- Design and validation of a histological scoring system for nonalcoholic fatty liver disease
David E Kleiner
Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA
Hepatology 41:1313-21. 2005
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD...
- Mechanisms for insulin resistance: common threads and missing links
Varman T Samuel
Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
Cell 148:852-71. 2012
..cellular changes may converge to promote the accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, a common final pathway leading to impaired insulin signaling and insulin resistance.
- Obesity is associated with macrophage accumulation in adipose tissue
Stuart P Weisberg
Division of Moleuclar Genetics, Department of Pediatrics, Columbia University, New York, New York 10032, USA
J Clin Invest 112:1796-808. 2003
..Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals...
- Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA
Catherine L Jopling
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
Science 309:1577-81. 2005
..MicroRNA 122 (miR-122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating ..
- Mapping the genetic architecture of gene expression in human liver
Eric E Schadt
Rosetta Inpharmatics, Seattle, Washington, United States of America
PLoS Biol 6:e107. 2008
..39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs) in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active ..
- Summaries of Affymetrix GeneChip probe level data
Rafael A Irizarry
Department of Biostatistics, Johns Hopkins University, Baltimore, MD 21205, USA
Nucleic Acids Res 31:e15. 2003
..In particular, improvements in the ability to detect differentially expressed genes are demonstrated...
- Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver
Scott L Friedman
Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York 10029 6574, USA
Physiol Rev 88:125-72. 2008
..The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic ..
- Insulin sensitivity: modulation by nutrients and inflammation
Department of Medicine, Division of Endocrinology and Metabolism, UCSD, La Jolla, California 92093, USA
J Clin Invest 118:2992-3002. 2008
..Overall, we provide our integrative perspective regarding how nutrients and obesity interact to regulate insulin sensitivity...
- A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Science 331:1315-9. 2011
..We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent...
- Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
Science 328:1036-40. 2010
..Our results reveal large interspecies differences in transcriptional regulation and provide insight into regulatory evolution...
- miR-221 overexpression contributes to liver tumorigenesis
Nuclear Organization and Oncogenesis Unit, Institut National de Santé et de Recherche Médicale U579, Institut Pasteur, 75724 Paris Cedex 15, France
Proc Natl Acad Sci U S A 107:264-9. 2010
..miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC...
- The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin
Reuben J Shaw
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
Science 310:1642-6. 2005
..The deletion of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK activity...
- Circulating microRNAs, potential biomarkers for drug-induced liver injury
Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103, USA
Proc Natl Acad Sci U S A 106:4402-7. 2009
Drug-induced liver injury is a frequent side effect of many drugs, constitutes a significant threat to patient health and has an enormous economic impact on health care expenditures...
- The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator
Department of Molecular Biology, Sciences II, University of Geneva, 30, Quai Ernest Ansermet, CH 1211 4, Geneva, Switzerland
Cell 110:251-60. 2002
..While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation...
- Regulation of cellular metabolism by protein lysine acetylation
School of Life Sciences, Fudan University, Shanghai 20032, China
Science 327:1000-4. 2010
..TCA) cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism was found to be acetylated in human liver tissue...
- Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring
Karen A Lillycrop
Development and Cell Biology, University of Southampton, UK
J Nutr 135:1382-6. 2005
..Epigenetic regulation of gene transcription provides a strong candidate mechanism for fetal programming...
- Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma
National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China
Cancer Cell 19:232-43. 2011
..An in-depth analysis of miRNomes in human normal liver, hepatitis liver, and hepatocellular carcinoma (HCC) was carried out in this study...
- Human fatty liver disease: old questions and new insights
Jonathan C Cohen
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
Science 332:1519-23. 2011
Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects one-third of adults and an increasing number of children in developed countries...
- Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes
Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA
Science 313:1137-40. 2006
..resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues...
- Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1
Joseph T Rodgers
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 434:113-8. 2005
..homologue, SIRT1--which modulates ageing in several species--controls the gluconeogenic/glycolytic pathways in liver in response to fasting signals through the transcriptional coactivator PGC-1alpha...
- Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice
Institut Cochin, Universite Paris Descartes, CNRS UMR 8104, Paris, France
J Clin Invest 118:829-38. 2008
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes...
- Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages
Singapore Immunology Network, Agency for Science, Technology and Research A STAR, Immunos Building 3 4, Biopolis, 138648, Singapore
J Exp Med 209:1167-81. 2012
..a first wave of yolk sac (YS)-derived primitive myeloid progenitors that seed the skin before the onset of fetal liver hematopoiesis...
- Nonalcoholic fatty liver disease
Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minn 55905, USA
N Engl J Med 346:1221-31. 2002
- Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance
Daniela M L Tsukumo
Department of Internal Medicine, State University of Campinas, Campinas, Sao Paulo, Brazil
Diabetes 56:1986-98. 2007
..ratio, improved insulin sensitivity, and enhanced insulin-signaling capacity in adipose tissue, muscle, and liver compared with control mice during high-fat feeding...
- Telocytes in liver: electron microscopic and immunofluorescent evidence
Regeneration Lab and Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China Innovative Drug Research Center, Shanghai University, Shanghai, China
J Cell Mol Med 17:1537-42. 2013
Hepatic interstitial cells play a vital role in regulating essential biological processes of the liver. Telocytes (TCs), a novel type of interstitial cells firstly identified by Popescu and his coworkers, have been reported in many ..
- Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases
Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
Hepatology 56:1946-57. 2012
MicroRNAs are fine tuners of diverse biological responses and are expressed in various cell types of the liver. Here we hypothesized that circulating microRNAs (miRNAs) may serve as biomarkers of liver damage and inflammation...
- Autophagy regulates lipid metabolism
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
Nature 458:1131-5. 2009
..components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets...
- The gut microbiota as an environmental factor that regulates fat storage
Center for Genome Sciences and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 101:15718-23. 2004
..Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AY 667702--AY 668946)...
- Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA
Cell Metab 8:301-9. 2008
..Together, these results indicate that these CD11c+ cells are a potential therapeutic target for treatment of obesity-related insulin resistance and type II diabetes...
- Nonalcoholic fatty liver disease: a feature of the metabolic syndrome
Unit of Metabolic Diseases, Department of Internal Medicine and Gastroenterology, University of Bologna, Italy
Diabetes 50:1844-50. 2001
..m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2)...
- The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism
Seung Hoi Koo
Peptide Biology Laboratories, Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, California 92037 1002, USA
Nature 437:1109-11. 2005
..Glucagon enhances glucose output from the liver during fasting by stimulating the transcription of gluconeogenic genes via the cyclic AMP-inducible factor CREB (..
- Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
Simon A Hawley
Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, UK
J Biol 2:28. 2003
..We recently showed that LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta...
- miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 2497, USA
RNA Biol 1:106-13. 2004
These studies show that miR-122, a 22-nucleotide microRNA, is derived from a liver-specific noncoding polyadenylated RNA transcribed from the gene hcr...
- Coordinated transcription of key pathways in the mouse by the circadian clock
The Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA
Cell 109:307-20. 2002
..We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed approximately 650 cycling transcripts and showed that the majority of these were specific ..
- Inflammation and insulin resistance
Steven E Shoelson
Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 116:1793-801. 2006
- Resveratrol improves health and survival of mice on a high-calorie diet
Joseph A Baur
Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Nature 444:337-42. 2006
..These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing...
- Liver regeneration
George K Michalopoulos
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
J Cell Physiol 213:286-300. 2007
b>Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types...
- Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
Nature 473:528-31. 2011
..Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity...
- Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, 66160, USA
Drug Metab Rev 44:88-106. 2012
..For example, acetaminophen overdose is currently the most frequent cause of acute liver failure in the United States and Great Britain...
- Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition
Centre de Recerca en Agrigenòmica, Consorci CSIC IRTA UAB UB, Campus UAB, Bellaterra 08193, Spain
BMC Genomics 13:547. 2012
..The main goal of this study was the identification of differentially-expressed genes in the liver of Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition using RNA-..
- Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity
Jeffrey D Browning
Donald W Reynolds Cardiovascular Clinical Research Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9046, USA
Hepatology 40:1387-95. 2004
Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), its pathogenesis and clinical significance remain poorly defined...
- Macrophages, inflammation, and insulin resistance
Jerrold M Olefsky
Department of Medicine, University of California San Diego, La Jolla, CA 92093 0651, USA
Annu Rev Physiol 72:219-46. 2010
Obesity induces an insulin-resistant state in adipose tissue, liver, and muscle and is a strong risk factor for the development of type 2 diabetes mellitus...
- Mechanisms underlying the resistance to diet-induced obesity in germ-free mice
Center for Genome Sciences and Department of Medicine, Washington University School of Medicine, St Louis, MO 63108, USA
Proc Natl Acad Sci U S A 104:979-84. 2007
..Their persistently lean phenotype is associated with increased skeletal muscle and liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream targets involved in fatty acid ..
- Obesity-associated improvements in metabolic profile through expansion of adipose tissue
Ja Young Kim
Department of Cell Biology, Albert Einstein College of Medicine, New York, New York, USA
J Clin Invest 117:2621-37. 2007
..As a consequence, reduced triglyceride levels in the liver and muscle convey improved systemic insulin sensitivity...
- SIRT1 regulates circadian clock gene expression through PER2 deacetylation
Department of Molecular Biology, Sciences III, University of Geneva, 30, Quai Ernest Ansermet, CH 1211 Geneva 4, Switzerland
Cell 134:317-28. 2008
..Given the NAD(+) dependence of SIRT1 deacetylase activity, it is likely that SIRT1 connects cellular metabolism to the circadian core clockwork circuitry...
- MiR-33 contributes to the regulation of cholesterol homeostasis
Katey J Rayner
Department of Medicine, Leon H Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY 10016, USA
Science 328:1570-3. 2010
..Lentiviral delivery of miR-33 to mice represses ABCA1 expression in the liver, reducing circulating HDL levels...
- Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, MO 63110 1093, USA
Hepatology 51:679-89. 2010
Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD)...
- Genome-wide profiling of liver X receptor, retinoid X receptor, and peroxisome proliferator-activated receptor α in mouse liver reveals extensive sharing of binding sites
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
Mol Cell Biol 32:852-67. 2012
The liver X receptors (LXRs) are nuclear receptors that form permissive heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism in the liver...
- Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and
Karen A Lillycrop
Development and Cell Biology, Biomedical Sciences Building, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
Br J Nutr 97:1064-73. 2007
..These findings suggest that induction in the offspring of altered epigenetic regulation of the hepatic GR1(10) promoter, and hence metabolic phenotype, may be due to reduced Dnmt1 expression...
- SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Matthew D Hirschey
Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
Nature 464:121-5. 2010
..Here we report that SIRT3 expression is upregulated during fasting in liver and brown adipose tissues...
- CREB and the CRTC co-activators: sensors for hormonal and metabolic signals
Judith Y Altarejos
Sanford Burnham Medical Research Institute at Lake Nona, 6400 Sanger Road, Orlando, Florida 32827, USA
Nat Rev Mol Cell Biol 12:141-51. 2011
..Following their activation, CREB and CRTCs mediate the effects of fasting and feeding signals on the expression of metabolic programmes in insulin-sensitive tissues...
- MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis
Wei Chih Tsai
Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei, Taiwan
J Clin Invest 122:2884-97. 2012
MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined...
- Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes
Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA
Science 306:457-61. 2004
..Pharmacologic manipulation of this pathway may offer novel opportunities for treating these common diseases...
- Hepcidin and iron homeostasis
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Biochim Biophys Acta 1823:1434-43. 2012
..Hepcidin, ferroportin and their regulators represent potential targets for the diagnosis and treatment of iron disorders and anemias. This article is part of a Special Issue entitled: Cell Biology of Metals...
- The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control
Department of Pharmacology, University of California, Irvine, CA 92697, USA
Cell 134:329-40. 2008
..Finally, using liver-specific SIRT1 mutant mice we show that SIRT1 contributes to circadian control in vivo...
- Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta)
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
Science 292:1728-31. 2001
Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of ..
- PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues
Seung Hee Yoo
Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA
Proc Natl Acad Sci U S A 101:5339-46. 2004
..These results demonstrate that peripheral tissues express self-sustained, rather than damped, circadian oscillations and suggest the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level...
- Functions of autophagy in normal and diseased liver
Mark J Czaja
Department of Medicine Marion Bessin Liver Research Center Albert Einstein College of Medicine Bronx, NY USA
Autophagy 9:1131-58. 2013
..Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic ..
- Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
Varman T Samuel
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
J Biol Chem 279:32345-53. 2004
..fat feeding in rats results specifically in hepatic fat accumulation and provides a model of non-alcoholic fatty liver disease in which to study the mechanism of hepatic insulin resistance...
- Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease
Kerry L Donnelly
Department of Food Science and Nutrition, University of Minnesota, Twin Cities, St Paul, Minnesota, 55108, USA
J Clin Invest 115:1343-51. 2005
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess liver triacylglycerol (TAG), inflammation, and liver damage...
- Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state
Institut Cochin, Universite Paris Descartes, CNRS UMR 8104, Paris, France
J Clin Invest 120:2355-69. 2010
..Surprisingly, here we have found that in mice lacking AMPK in the liver, blood glucose levels were comparable to those in wild-type mice, and the hypoglycemic effect of metformin was ..
- Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene
Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal, Quebec, Canada, H3G 1Y6
Science 283:1544-8. 1999
..The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice...
- Posttranslational mechanisms regulate the mammalian circadian clock
Department of Neurobiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Cell 107:855-67. 2001
We have examined posttranslational regulation of clock proteins in mouse liver in vivo. The mouse PERIOD proteins (mPER1 and mPER2), CLOCK, and BMAL1 undergo robust circadian changes in phosphorylation...
- Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Jeremy S Duffield
Medical Research Council Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
J Clin Invest 115:56-65. 2005
..We investigated macrophage function mechanistically in a reversible model of liver injury in which the injury and recovery phases are distinct...
- Common variants at 30 loci contribute to polygenic dyslipidemia
Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Nat Genet 41:56-65. 2009
..These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia...
- Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 106:15430-5. 2009
..Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues...
- Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites
Noah S Butler
Department of Microbiology, University of Iowa, 3 512 Bowen Science Building, Iowa City, IA 52242, USA
Cell Host Microbe 9:451-62. 2011
..overcome by genetically attenuated parasites (GAP) designed via gene deletion to arrest at defined points during liver-stage development...
- Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development
Institut National de la Sante et de la Recherche Medicale, INSERM, Unite 972, IFR 93, Bicetre Hospital, Kremlin Bicetre, France corrected
Hepatology 51:1754-65. 2010
..could represent an advantageous source of cells for cell therapy approaches as an alternative to orthotopic liver transplantation...
- Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism
The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
Mol Syst Biol 6:401. 2010
..67 versus 0.59). The approach presented can be used to construct other human tissue-specific models, and be applied to other organisms...
- An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tennoudai, Japan
Biochem Biophys Res Commun 236:313-22. 1997
..antioxidant in vivo in both wild type and heterozygous mutant mice, the induction was largely eliminated in the liver and intestine of homozygous nrf2-mutant mice...
- Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4
Lisa Ann Cirillo
Cell and Developmental Biology Program, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
Mol Cell 9:279-89. 2002
The transcription factors HNF3 (FoxA) and GATA-4 are the earliest known to bind the albumin gene enhancer in liver precursor cells in embryos...
- Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans
Kimber L Stanhope
Department of Molecular Biosciences, UCD, Davis, California 95616, USA
J Clin Invest 119:1322-34. 2009
..These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults...
- Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring
Karen A Lillycrop
Development and Cell Biology, Biomedical Sciences Building, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
Br J Nutr 100:278-82. 2008
..These data show for the first time that prenatal nutrition induces differential changes to the methylation of individual CpG dinucleotides in juvenile rats which persist in adults...
- Liver regeneration
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195 7470, USA
Hepatology 43:S45-53. 2006
During liver regeneration after partial hepatectomy, normally quiescent hepatocytes undergo one or two rounds of replication to restore the liver mass by a process of compensatory hyperplasia...
- Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
Catherine S Manno
The Children s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania, 19104, USA
Nat Med 12:342-7. 2006
..IX was accompanied by a transient asymptomatic elevation of liver transaminases that resolved without treatment...
- Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Cell Metab 5:415-25. 2007
..FGF21 is induced directly by PPARalpha in liver in response to fasting and PPARalpha agonists...
- Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study
Christopher D Williams
Gastroenterology and Hepatology Service, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas 78234, USA
Gastroenterology 140:124-31. 2011
Prevalence of nonalcoholic fatty liver disease (NAFLD) has not been well established. The purpose of this study was to prospectively define the prevalence of both NAFLD and nonalcoholic steatohepatitis (NASH).
- Pathogenesis of liver fibrosis
Mount Sinai School of Medicine, New York, New York 10029, USA
Annu Rev Pathol 6:425-56. 2011
b>Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic viral hepatitis and, more recently, from fatty liver disease associated with obesity...
- Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation
Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Zhejiang, China
Ann Surg Oncol 18:1243-50. 2011
..The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression...
- Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
John C Chambers
Epidemiology and Biostatistics, Imperial College London, Norfolk Place, London, UK
Nat Genet 43:1131-8. 2011
Concentrations of liver enzymes in plasma are widely used as indicators of liver disease...
- A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches
Department of Medicine, University of California, La Jolla, CA, USA
Gastroenterology 143:307-20. 2012
..differentiation, proliferation, ROS accumulation, metabolism, insulin signaling, and carcinogenesis in the liver. The biologic functions of JNK are isoform, cell type, and context dependent...
- Sampling variability of liver fibrosis in chronic hepatitis C
Service d Anatomie Pathologique, Hopital Bicetre, Le Kremlin Bicetre, France
Hepatology 38:1449-57. 2003
Fibrosis is a common endpoint of clinical trials in chronic hepatitis C, and liver biopsy remains the gold standard for fibrosis evaluation. However, variability in the distribution of fibrosis within the liver is a potential limitation...
- Molecular mediators of hepatic steatosis and liver injury
Jeffrey D Browning
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75390 9046, USA
J Clin Invest 114:147-52. 2004
..of obesity is insulin resistance, which is strongly associated with the deposition of triglycerides in the liver. Hepatic steatosis can either be a benign, noninflammatory condition that appears to have no adverse sequelae or ..
- Non-alcoholic fatty liver disease: the mist gradually clears
Nimantha Mark Wilfred de Alwis
Liver Group, Institute of Cellular Medicine, Newcastle University, United Kingdom
J Hepatol 48:S104-12. 2008
Non-alcoholic fatty liver disease (NAFLD) is now the commonest liver disorder in the developed world affecting up to a third of individuals...
- Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Cell 119:121-35. 2004
..These data illustrate a central role for PGC-1alpha in the control of energy metabolism but also reveal novel systemic compensatory mechanisms and pathogenic effects of impaired energy homeostasis...
- SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Jay D Horton
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
J Clin Invest 109:1125-31. 2002
- Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis
Arun J Sanyal
Virginia Commonwealth University, Richmond, USA
N Engl J Med 362:1675-85. 2010
Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease.
- Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals
Benjamin R Carone
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Cell 143:1084-96. 2010
- IL-7 licenses activation of human liver intrasinusoidal mucosal-associated invariant T cells
Xin Zi Tang
Viral Hepatitis Laboratory, Singapore Institute for Clinical Sciences, Agency of Science Technology and Research, Singapore 117609
J Immunol 190:3142-52. 2013
..MAIT cells are enriched in the human liver, which is constantly exposed to bacterial products from the intestine...
- Gene expression in fixed tissues and outcome in hepatocellular carcinoma
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
N Engl J Med 359:1995-2004. 2008
..An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue...
- Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C
Service d Hepato Gastroenterologie, Hopital Haut Leveque, C H U Bordeaux, Pessac, France
Gastroenterology 128:343-50. 2005
..elastography (FibroScan; Echosens, Paris, France) is a novel, noninvasive, and rapid bedside method to assess liver fibrosis by measuring liver stiffness...
- Inducible gene targeting in mice
Institute for Genetics, University of Cologne, Germany
Science 269:1427-9. 1995
..Deletion was complete in liver and nearly complete in lymphocytes within a few days, whereas partial deletion was obtained in other tissues...
- Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model
Lutz W D Weber
Institute of Toxicology, GSF National Research Center for Environment and Health, Munich, P O Box 1129, D 85758 Neuherberg FRG
Crit Rev Toxicol 33:105-36. 2003
..potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage...
- Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis
Kathryn Moynihan Ramsey
Department of Medicine, Northwestern University Feinberg School of Medicine, 2200 Campus Drive, Evanston, IL 60208 3500, USA
Science 324:651-4. 2009
..In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1...
- Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver
Shu Hao Hsu
Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH, USA
J Clin Invest 122:2871-83. 2012
miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication...
- Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus
, Sciences II, , CH-1211 Geneva, Switzerland
Genes Dev 14:2950-61. 2000
..Food-induced phase resetting proceeds faster in liver than in kidney, heart, or pancreas, but after 1 wk of daytime feeding, the phases of circadian gene expression are ..
- Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study
Department of Biochemistry, , Paris, France
Lancet 357:1069-75. 2001
BACKGROUND: Liver biopsy is thought mandatory for management of patients with hepatitis C virus (HCV) infection, especially for staging fibrosis...
- A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Biol Chem 285:6706-15. 2010
..These data are consistent with PNPLA3-I148M promoting triglyceride accumulation by limiting triglyceride hydrolysis...
- Organogenesis and development of the liver
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Dev Cell 18:175-89. 2010
Embryonic development of the liver has been studied intensely, yielding insights that impact diverse areas of developmental and cell biology...
- The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors
Department of Medicine, Unit of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland
Genes Dev 24:345-57. 2010
..The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks...
- Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology
De Broski R Herbert
University of Cape Town, Health Sciences Faculty, 7925 Cape Town, South Africa
Immunity 20:623-35. 2004
..Together, this shows that alternative macrophages are essential during schistosomiasis for protection against organ injury through downregulation of egg-induced inflammation...