcriptomics. Plasma and tissues were collected at 10 days and/or 12 weeks after feeding mice an atherogenic diet supplemented with inulin or cellulose (control). Compared with controls, inulin-fed mice displayed a decreased C16:0/C24:0 plasma Cer ratio and lower levels of circulating Cers associated with VLDL and LDL. Liver transcriptomic analysis revealed that Smpd3, a gene that encodes neutral SMase (NSMase), was downregulated by 2-fold in inulin-fed mice. Hepatic NSMase activity was 3-fold lower in inulin-fed mice than in controls. Furthermore, liver redox status and compositions of phosphatidylserine and FFA species, the major factors that determine NSMase activity, were also modified by inulin. Taken together, these results showed that, in mice, inulin can decrease plasma Cer levels through reductions in NSMase expression and activity, suggesting a mechanism by which fiber could reduce cardiometabolic disease risk.