Emerging Role of Nuclear Receptors for the Treatment of NAFLD and NASH

Therapeutic landscape for NAFLD in 2020

(2020) Brent A. Neuschwander-Tetri   GASTROENTEROLOGY

Cilofexor, a Nonsteroidal FXR Agonist, in Non‐Cirrhotic Patients with Nonalcoholic Steatohepatitis: A Phase 2 Randomized Controlled Trial

(2020) Keyur Patel et al.   HEPATOLOGY

Dual apoC-II mimetic and apoC-III antagonist for hypertriglyceridaemia

(2020) Karina Huynh   Nature Reviews Cardiology

Agonist of RORA Attenuates Non-Alcoholic Fatty Liver Progression in Mice via Upregulation of microRNA 122

(2020) Chofit Chai et al.   GASTROENTEROLOGY

PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice

(2020) Yaping Wang et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The PPAR α/γ Agonist Saroglitazar Improves Insulin Resistance and Steatohepatitis in a Diet Induced Animal Model of Nonalcoholic Fatty Liver Disease

(2020) Divya P. Kumar et al.   Scientific Reports

REV-ERB agonism improves liver pathology in a mouse model of NASH

(2020) Kristine Griffett et al.   PLoS One

Circadian rhythms and exercise — re-setting the clock in metabolic disease

(2019) Brendan M. Gabriel et al.   Nature Reviews Endocrinology

NLRP3 inflammasome activation from Kupffer cells is involved in liver fibrosis of Schistosoma japonicum-infected mice via NF-κB

(2019) Wen-Juan Zhang et al.   Parasites & Vectors

Liver-specific RORα deletion does not affect the metabolic susceptibility to western style diet feeding

(2019) Antonio Molinaro et al.   Molecular Metabolism

Circadian clock protein Rev-erbα regulates neuroinflammation

(2019) Percy Griffin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

SAT-352-A combination of the ACC inhibitor GS-0976 and the nonsteroidal FXR agonist GS-9674 improves hepatic steatosis, biochemistry, and stiffness in patients with non-alcoholic steatohepatitis

(2019) Eric Lawitz et al.   JOURNAL OF HEPATOLOGY

Past, present and future perspectives in nonalcoholic fatty liver disease

(2019) Arun J. Sanyal   Nature Reviews Gastroenterology & Hepatology

The dual PPAR-α/γ agonist saroglitazar ameliorates thioacetamide-induced liver fibrosis in rats through regulating leptin

(2019) Mirhan N. Makled et al.   NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

Farnesoid X nuclear receptor agonists for the treatment of nonalcoholic steatohepatitis

(2019) Vasiliki Venetsanaki et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Hematopoietic Npc1 mutation shifts gut microbiota composition in Ldlr−/− mice on a high-fat, high-cholesterol diet

(2019) Tom Houben et al.   Scientific Reports

Pharmacological activation of REV-ERBα represses LPS-induced microglial activation through the NF-κB pathway

(2018) Dong-kai Guo et al.   ACTA PHARMACOLOGICA SINICA

Modulation of the NLRP3 inflammasome pathway mediates the anti-inflammatory action of indoleamine dioxygenase in experimental NASH

(2018) E. Vivoli et al.   DIGESTIVE AND LIVER DISEASE

Su1522 - Proof of Concept Study of an Apoptosis-Signal Regulating Kinase (ASK-1) Inhibitor (Selonsertib) in Combination with an Acetyl-Coa Carboxylase Inhibitor (GS-0976) or a Farnesoid X Receptor (FXR) Agonist (GS-9674) in NASH

(2018) Eric Lawitz et al.   GASTROENTEROLOGY

Nuclear Receptor Subfamily 1 Group D Member 1 Regulates Circadian Activity of NLRP3 Inflammasome to Reduce the Severity of Fulminant Hepatitis in Mice

(2018) Benoit Pourcet et al.   GASTROENTEROLOGY

Update on FXR Biology: Promising Therapeutic Target?

(2018) Chang Han   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

New insights into NAFLD and subclinical coronary atherosclerosis

(2018) Lisa B. VanWagner   JOURNAL OF HEPATOLOGY

Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate

(2018) Benaïssa Boubia et al.   JOURNAL OF MEDICINAL CHEMISTRY

Mechanisms of NAFLD development and therapeutic strategies

(2018) Scott L. Friedman et al.   NATURE MEDICINE

Pre-clinical vascular damage in metabolic syndrome: Correlation between nafld and carotid disease

(2018) V. Veca et al.   ATHEROSCLEROSIS

Interleukin-17 Integrates Hepatic Steatosis and Inflammation in Nonalcoholic Fatty Liver Disease

(2018) Xiong Ma   GASTROENTEROLOGY

REVERBa couples the circadian clock to hepatic glucocorticoid action

(2018) Giorgio Caratti et al.   JOURNAL OF CLINICAL INVESTIGATION

Inability to form NLRP3 inflammasome complex leads to decreased inflammation and prevents fibrosis formation in mice after chronic bile duct ligation

(2018) M Frissen et al.   ZEITSCHRIFT FUR GASTROENTEROLOGIE

The Role of PPAR-δ in Metabolism, Inflammation, and Cancer: Many Characters of a Critical Transcription Factor

(2018) Yi Liu et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

RORγ regulates the NLRP3 inflammasome

(2018) Cyrielle Billon et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

REV-ERBα integrates colon clock with experimental colitis through regulation of NF-κB/NLRP3 axis

(2018) Shuai Wang et al.   Nature Communications

Indazole-based ligands for estrogen-related receptor α as potential anti-diabetic agents

(2017) Raymond J. Patch et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Direct activation of Nlrp3 inflammasome in hepatic stellate cells leads to upregulation of fibrotic markers

(2017) M.E. Inzaugarat et al.   JOURNAL OF HEPATOLOGY

Pharmacokinetics of selonsertib, GS-9674, and/or GS-0976 in combination in healthy subjects

(2017) C.H. Nelson et al.   JOURNAL OF HEPATOLOGY

NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice

(2017) Auvro R. Mridha et al.   JOURNAL OF HEPATOLOGY

Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH)

(2017) David C. Tully et al.   JOURNAL OF MEDICINAL CHEMISTRY

Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models

(2017) Mukul R. Jain et al.   LIVER INTERNATIONAL

Liver-specific deletion of RORα aggravates diet-induced nonalcoholic steatohepatitis by inducing mitochondrial dysfunction

(2017) Hyeon-Ji Kim et al.   Scientific Reports

RORα Induces KLF4-Mediated M2 Polarization in the Liver Macrophages that Protect against Nonalcoholic Steatohepatitis

(2017) Yong-Hyun Han et al.   Cell Reports

Metabolic Characterization of a Novel RORα Knockout Mouse Model without Ataxia

(2017) Cyrielle Billon et al.   Frontiers in Endocrinology

Elafibranor, an Agonist of the Peroxisome Proliferator−Activated Receptor−α and −δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening

(2016) Vlad Ratziu et al.   GASTROENTEROLOGY

Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD

(2016) Alexandra Montagner et al.   GUT

Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats

(2016) Geraldine Harriman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NADPH oxidase is implicated in the pathogenesis of oxidative phosphorylation dysfunction in mice fed a high-fat diet

(2016) Inmaculada García-Ruiz et al.   Scientific Reports

Inhibition of RORα/γ suppresses atherosclerosis via inhibition of both cholesterol absorption and inflammation

(2016) Cyrielle Billon et al.   Molecular Metabolism

Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

(2016) Jieyi Li et al.   PLoS One

Liver X receptors at the intersection of lipid metabolism and atherogenesis

(2015) Stephen D. Lee et al.   ATHEROSCLEROSIS

Suppression of atherosclerosis by synthetic REV-ERB agonist

(2015) Sadichha Sitaula et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis

(2015) Colin A. Flaveny et al.   CANCER CELL

PPARs and ERRs: molecular mediators of mitochondrial metabolism

(2015) Weiwei Fan et al.   CURRENT OPINION IN CELL BIOLOGY

Gut–Liver Axis in Alcoholic Liver Disease

(2015) Gyongyi Szabo   GASTROENTEROLOGY

Altered hepatic gene expression in nonalcoholic fatty liver disease is associated with lower hepatic n-3 and n-6 polyunsaturated fatty acids

(2015) Bianca M. Arendt et al.   HEPATOLOGY

Discovery of 6-(4-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic Acid: A Novel FXR Agonist for the Treatment of Dyslipidemia

(2015) Michael J. Genin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Trials of obeticholic acid for non-alcoholic steatohepatitis – Authors' reply

(2015) Brent A Neuschwander-Tetri et al.   LANCET

The LXR inverse agonist SR9238 suppresses fibrosis in a model of non-alcoholic steatohepatitis

(2015) Kristine Griffett et al.   Molecular Metabolism

The multiple universes of estrogen-related receptor α and γ in metabolic control and related diseases

(2014) Étienne Audet-walsh et al.   ACTA PHARMACOLOGICA SINICA

Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

(2014) Yang Jiao et al.   ACTA PHARMACOLOGICA SINICA

NLRP3 inflammasome activation is required for fibrosis development in NAFLD

(2014) Alexander Wree et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

Liver X receptors in lipid metabolism: opportunities for drug discovery

(2014) Cynthia Hong et al.   NATURE REVIEWS DRUG DISCOVERY

Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications - a review

(2014) Bogna Grygiel-Górniak   Nutrition Journal

Molecular and Genetic Crosstalks between mTOR and ERRα Are Key Determinants of Rapamycin-Induced Nonalcoholic Fatty Liver

(2013) Cédric Chaveroux et al.   Cell Metabolism

Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH

(2013) Salvatore Sutti et al.   HEPATOLOGY

NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice

(2013) Alexander Wree et al.   HEPATOLOGY

T0901317, a potent LXR agonist, is an inverse agonist of CAR

(2013) Yuichiro Kanno et al.   JOURNAL OF TOXICOLOGICAL SCIENCES

Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease

(2013) Melania Gaggini et al.   Nutrients

A Liver-Selective LXR Inverse Agonist That Suppresses Hepatic Steatosis

(2012) Kristine Griffett et al.   ACS Chemical Biology

Identification of a Selective RORγ Ligand That Suppresses TH17 Cells and Stimulates T Regulatory Cells

(2012) Laura A. Solt et al.   ACS Chemical Biology

N-methylthioureas as new agonists of retinoic acid receptor-related orphan receptor

(2012) Yohan Park et al.   ARCHIVES OF PHARMACAL RESEARCH

Increase of oxidative stress in NASH by increased levels of citrate

(2012) B. van de Wier⁎ et al.   FREE RADICAL BIOLOGY AND MEDICINE

Rev-erb  and Rev-erb  coordinately protect the circadian clock and normal metabolic function

(2012) A. Bugge et al.   GENES & DEVELOPMENT

Bile acids in nonalcoholic steatohepatitis: Inserting nuclear receptors into the circle

(2012) Chiara Gabbi et al.   HEPATOLOGY

Orphan Nuclear Receptor Estrogen-Related Receptor γ (ERRγ) Is Key Regulator of Hepatic Gluconeogenesis

(2012) Don-Kyu Kim et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

378 FUNCTIONAL ROLE OF REV-ERB IN MODULATION OF HEPATIC STELLATE CELL TRANSDIFFERENTIATION

(2012) T. Li et al.   JOURNAL OF HEPATOLOGY

Non-alcoholic steatohepatitis: The role of oxidized low-density lipoproteins

(2012) Sofie M.A. Walenbergh et al.   JOURNAL OF HEPATOLOGY

Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists

(2012) Laura A. Solt et al.   NATURE

Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β

(2012) Han Cho et al.   NATURE

Gene Expression Profiling Unravels Cancer-Related Hepatic Molecular Signatures in Steatohepatitis but Not in Steatosis

(2012) Julia Starmann et al.   PLoS One

NASH and atherosclerosis are two aspects of a shared disease: Central role for macrophages

(2011) Veerle Bieghs et al.   ATHEROSCLEROSIS

Exercise and PGC-1α-Independent Synchronization of Type I Muscle Metabolism and Vasculature by ERRγ

(2011) Vihang A. Narkar et al.   Cell Metabolism

Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease

(2011) Y. Tang et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle

(2011) P. Lau et al.   DIABETOLOGIA

ASH and NASH

(2011) F. Scaglioni et al.   DIGESTIVE DISEASES

Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis

(2011) Anabela P. Rolo et al.   FREE RADICAL BIOLOGY AND MEDICINE

Retinoic acid receptor-related orphan receptor α-induced activation of adenosine monophosphate-activated protein kinase results in attenuation of hepatic steatosis

(2011) Eun-Jin Kim et al.   HEPATOLOGY

Liver X receptors bridge hepatic lipid metabolism and inflammation

(2011) Yuan LIU et al.   Journal of Digestive Diseases

Identification of Diaryl Ether-Based Ligands for Estrogen-Related Receptor α as Potential Antidiabetic Agents

(2011) Raymond J. Patch et al.   JOURNAL OF MEDICINAL CHEMISTRY

Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity

(2011) Jun R. Huh et al.   NATURE

Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand

(2011) Laura A. Solt et al.   NATURE

Linking the inflammasome to obesity-related disease

(2011) Tiffany Horng et al.   NATURE MEDICINE

Transcriptional profiling reveals a role for RORα in regulating gene expression in obesity-associated inflammation and hepatic steatosis

(2011) Hong Soon Kang et al.   PHYSIOLOGICAL GENOMICS

The nuclear receptor REV-ERB  mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines

(2011) J. E. Gibbs et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

GSK4112, a Small Molecule Chemical Probe for the Cell Biology of the Nuclear Heme Receptor Rev-erbα

(2010) Daniel Grant et al.   ACS Chemical Biology

Identification of SR1078, a Synthetic Agonist for the Orphan Nuclear Receptors RORα and RORγ

(2010) Yongjun Wang et al.   ACS Chemical Biology

Identification of SR8278, a Synthetic Antagonist of the Nuclear Heme Receptor REV-ERB

(2010) Douglas Kojetin et al.   ACS Chemical Biology

Identification of SR3335 (ML-176): A Synthetic RORα Selective Inverse Agonist

(2010) Naresh Kumar et al.   ACS Chemical Biology

Functional crosstalk of CAR–LXR and ROR–LXR in drug metabolism and lipid metabolism

(2010) Lei Xiao et al.   ADVANCED DRUG DELIVERY REVIEWS

Liver X Receptor Signaling Pathways and Atherosclerosis

(2010) Anna C. Calkin et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

MS326 LXR ACTIVATION WITH TO901317 AND GW3965 IN MICE: DIFFERENTIAL EFFECTS ON LIVER AND INTESTINE, BUT NO NEGATIVE IMPACT ON BONE

(2010) J. Prawitt et al.   ATHEROSCLEROSIS SUPPLEMENTS

A second class of nuclear receptors for oxysterols: Regulation of RORα and RORγ activity by 24S-hydroxycholesterol (cerebrosterol)

(2010) Yongjun Wang et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS

Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease

(2010) Gökhan S. Hotamisligil   CELL

Acute Inhibition of Fatty Acid Import Inhibits GLUT4 Transcription in Adipose Tissue, but Not Skeletal or Cardiac Muscle Tissue, Partly Through Liver X Receptor (LXR) Signaling

(2010) B. A. Griesel et al.   DIABETES

Epidemiology of Non-Alcoholic Fatty Liver Disease

(2010) Stefano Bellentani et al.   DIGESTIVE DISEASES

The homeobox protein Prox1 is a negative modulator of ERR /PGC-1  bioenergetic functions

(2010) A. Charest-Marcotte et al.   GENES & DEVELOPMENT

Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease

(2010) Giovanni Targher et al.   HEPATOLOGY

Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites

(2010) Brent A. Neuschwander-Tetri   HEPATOLOGY

Estrogen-related Receptor γ Is a Key Regulator of Muscle Mitochondrial Activity and Oxidative Capacity

(2010) Shamina M. Rangwala et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Constitutive activation of LXR in macrophages regulates metabolic and inflammatory gene expression: identification of ARL7 as a direct target

(2010) Cynthia Hong et al.   JOURNAL OF LIPID RESEARCH

Rev-erb-α: an integrator of circadian rhythms and metabolism

(2009) Hélène Duez et al.   JOURNAL OF APPLIED PHYSIOLOGY

Modulation of Retinoic Acid Receptor-related Orphan Receptor α and γ Activity by 7-Oxygenated Sterol Ligands

(2009) Yongjun Wang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Safety, Pharmacokinetics, and Pharmacodynamics of Single Doses of LXR-623, a Novel Liver X-Receptor Agonist, in Healthy Participants

(2009) Arie Katz et al.   JOURNAL OF CLINICAL PHARMACOLOGY

REV-ERBα Participates in Circadian SREBP Signaling and Bile Acid Homeostasis

(2009) Gwendal Le Martelot et al.   PLOS BIOLOGY

Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis

(2008) Paola Loria et al.   CLINICAL SCIENCE

Transcriptional Control of Energy Homeostasis by the Estrogen-Related Receptors

(2008) Vincent Giguère   ENDOCRINE REVIEWS

Regulation of Bile Acid Synthesis by the Nuclear Receptor Rev-erbα

(2008) Hélène Duez et al.   GASTROENTEROLOGY

Nuclear Hormone Receptors for Heme: REV-ERBα and REV-ERBβ Are Ligand-Regulated Components of the Mammalian Clock

(2008) Thomas P. Burris   MOLECULAR ENDOCRINOLOGY

Minireview: Liver X Receptor β: Emerging Roles in Physiology and Diseases

(2008) Chiara Gabbi et al.   MOLECULAR ENDOCRINOLOGY

GW3965, a synthetic liver X receptor (LXR) agonist, reduces angiotensin II-mediated pressor responses in Sprague-Dawley rats

(2007) C E Leik et al.   BRITISH JOURNAL OF PHARMACOLOGY