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Background/Aims: Accumulating evidences have demonstrated that long noncoding RNAs (lncRNA) play important roles in hepatic lipid metabolism in mammals. However, no systematic screening of the potential lncRNAs in the livers of laying hens has been performed, and few studies have been reported concerning the effects of the lncRNAs on lipid metabolism in the livers of chickens during egg-laying period. The purpose of this study was to compare the difference in lncRNA expression in the livers of pre-laying and peak-laying hens at the age of 20 and 30 weeks old by transcriptome sequencing and to investigate the interaction networks among lncRNAs, mRNAs and miRNAs. Moreover, the regulatory mechanism and biological function of lncLTR, a significantly differentially expressed lncRNA in the liver between pre- and peak-laying hens, was explored in vitro and in vivo. Methods: Bioinformatics analyses were conducted to identify the differentially expressed (DE) lncRNAs between the two groups of hens. The target genes of the DE lncRNA were predicated for further functional enrichment. An integrated analysis was performed among the DE lncRNA datasets, DE mRNAs and DE miRNA datasets obtained from the same samples to predict the interaction relationship. In addition, in vivo and in vitro trials were carried out to determine the expression regulation of lncLTR, and polymorphism association analysis was conducted to detect the biological role of lncLTR. Results: A total of 124 DE lncRNAs with a P-value ≤ 0.05 were identified. Among them, 44 lncRNAs including 30 known and 14 novel lncRNAs were significant differentially expressed (SDE) with FDR ≤ 0.05. Thirty-two lncRNAs were upregulated and 12 were downregulated in peak-laying group compared with pre-laying group. The functional enrichment results revealed that target genes of some lncRNAs are involved in the lipid metabolism process. Integrated analysis suggested that some of the genes involved in lipid metabolism might be regulated by both the lncRNA and the miRNA. In addition, an upregulated lncRNA, designated lncLTR, was demonstrated to be induced by estrogen via ERβ signaling. The c242. G>A SNP in lncLTR was significantly associated with chicken carcass weight, evisceration weight, semi-evisceration weight, head weight, double-wing weight, claw weight traits, and blood biochemical index, especially for the blood triglyceride content. Conclusion: A series of lncRNAs associated with lipid metabolism in the livers of chickens were identified by transcriptome sequencing and functional analysis, providing a valuable data resource for further studies on chicken hepatic metabolism activities. LncLTR was regulated by estrogen via ERβ signaling and associated with chicken carcass trait and blood triglyceride content. [ABSTRACT FROM AUTHOR]

Background/Aims: Malaria is the most deadly parasitic infection in the world, resulting in damage to various organs, including the liver, of the infected organism; however, the mechanism causing this damage in the liver remains unclear. Liver fibrosis, a major characteristic of liver diseases, occurs in response to liver injury and is regulated by a complex network of signaling pathways. Hedgehog (Hh) signaling orchestrates a number of hepatic responses including hepatic fibrogenesis. Therefore, we investigated whether Hh signaling influenced the liver's response to malarial infection. Methods: Eight-week-old male C57BL/6 mice inoculated with blood containing Plasmodium berghei ANKA (PbA)-infected erythrocytes were sacrificed when the level of parasitemia in the blood reached 10% or 30%, and the livers were collected for biochemical analysis. Liver responses to PbA infection were examined by hematoxylin and eosin staining, real-time polymerase chain reaction, immunohistochemistry and western blot. Results: Severe hepatic injury, such as ballooned hepatocytes, sinusoidal dilatation, and infiltrated leukocytes, was evident in the livers of the malaria-infected mice. Hypoxia was also induced in 30% parasitemia group. With the accumulation of Kupffer cells, inflammation markers, TNF-&$945;, interleukin-1β, and chemokine (C-X-C motif) ligand 1, were significantly upregulated in the infected group compared with the control group. Expression of fibrotic markers, including transforming growth factor-β, a-smooth muscle actin (a-SMA), collagen 1a1, thymosin β4, and vimentin, were significantly higher in the infected groups than in the control group. With increased collagen deposition, hepatic stellate cells expressing a-SMA accumulated in the liver of the PbA-infected mice, whereas those cells were rarely detected in the livers of the control mice. The levels of Hh signaling and Yes-associated protein (YAP), two key regulators for hepatic fibrogenesis, were significantly elevated in the infected groups compared with the control group. Treatment of mice with Hh inhibitor, GDC-0449, reduced hepatic inflammation and fibrogenesis with Hh suppression in PbA-infected mice. Conclusion: Our results demonstrate that HSCs are activated in and Hh and YAP signaling are associated with this process, contributing to increased hepatic fibrosis in malaria-infected livers. [ABSTRACT FROM AUTHOR]

Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA) rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS) production in the ZDF rat brain compared to the liver, while nitric oxide (NO) production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA) control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-α confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]