Hepatology articles within Nature Communications

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  • Article
    | Open Access

    Non-alcoholic fatty liver (NAFLD) disease causes degeneration of the liver, affects about 25% of people globally, and has no approved treatment. Here, the authors show that the therapeutic siRNA-driven silencing of MCJ in the liver is an effective and safe treatment for NAFLD in multiple mouse models.

    • Lucía Barbier-Torres
    • , Karen A. Fortner
    •  & Mercedes Rincón

  • Article
    | Open Access

    The shortage of viable donated livers limits patient access to liver transplantation. Here the authors report the use of normothermic machine perfusion to help identify viable organs from livers discarded based on current clinical criteria, which are then transplanted to recipients in a single-arm clinical trial.

    • Hynek Mergental
    • , Richard W. Laing
    •  & Darius F. Mirza

  • Article
    | Open Access

    Here the authors perform a gain-of-function screen and identify CDKN2C as a host factor for HBV replication, inducing cell cycle arrest and expression of HBV transcription enhancers. CDKN2C expression correlates with disease progression suggesting a potential role in HBV-induced liver disease.

    • Carla Eller
    • , Laura Heydmann
    •  & Thomas F. Baumert

  • Article
    | Open Access

    Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications with limited treatment options. Here the authors show that dysregulation of bile acids increases risk for PTB in pregnant women while restoring bile acid homeostasis delays or prevents PTB in the mouse models.

    • Sangmin You
    • , Ai-Min Cui
    •  & Ruitang Deng

  • Article
    | Open Access

    The molecular mechanisms that drive irreversible acute liver failure remain poorly characterized. Here, the authors show that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage during acute liver injury by blocking restorative neutrophil driven inflammation.

    • Abhishek Chauhan
    • , Lozan Sheriff
    •  & Patricia F. Lalor

  • Article
    | Open Access

    Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Here, the authors use 1H-MRS methodology to show hepatic SFA fraction is a measure of DNL and specifically may hamper hepatic insulin sensitivity.

    • Kay H. M. Roumans
    • , Lucas Lindeboom
    •  & Vera B. Schrauwen-Hinderling

  • Article
    | Open Access

    FXR agonists have been investigated for the treatment of non-alcoholic steatohepatitis and liver fibrosis but the clinical efficacy is not optimal. Here the authors show that enhanced FXR SUMOylation in activated hepatic stellate cells reduces FXR signaling and that this can be rescued by SUMOylation inhibitors.

    • Jiyu Zhou
    • , Shuang Cui
    •  & Haiping Hao

  • Article
    | Open Access

    Activated hepatic stellate cells of putative mesodermal origin orchestrate scarring during injury. Here, the authors define a discrete morphologically plastic lineage of embryonic mesothelial-derived scar-orchestrating cells, through a distinct quiescent adult precursor, defined and paradoxically inhibited by WT1.

    • Timothy James Kendall
    • , Catherine Mary Duff
    •  & Nicholas Dixon Hastie

  • Article
    | Open Access

    BTLA is established as a negative regulator of natural killer T (NKT) cell function, and share its ligand HVEM with CD160. Here the authors show, by analyzing NKT activation in CD160-deficient mice or with BTLA blockade, that CD160 synergizes with BTLA to negatively regulate NKT cells during hepatic injury.

    • Tae-Jin Kim
    • , Gayoung Park
    •  & Kyung-Mi Lee

  • Article
    | Open Access

    Alcoholic hepatitis, a common cause of liver failure, lacks effective treatment. Here, the authors show altered hepatic HNF4a isoform expression and hypermethylation of its target genes in patients. HNF4a dysregulation is improved in vitro by TGFb or PPARg modulation suggesting potential therapeutic avenues.

    • Josepmaria Argemi
    • , Maria U. Latasa
    •  & Ramon Bataller

  • Article
    | Open Access

    Development of cirrhosis in individuals with non-alcoholic fatty liver disease can predict mortality. Here the authors used a unique twin and family cohort to identify a gut microbiome-derived 16sRNA signature that can detect cirrhosis in individuals with non-alcoholic fatty liver disease.

    • Cyrielle Caussy
    • , Anupriya Tripathi
    •  & Rohit Loomba

  • Article
    | Open Access

    Obesity increases the risk of hepatocellular carcinoma (HCC) especially in men. Here the authors find a potential mechanistic explanation by showing that, in mice, obesity-induced STAT3 cooperates with the androgen receptor to activate the mTORC pathway through up regulation of CCRK, resulting in hepatic steatosis worsening and HCC development via metabolic and immune reprogramming.

    • Hanyong Sun
    • , Weiqin Yang
    •  & Alfred S. L. Cheng

  • Article
    | Open Access

    No effective pharmacological treatments exist for nonalcoholic fatty liver disease (NAFLD). Here, the authors show that serotonin concentration in the portal blood is increased in nine human subjects and in mice fed a high-fat diet, and that local serotonin signaling ablation, either genetically or with an antagonist, prevents hepatic steatosis in mice.

    • Wonsuk Choi
    • , Jun Namkung
    •  & Hail Kim

  • Article
    | Open Access

    CD8 T cells can protect the liver from viral infection, but can also result in severe liver damage and organ failure. Here, the authors develop a mouse model reflecting fulminant CD8 T cell mediated viral hepatitis, which occurs in a perforin-dependent manner that is protected by the use of perforin inhibitors.

    • M. Welz
    • , S. Eickhoff
    •  & W. Kastenmüller

  • Article
    | Open Access

    The development of single cell RNA sequencing technologies has been instrumental in advancing our understanding of tissue biology. Here, MacParland et al. performed single cell RNA sequencing of human liver samples, and identify distinct populations of intrahepatic macrophages that may play specific roles in liver disease.

    • Sonya A. MacParland
    • , Jeff C. Liu
    •  & Ian D. McGilvray

  • Article
    | Open Access

    Spatial mapping of genomic programs in tissue cells is an important step in the understanding of organ function and disease. Here, the authors provide a spatially resolved epigenomic and transcriptomic map of human liver and show porto-central gradients in metabolic and morphogen networks and transcription factor binding sites as a basis to better understand liver regeneration and function.

    • Mario Brosch
    • , Kathrin Kattler
    •  & Jochen Hampe

  • Article
    | Open Access

    The LXR-SREBP1c pathway promotes hepatic lipogenesis that is deregualted in fatty liver disease. Here the authors show that the long noncoding RNA Blnc1 contributes to the development of obesity-driven steatosis by enabling SREBP1c trascriptional activity in response to LXR activation.

    • Xu-Yun Zhao
    • , Xuelian Xiong
    •  & Jiandie D. Lin

  • Article
    | Open Access

    Insulin promotes lipogenesis but, on the other hand, insulin resistance is associated with increased lipogenesis in the liver. Here the authors show that Snail1 is upregulated by insulin and inhibits lipogenesis by repressing Fasn expression but insulin-mediated Snail1 upregulation is impaired during obesity and insulin resistance.

    • Yan Liu
    • , Lin Jiang
    •  & Liangyou Rui

  • Article
    | Open Access

    FXR plays an important role in bile acid homeostasis by transcriptionally modulating several enterohepatic genes, including intestinal FGF19, that repress hepatic bile acid synthesis. Here the authors show that postprandial FGF19 regulates FXR transcriptional activity via its action on the tyrosine kinase Src, which phosphorylates FXR.

    • Sangwon Byun
    • , Dong-Hyun Kim
    •  & Jongsook Kim Kemper

  • Article
    | Open Access

    Steatosis is characterized by initial accumulation of lipids, followed by inflammation and ultimately fibrosis. Here the authors show that the histone demethylase Plant Homeodomain Finger 2 protects liver form steatosis progression by acting as a co-activator of ChREBP, thus, favouring lipid accumulation without inflammation.

    • Julien Bricambert
    • , Marie-Clotilde Alves-Guerra
    •  & Renaud Dentin

  • Article
    | Open Access

    Senescence has been suggested as causing biliary cholangiopathies but how this is regulated is unclear. Here, the authors generate a mouse model of biliary senescence by deleting Mdm2 in bile ducts and show that inhibiting TGFβ limits senescence-dependent aggravation of cholangiopathies.

    • Sofia Ferreira-Gonzalez
    • , Wei-Yu Lu
    •  & Stuart J. Forbes

  • Article
    | Open Access

    How tumor cells control metastatic niche formation is not fully understood. Here, the authors show in a lung metastatic niche, high-metastatic hepatocellular carcinoma cells secrete exosomal miR-1247-3p that leads to activation of β1-integrin-NF-κBsignalling, converting fibroblasts to cancer-associated fibroblasts.

    • Tian Fang
    • , Hongwei Lv
    •  & Hongyang Wang

  • Article
    | Open Access

    Acetaminophen-induced liver injury is one of the most common causes of liver failure and has to be treated within hours of the overdose. Here Barbier-Torres et al. show that targeting MCJ, a mitochondrial negative regulator, even 24 h after the overdose protects liver from acetaminophen-induced damage.

    • Lucía Barbier-Torres
    • , Paula Iruzubieta
    •  & María Luz Martínez-Chantar

  • Article
    | Open Access

    Organ regeneration by transplantation of ESC/iPSC-derived tissues is a promising but still challenging approach. Here Lin et al. show that liver damage caused by a chemical insult induces not only fibrosis but also Lgr5+ cell expansion that can be further promoted by treatment with HGF/R-spondin1.

    • Yuan Lin
    • , Zhe-Ping Fang
    •  & Wei-Jie Zhou

  • Article
    | Open Access

    The transcription factor ERG is key to endothelial lineage specification and vascular homeostasis. Here the authors show that ERG balances TGFβ signalling through the SMAD1 and SMAD3 pathways, protecting the endothelium from endothelial-to-mesenchymal transition and consequent liver fibrosis in mice via a SMAD3-dependent mechanism.

    • Neil P. Dufton
    • , Claire R. Peghaire
    •  & Anna M. Randi

  • Article
    | Open Access

    Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy.

    • Rachel J. Perry
    • , Liang Peng
    •  & Gerald I. Shulman

  • Article
    | Open Access

    The accumulation of senescent cells is thought to contribute to the age-associated decline in tissue function. Here, the authors identify HSP90 inhibitors as a new class of senolytic compounds in an in vitro screening and show that administration of a HSP90 inhibitor reduces age-related symptoms in progeroid mice.

    • Heike Fuhrmann-Stroissnigg
    • , Yuan Yuan Ling
    •  & Paul D. Robbins

  • Article
    | Open Access

    Hepcidin controls systemic iron levels by inhibiting intestinal iron absorption and iron recycling. Here, Pasricha et al. demonstrate that the hepcidin-chromatin locus displays HDAC3-mediated reversible epigenetic modifications during both erythropoiesis and iron deficiency.

    • Sant-Rayn Pasricha
    • , Pei Jin Lim
    •  & Hal Drakesmith

  • Article
    | Open Access

    Fatty liver is one of the major features of metabolic syndrome and its development is associated with deregulation of systemic lipid and glucose homeostasis. Here Heidenreich et al. show that retinol saturase is implicated in hepatic lipid metabolism by regulating the activity of the transcription factor ChREBP.

    • Steffi Heidenreich
    • , Nicole Witte
    •  & Michael Schupp

  • Article
    | Open Access

    Lambda interferons (IFNL) are involved in the immune response to viral infection. Here the authors show that zinc can interfere with IFNL signalling, and that in HCV patients the rs12979860 polymorphism regulates blood zinc levels and, subsequently, the hepatic immune response.

    • Scott A. Read
    • , Kate S. O’Connor
    •  & Golo Ahlenstiel

  • Article
    | Open Access

    p53 regulates lipid metabolism and fatty acid oxidation, and its inactivation promotes diet-induced liver steatosis. Here Porteiroet al. show that p53 deficiency leads to compensatory p63 upregulation, which, in turn, triggers endoplasmic reticulum stress through IKKβ activation, fatty acid synthesis and lipid accumulation.

    • Begoña Porteiro
    • , Marcos F. Fondevila
    •  & Ruben Nogueiras

  • Article
    | Open Access

    GCN5 inhibits hepatic gluconeogenesis through acetylation of PGC-1α. Here the authors show that GCN5 also activates hepatic gluconeogenesis by acetylating histone H3K9, and that the affinity of GCN5 for its different substrates is regulated via phosphorylation at S275 by PKA in a CITED2-dependent manner.

    • Mashito Sakai
    • , Tomoko Tujimura-Hayakawa
    •  & Michihiro Matsumoto

  • Article
    | Open Access

    Hepatocytes are highly specialized cells and their fate is determined by their position in the liver as either periportal or perivenous hepatocytes. Here, Pu et al. show through genetic lineage tracing for Mfsd2 that periportal hepatocytes proliferate and reprogram into pericentral hepatocytes during liver regeneration and injury.

    • Wenjuan Pu
    • , Hui Zhang
    •  & Bin Zhou

  • Article
    | Open Access

    Activation of hepatic stellate cells is a critical event in the development of fibrosis, which is driven by TGF-beta and inhibited by IFN-gamma. Here Wu et al. show that the RNA binding protein CUGBP1 is increased by TGF-beta signalling and promotes IFN-gamma mRNA degradation.

    • Xingxin Wu
    • , Xudong Wu
    •  & Qiang Xu

  • Article
    | Open Access

    Type 2 diabetes and obesity are associated with increased hepatic gluconeogenesis and lipogenesis, known as selective insulin resistance. Here Kubota et al. explain selective insulin resistance in the liver with the zonal distribution and selective insulin-mediated regulation of Irs1 and Irs2.

    • Naoto Kubota
    • , Tetsuya Kubota
    •  & Takashi Kadowaki

  • Article
    | Open Access

    RNA-binding proteins (RBP) are an emerging group of post-translational regulators. Here the authors show that the RBP vigilin regulates translation of mRNA encoding for proatherogenic proteins—apoB, apoC-III and fibronectin—representing a potential therapeutic target in cardiovascular diseases.

    • Mehrpouya B. Mobin
    • , Stefanie Gerstberger
    •  & Markus Stoffel

  • Article
    | Open Access

    Chronic Hepatitis C infection is associated with a broad spectrum of liver pathologies, ranging from inflammation to fibrosis and liver cancer. Here Thabet et al. identified a polymorphism in the gene MBOAT7 that is associated with increased hepatic inflammation and higher risk of fibrosis development and progression.

    • Khaled Thabet
    • , Anastasia Asimakopoulos
    •  & Rosanna Santaro

  • Article
    | Open Access

    Application of carbon nanotubes as drug delivery carriers is stalled by uncertainties over their distribution and toxicity in vivo. Here, the authors use animal models to show that, while the bulk of nanotubes is renally cleared, a fraction can be eliminated through an alternative hepatobiliary pathway.

    • Simone Alidori
    • , Robert L. Bowman
    •  & Michael R. McDevitt

  • Article
    | Open Access

    Liver fibrosis is a pathogenic driver of many liver diseases, so understanding its regulation might open the door to new therapies. Here the authors perform a screen for miRNA candidates and identify that miR-378 inhibits liver fibrosis in mice by interfering with Hedgehog signalling in hepatic stellate cells.

    • Jeongeun Hyun
    • , Sihyung Wang
    •  & Youngmi Jung

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