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Anthropogenic and extreme climate disasters cause ecological changes in natural rivers and lakes, increasing the risk of starvation in yellowcheek (Elopichthys bambusa). Therefore, the impact of starvation on the metabolism and wild population of yellowcheek should be explored. In this study, we used transcriptome sequencing technology to analyze the effects of short (8 d) and long-term (28 d) starvation on the liver transcriptome, growth, and serum indicators of yellowcheek. Our results showed that short-term starvation significantly reduced the visceral weight and viscera index of yellowcheek. Long-term starvation significantly reduced the body weight and Fulton’s condition factor, and it maintained significant reductions in visceral weight and viscera index. These results indicate that glycogen is the preferred energy source, rather than muscle protein, under starvation. Short-term starvation limited N-glycan and fatty acid biosynthesis, fatty acid elongation in the endoplasmic reticulum in the liver, and upregulated fatty acid degradation. However, long-term starvation alleviated the reduction in N-glycan and fatty acid biosynthesis caused by early starvation, and it significantly reduced fatty acid elongation in the mitochondria, as well as fatty acid degradation. These results provide important experiment information for assessing the starvation levels and nutritional status of wild yellowcheek.

BACKGROUND The trans-fat containing AMLN (amylin liver non-alcoholic steatohepatitis, NASH) diet has been extensively validated in C57BL/6J mice with or without the Lepob/Lepob (ob/ob) mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH. Due to a recent ban on trans-fats as food additive, there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice. AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat. METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat (Primex shortening) substituted by equivalent amounts of palm oil [Gubra amylin NASH, (GAN) diet] for 8, 12 and 16 wk. C57BL/6J mice were fed the same diets for 28 wk. AMLN and GAN diets had similar caloric content (40% fat kcal), fructose (22%) and cholesterol (2%) level. RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance. Biopsy-confirmed steatosis, lobular inflammation, hepatocyte ballooning, fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet. C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets. CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsy-confirmed NASH in ob/ob and C57BL/6J mice, making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.

Anti-lipopolysaccharide (LPS) antibody administration has the potential benefits of neutralizing and consequently controlling rumen-derived LPS during subacute ruminal acidosis. Four Holstein bulls were used in this crossover study with a 2-week wash-out period. Anti-LPS antibody (0 or 4 g) was administered once daily for 14 days. Significantly lower ruminal LPS and higher 1-h mean ruminal pH were identified in the 4 g group. However, blood metabolites, acute-phase proteins, cytokines, and hepatic transcriptomes were not different between the two groups. Therefore, anti-LPS antibody administration mitigated ruminal LPS release and pH depression without accompanying responses in acute-phase inflammation or hepatic transcriptomic expression.

Background: Hua-Feng-Dan is a patent Chinese medicine for stroke recovery and is effective against Parkinson’s disease models with modulatory effects on gut microbiota, but its effects on hepatic gene expression are unknown. This study used RNA-Seq to profile hepatic gene expression by Hua-Feng-Dan and its “Guide Drug” Yaomu. Methods: Mice received orally Hua-Feng-Dan 1.2 g/kg, Yaomu 0.1-0.3 g/kg, or vehicle for 7 days. Liver pathology was examined, and total RNA was isolated for RNA-Seq. The bioinformatics, including GO and KEGG pathway enrichment analysis, two-dimensional clustering, Ingenuity Pathways Analysis (IPA), and Illumina BaseSpace Correlation Engine were used to analyze differentially expressed genes (DEGs). qPCR was performed to verify selected genes. Results: Hua-Feng-Dan and Yaomu did not produce liver toxicity as evidenced by histopathology and serum ALT and AST. GO Enrichment revealed Hua-Feng-Dan affected lipid homeostasis, protein folding and cell adhesion. KEGG showed activated cholesterol metabolism, bile secretion and PPAR signaling pathways. DEGs were identified by DESeq2 with p < 0.05 compared to controls. Hua-Feng-Dan produced 806 DEGs, Yaomu-0.1 had 235, and Yaomu-0.3 had 92 DEGs. qPCR on selected genes largely verified RNA-Seq results. IPA upstream regulator analysis revealed activation of MAPK and adaptive responses. Yaomu-0.1 had similar effects, but Yaomu-0.3 had little effects. Hua-Feng-Dan-induced DEGs were highly correlated with the GEO database of chemical-induced adaptive transcriptome changes in the liver. Conclusion: Hua-Feng-Dan at clinical dose did not produce liver pathological changes but induced metabolic and signaling pathway activations. Low dose of its Guide Drug Yaomu produced similar changes to a lesser extent, but high dose of Yaomu had little effects. The effects of Hua-Feng-Dan on liver transcriptome changes may produce adaptive responses to program the liver to produce beneficial or detrimental (over-dosed) pharmacological effects. Keywords:RNA-Seq; Hua-Feng-Dan; Yaomu; Liver transcriptome; Bioinformatics; GEO database correlation.

Bisphenol A (BPA) is an industrial plasticizer widely found in consumer products, and exposure to BPA during early development has been associated with the prevalence of various cardiometabolic diseases including obesity, metabolic syndrome, type 2 diabetes, and cardiovascular diseases. To elucidate the molecular perturbations underlying the connection of low-dose prenatal BPA exposure to cardiometabolic diseases, we conducted a multi-dimensional systems biology study assessing the liver transcriptome, gut microbial community, and diverse metabolic phenotypes in both male and female mouse offspring exposed to 5μg/kg/day BPA during gestation. Prenatal exposure to low-dose BPA not only significantly affected liver genes involved in oxidative phosphorylation, PPAR signaling and fatty acid metabolism, but also affected the gut microbial composition in an age- and sex-dependent manner. Bacteria such as those belonging to the S24-7 and Lachnospiraceae families were correlated with offspring phenotypes, differentially expressed liver metabolic genes such as Acadl and Dgat1, and key drivers identified in our gene network modeling such as Malat1 and Apoa2. This multiomics study provides insight into the relationship between gut bacteria and host liver genes that could contribute to cardiometabolic disease risks upon low-dose BPA exposure.

Microcystin-LR (MC-LR) is a potent hepatotoxin for which a substantial gap in knowledge persists regarding the underlying molecular mechanisms of liver toxicity and injury. Although long non-coding RNAs (lncRNAs) have been extensively studied in model organisms, our knowledge concerning the role of lncRNAs in liver injury is limited. Given that lncRNAs show low levels of sequence conservation, their role becomes even more unclear in non-model organisms without an annotated genome, like whitefish (Coregonus lavaretus). The objective of this study was to discover and profile aberrantly expressed polyadenylated lncRNAs that are involved in MC-LR-induced liver injury in whitefish. Using RNA sequencing (RNA-Seq) data, we de novo assembled a high-quality whitefish liver transcriptome. This enabled us to find 94 differentially expressed (DE) putative evolutionary conserved lncRNAs, such as MALAT1, HOTTIP, HOTAIR or HULC, and 4429 DE putative novel whitefish lncRNAs, which differed from annotated protein-coding transcripts (PCTs) in terms of minimum free energy, guanine-cytosine (GC) base-pair content and length. Additionally, we identified DE non-coding transcripts that might be 3&prime, autonomous untranslated regions (3&prime, UTRs) of mRNAs. We found both evolutionary conserved lncRNAs as well as novel whitefish lncRNAs that could serve as biomarkers of liver injury.

Background In order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin). Results During the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group. Conclusions Our results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.

Fish oil oxidation can produce harmful substances, but the specific effects of oxidized fish oil on liver function in the hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ Epinephelus lanceolatus) are not yet clear. In the present study, hybrid grouper was fed diets containing 0, 3, 6, or 9% oxidized fish oil (referred to as the control, L, M, and H groups respectively) for 65 days to investigate its effects on liver physiology. Oxidized fish oil significantly decreased protein content in liver (P

The factors that affect residual feed intake (RFI) of two chicken breeds (Ross as commercial and Isfahan as Iranian local breed with low and high RFI, respectively) were examined. We sequenced their liver transcriptomes using RNA-Seq while focusing on the identification of important candidate genes, which might influence RFI and growth rate. The differential gene expression analysis revealed that 121 and 279 known genes were significantly up- and down-regulated in the local breed, respectively. QTL enrichment analysis revealed that 63 down-regulated genes in the local breed were enriched in the QTL regions related to feed efficiency traits. Moreover, the functional enrichment analysis showed that the down-regulated genes in the native chickens were mainly involved in the different metabolic processes, such as carboxylic acid metabolic process and response to stress. The Differentially Expressed Genes explored between the chickens of the two breeds led to the identification of some important candidate genes for further breed improvement programmes, including RSAD2, IL15, LIPI, EGR1 and DUSP16. These findings will be a useful resource for the biological investigations of RFI-related genes in Isfahan local chickens and may provide some clues for understanding the molecular genetic mechanisms in other chicken breeds.highlights A global view of transcriptome differences in the liver tissues of commercial and local chicken breeds with different RFI values is obtained. This investigation will contribute to the improvement of chicken genome annotation through the identification of novel transcripts and novel gene. Some important candidate genes related to RFI is obtained.

Simple Summary Swine inflammation and necrosis syndrome (SINS) is a newly identified syndrome associated with inflammatory and necrotic signs in different body parts of suckling piglets, weaners, and fatteners. While the proven inflammatory basis of the disease and the development of signs in even newborns indicate a primarily endogenous etiology, the mechanisms underlying SINS development are largely unknown. In this study, the hypothesis was tested that SINS is indirectly triggered by the translocation of gut-derived microbial components into the liver, thereby causing derangements of liver metabolism, by comparing the hepatic transcriptome and plasma metabolome of SINS-affected and unaffected piglets. Apart from demonstrating that hepatic inflammation occurs in SINS-affected piglets, the study clearly shows for the first time that several metabolic derangements are induced in SINS-affected piglets that may contribute to the clinical and histopathological signs of SINS. Abstract Swine Inflammation and Necrosis Syndrome can lead to severe clinical signs, especially in tails, ears, teats, and claws in pigs. Clinical and histopathological findings in newborn piglets with intact epidermis indicate a primarily endogenous etiology, and microbial-associated molecular patterns (MAMPs), such as lipopolysaccharide (LPS) are assumed to play a central role in the development of the syndrome. We hypothesized that swine inflammation and necrosis syndrome (SINS) is indirectly triggered by gut-derived MAMPs entering the circulatory system via the liver and thereby causing derangements on liver metabolism. To test this hypothesis, metabolomes, candidate genes of the liver and liver transcriptomes of 6 piglets with high-grade clinical signs of SINS (SINS high) were examined and compared with 6 piglets without significant signs of SINS (SINS low). Several hepatic pro-inflammatory genes and genes involved in stress response were induced in piglets of the SINS high group. The most striking finding from hepatic transcript profiling and bioinformatic enrichment was that the most enriched biological processes associated with the approximately 220 genes induced in the liver of the SINS high group were exclusively related to metabolic pathways, such as fatty acid metabolic process. Within the genes (≈390) repressed in the liver of the SINS high group, enriched pathways were ribosome biogenesis, RNA processing, RNA splicing, spliceosome, and RNA transport. The transcriptomic findings were supported by the results of the metabolome analyses. These results provide the first evidence for the induction of an inflammatory process in the liver of piglets suffering from SINS, accompanied by lipid metabolic derangement.

Background Dependence on marine natural resources threatens the sustainability of Atlantic salmon aquaculture. In the present study, Atlantic salmon fed for 14 weeks with an experimental diet based on animal by-products and vegetable oil (ABP) exhibited reduced growth performance compared with others fed a fish meal/fish oil based experimental diet (MAR) and a plant protein/vegetable oil-based experimental diet (VEG). To characterize the molecular changes underlying the differences in growth performance, we conducted a 44 K microarray study of the liver transcriptome of the three dietary groups. Results The microarray experiment identified 122 differentially expressed features (Rank Products, PFP

Obesity, the excessive accumulation of lipids in the body, is closely associated with many prevalent human disorders. Continued efforts to identify plant extracts that exhibit anti-obesity effects have drawn much attention. This study investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity activity and how PTE may affect liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet–induced obese mouse model to determine the effects of PTE on lipid accumulation. Next-generation sequencing analysis of liver gene expression and gut microbiota profiles following PTE treatment were conducted to elucidate possible mechanisms. We found that treatment of fully differentiated 3T3-L1 adipocytes with PTE inhibited lipid accumulation in the cells through reducing lipid formation and triglyceride content and by increasing lipase activity. No cytotoxicity was observed from the PTE treatment. After 5 weeks of treatment with PTE, the increased body weight, elevated serum triglyceride content, and liver steatosis in the high-fat diet–induced obese mice were each reduced. Liver transcriptomic analysis revealed that expression of genes involved in lipid and cholesterol metabolism was significantly altered. The low-grade chronic inflammation of obesity caused by a high-fat diet was also decreased after PTE treatment. In addition, treatment with PTE improved the relatively low Bacteroidetes/Firmicutes ratio in the gut of high-fat diet–fed mice through enrichment of the Proteobacteria population and reduction of the Deferribacteres population. In conclusion, treatment with PTE inhibited lipid accumulation by inducing the expression of the master transcription factor PPARα, attenuated the low-grade chronic inflammation of obesity, and also altered gut microbiota profiles. These results indicate that PTE has the potential to be developed into an anti-obesity food supplement and therapy. Abbreviations: Abcg5: ATP-binding cassette subfamily G member 5; ALT: alanine aminotransferase; AMPK: adenosine monophosphate-activated protein kinase; AST: aspartate aminotransferase; B/F: Bacteroidetes to Firmicutes [ratio]; C/EBPα: CCAAT/enhancer-binding protein alpha; CR: creatinine; Cyp51: cytochrome P450 family 51; DMEM: Dulbecco’s modified Eagle’s medium; Fabp5: fatty acid-binding protein 5; FBS: fetal bovine serum; Fdps: farnesyl diphosphate synthase; Glc: Glucose; HFD: high-fat diet; GO: gene ontology; HPRT: hypoxanthine guanine phosphoribosyl transferase; IBMS: 3-isobutyl-1-methylxanthine; Idi1: isopentenyl-diphosphate delta isomerase 1; IL-1β: interleukin-1-beta; Lpin1: phosphatidic acid phosphohydrolase; LPS: lipopolysaccharide; Mvd: mevalonate diphosphate decarboxylase; ND: normal diet; OTU: operational taxonomic units; Pcsk9: proprotein convertase subtilisin/kexin 9; Pctp: phosphatidylcholine transfer protein; PPARα: peroxisome proliferator-activated receptor alpha; PPARγ: peroxisome proliferator-activated receptor gamma; PTE: Polygala tenuifolia extract; Saa1: serum amyloid A1; SD: standard deviation; SEM: standard error of the mean; Serpina12: serpin family member 12; Sqle: squalene monooxygenase; SREBP1C: sterol regulatory element-binding protein 1C; TCHO: total cholesterol; TG: triglyceride