Article
Cell Biology
Greg Guthrie, Caitlin Vonderohe, Douglas Burrin
Summary: This review summarizes the current literature on the protein FGF19, its target receptors, and the biological pathways they target through unique signaling cascades.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jing Zeng, Jiangao Fan, Huiping Zhou
Summary: Chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), gradually progress to liver fibrosis, cirrhosis, and failure. Disruption of bile acid metabolism and intrahepatic circulation plays a crucial role in accelerating the progression of cholestatic liver diseases. Bile acids not only act as detergents for nutrition absorption but also function as key signaling molecules that regulate hepatic metabolism and immune responses. This review focuses on the role of bile acid-mediated signaling in cholestatic liver disease.
CELL AND BIOSCIENCE
(2023)
Article
Multidisciplinary Sciences
Yoichi Takimoto, Po-sung Chu, Nobuhiro Nakamoto, Yuya Hagihara, Yohei Mikami, Kentar Miyamoto, Rei Morikawa, Toshiaki Teratani, Nobuhito Taniki, Sota Fujimori, Takahiro Suzuki, Yuzo Koda, Rino Ishihara, Masataka Ichikawa, Akira Honda, Takanori Kanai
Summary: The resolution process of liver fibrosis after liver injury withdrawal is still not fully understood. In this study, the pro-fibrogenic role of Toll-like receptor 4 (TLR4) signaling in tissue fibroblasts was explored. Interestingly, pharmacological inhibition of TLR4 signaling in vivo in two murine models resulted in a significant delay in fibrosis resolution. Single-cell transcriptome analysis revealed a cluster of Tlr4-expressing myeloid cells that played a restorative role in the resolution process. Further investigation suggested a microbiome-dependent nature of the delayed resolution after gut sterilization. These findings provide insights into the pro-fibrolytic role of myeloid TLR4 signaling and potential targets for anti-fibrotic therapy.
Review
Biochemistry & Molecular Biology
Takeshi Katafuchi, Makoto Makishima
Summary: Bile acids have detergent and hormone-like properties. FXR and FGF15/19 are considered as potential therapeutic targets for metabolic syndrome and cholestatic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Baixue Li, Shi-Ying Cai, James L. Boyer
Summary: Retinoic acid receptors (RARs) and retinoid X receptors (RXRs), activated by retinoids, play crucial roles in various biological processes such as embryo development, homeostasis, cell proliferation, differentiation and death. In liver physiology, RAR/RXR heterodimers regulate lipid and bile acid synthesis and metabolism, cholesterol transport in macrophages, and fibrogenesis in hepatic stellate cells. Specific genes carrying out these functions are regulated by RAR/RXR in liver cells, providing a mechanistic understanding of their roles in liver physiology. Still, detailed signaling mechanisms of RAR/RXR in regulating liver gene expression remain to be fully elucidated in future studies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Endocrinology & Metabolism
Helene Johansson, Jonas Norskov Sondergaard, Carl Jorns, Claudia Kutter, Ewa C. S. Ellis
Summary: Bile acids (BAs) are essential for lipid absorption in the intestine, and their metabolism is tightly regulated by feedback mechanisms. FGF19 plays a crucial role in maintaining BA homeostasis, while CDCA can independently regulate BA synthesis by increasing FGF19 expression and subsequently reducing BA synthesis.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Nutrition & Dietetics
Agostino Di Ciaula, Leonilde Bonfrate, Jacek Baj, Mohamad Khalil, Gabriella Garruti, Frans Stellaard, Helen H. Wang, David Q. -H. Wang, Piero Portincasa
Summary: Bile acids are synthesized in the liver and play important roles in the digestion and absorption of dietary fat, cholesterol, and lipid-soluble vitamins. They also act as signaling molecules and are tightly regulated by various factors. Maintaining bile acid homeostasis is crucial for metabolic processes and liver health.
Article
Biochemistry & Molecular Biology
Alex Zaufel, Sandra M. W. van de Wiel, Lu Yin, Gunter Fauler, Daphne Chien, Xinzhong Dong, John F. Gilmer, Jennifer K. Truong, Paul A. Dawson, Stan F. J. van de Graaf, Peter Fickert, Tarek Moustafa
Summary: Secondary (iso) BAs cooperatively activate FXR in the presence of endogenous BAs, which is important to consider in diseases linked to disturbances in BA enterohepatic cycling; the study shows that UDCA is only effective in the presence of endogenous FXR ligands.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Angela E. Dean, Francois Reichardt, Sayeepriyadarshini Anakk
Summary: Sex differences exist in nutrient metabolism and hormone regulation in the gastrointestinal tract, possibly influenced by nuclear receptors. Some nuclear receptors show different activity and target gene expression between males and females, potentially affecting overall metabolic decisions.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Alexandra A. Tsitrina, Noreen Halimani, Irina N. Andreichenko, Marat Sabirov, Mikhail Nesterchuk, Nataliya O. Dashenkova, Roman Romanov, Elena V. Bulgakova, Arsen Mikaelyan, Yuri Kotelevtsev
Summary: 4-methylumbelliferone (4MU) is a well-known inhibitor of hyaluronic acid synthesis and approved for cholestasis treatment. In animal models, 4MU has various effects including reducing inflammation, fibrosis, body weight, serum cholesterol, insulin resistance, as well as inhibiting tumor progression and metastasis. Through database analysis and transcriptome analysis, potential targets of 4MU were identified as enzymes and transcription factors, including members of the nuclear receptor superfamily. These findings suggest that 4MU has multiple targets and can regulate cell metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Hao Chen, Lan-Lan Li, Yan Du
Summary: Liver diseases, characterized by metabolic disorder, have become a global public health problem with high morbidity and mortality. Kruppel-like factor 15 (KLF15), a zinc-finger transcription factor mainly enriched in liver, is rapidly activated during fasting and regulates various metabolic processes in the liver. This review summarizes the latest advances of KLF15 in metabolic reprogramming and its role in acute liver injury, hepatitis B virus, and autoimmune hepatitis, aiming to assess the potential of KLF15 as a therapeutic target and prognostic biomarker for liver diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Immunology
Yushu Yang, XiaoSong He, Manuel Rojas, Patrick S. C. Leung, Lixia Gao
Summary: Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, leading to cirrhosis and liver failure. Current treatments have limitations, and there is a need for further research to investigate underlying mechanisms and develop more effective therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xinran Cai, Gregory M. Young, Wen Xie
Summary: PXR and CAR, two nuclear receptors highly expressed in the liver, have major potentials to affect liver pathophysiology by regulating the homeostasis of endobiotics.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Pharmacology & Pharmacy
Kevin M. Tveter, Esther Mezhibovsky, Yue Wu, Diana E. Roopchand
Summary: Beyond their role as emulsifiers of lipophilic compounds, bile acids (BAs) are signaling endocrine molecules that show differential affinity and specificity for a variety of canonical and non-canonical BA receptors. Dysregulation of BA metabolism or signaling has emerged as a feature of chronic disease. Dietary polyphenols are associated with decreased risk of metabolic syndrome, type-2 diabetes, hepatobiliary and cardiovascular disease by altering the gut microbial community, the BA pool, and BA signaling. This review provides an overview of BA metabolism and summarizes studies linking the cardiometabolic improvements of dietary polyphenols to their modulation of BA metabolism and signaling pathways, and the gut microbiota.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Jing Zhong, Xiaofang He, Xinxin Gao, Qiaohong Liu, Yu Zhao, Ying Hong, Weize Zhu, Juan Yan, Yifan Li, Yan Li, Ningning Zheng, Yiyang Bao, Hao Wang, Junli Ma, Wenjin Huang, Zekun Liu, Yuanzhi Lyu, Xisong Ke, Wei Jia, Cen Xie, Yiyang Hu, Lili Sheng, Houkai Li
Summary: Nonalcoholic fatty liver disease (NAFLD) is associated with disrupted bile acid homeostasis. The authors demonstrate that hyodeoxycholic acid (HDCA) ameliorates NAFLD by inhibiting the formation of RAN/CRM1/PPARα nuclear export heterotrimer, which leads to increased nuclear localization of PPARα and activation of fatty acid oxidation.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Marcin Krawczyk, Heike Bantel, Monika Rau, Joern M. Schattenberg, Frank Gruenhage, Anita Pathil, Muenevver Demir, Johannes Kluwe, Tobias Boettler, Susanne N. Weber, Andreas Geier, Frank Lammert
JOURNAL OF HUMAN GENETICS
(2018)
Article
Multidisciplinary Sciences
Ali Canbay, Julia Kaelsch, Ursula Neumann, Monika Rau, Simon Hohenester, Hideo A. Baba, Christian Rust, Andreas Geier, Dominik Heider, Jan-Peter Sowa
Article
Gastroenterology & Hepatology
Stephanie Liebig, Neele Stoeckmann, Andreas Geier, Monika Rau, Joern M. Schattenberg, Matthias J. Bahr, Michael P. Manns, Elmar Jaeckel, Klaus Schulze-Osthoff, Heike Bantel
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
(2019)
Article
Gastroenterology & Hepatology
Mohamed Alsenbesy, Monika Rau, Johannes Weiss, Oliver Goetze, Andreas Geier
ZEITSCHRIFT FUR GASTROENTEROLOGIE
(2019)
Review
Pharmacology & Pharmacy
Monika Rau, Andreas Geier
Summary: NAFLD is a recognized disease entity with increasing prevalence. Regulatory agencies have identified an unmet medical need for NASH treatment and initiated expedited drug development. Current research focuses on drugs with metabolic, anti-inflammatory, and anti-fibrotic effects for treating NASH, with a potential future for combination therapy.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Jonathan Trujillo-Viera, Rabih El-Merahbi, Vanessa Schmidt, Till Karwen, Angel Loza-Valdes, Akim Strohmeyer, Saskia Reuter, Minhee Noh, Magdalena Wit, Izabela Hawro, Sabine Mocek, Christina Fey, Alexander E. Mayer, Mona C. Loeffler, Ilka Wilhelmi, Marco Metzger, Eri Ishikawa, Sho Yamasaki, Monika Rau, Andreas Geier, Mohammed Hankir, Florian Seyfried, Martin Klingenspor, Grzegorz Sumara
Summary: The study reveals the significant role of protein kinase D2 in lipid absorption, where its activity promotes TG transfer within enterocytes, affecting the development of obesity and diabetes. This finding suggests that targeting PKD2 may hold promise as a therapeutic approach for obesity.
EMBO MOLECULAR MEDICINE
(2021)
Review
Gastroenterology & Hepatology
Christoph G. Dietrich, Monika Rau, Andreas Geier
Summary: NAFLD is a common liver disease, especially prevalent in patients with metabolic syndrome and in Western countries. Complications include fibrosis, cirrhosis, hepatocellular carcinoma, as well as increased risk for cardiovascular disease, extrahepatic neoplasia, and other organ damage.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Multidisciplinary Sciences
Monika Rau, Peter Buggisch, Stefan Mauss, Klaus H. W. Boeker, Hartwig Klinker, Tobias Mueller, Albrecht Stoehr, Jorn M. Schattenberg, Andreas Geier
Summary: Liver steatosis in chronic HCV infection does not appear to contribute significantly to fibrosis progression in this unique cohort.
Article
Medicine, General & Internal
Katharina John, Martin Franck, Sherin Al Aoua, Monika Rau, Yvonne Huber, Joern M. Schattenberg, Andreas Geier, Matthias J. Bahr, Heiner Wedemeyer, Klaus Schulze-Osthoff, Heike Bantel
Summary: The combination of FIB-4 and M30 allows for a more reliable identification of patients at risk for progressed NAFLD and has the potential to improve patient stratification.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Florian P. Reiter, Monika Rau, Volker Kunzmann, Ralph Kickuth, Ingo Klein, Olaf Neumann, Albrecht Stenzinger, Peter Schirmacher, Andreas Geier
Summary: Immunotherapy has shown promising efficacy in late-line treatment of advanced HCC, even in fourth-line scenarios. Established biomarkers predicting response to immunotherapy were not detected in this case, but mutations in SETD2 and LRP1B genes may explain the exceptional response.
ZEITSCHRIFT FUR GASTROENTEROLOGIE
(2023)
Article
Gastroenterology & Hepatology
Andreas Geier, Monika Rau, Anita Pathil-Warth, Manfred von der Ohe, Joern Schattenberg, Nektarios Dikopoulos, Kerstin Stein, Yvonne Serfert, Thomas Berg, Peter Buggisch, Muenevver Demir, Elke Roeb, Bianka Wiebner, Heiner Wedemeyer, Stefan Zeuzem, Wolf P. Hofmann
Summary: The German NAFLD-Registry is a prospective study that aims to describe clinical characteristics and observe outcomes in patients with NAFLD. From the baseline data of the first 501 patients, it was found that approximately 13% had a high risk for advanced fibrosis, about one-third had a liver stiffness value greater than 9.6kPa, and 10% had a clinical diagnosis of liver cirrhosis. Comorbidities such as arterial hypertension, hypercholesterolemia, and type 2 diabetes mellitus were more prevalent in high-risk patients.
ZEITSCHRIFT FUR GASTROENTEROLOGIE
(2023)
Article
Nutrition & Dietetics
Bianca Heller, Florian P. Reiter, Hans Benno Leicht, Cornelia Fiessler, Ina Bergheim, Peter U. Heuschmann, Andreas Geier, Monika Rau
Summary: The study reveals a strong link between daily salt intake and salt-intake-related behavior, with sex-specific differences in an MASLD cohort. Specific behavioral approaches, such as improving salt awareness, may enhance adherence to lifestyle changes in male patients in high cardiovascular risk populations.
Meeting Abstract
Gastroenterology & Hepatology
Monika Rau, Sarah Kaps, Hans Benno Leicht, Florian P. Reiter, Marcin Krawczyk, Andreas Geier
JOURNAL OF HEPATOLOGY
(2022)
Meeting Abstract
Gastroenterology & Hepatology
Monika Rau, Theresa Schmitt, Marcin Krawczyk, Luetjohann Dieter, Maria Monte, Jose Marin, Andreas Geier
JOURNAL OF HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Monika Rau, Ateequr Rehman, Marcus Dittrich, Albert K. Groen, Heike M. Hermanns, Florian Seyfried, Niklas Beyersdorf, Thomas Dandekar, Philip Rosenstiel, Andreas Geier
UNITED EUROPEAN GASTROENTEROLOGY JOURNAL
(2018)