Article
Plant Sciences
Lina Kong, Renchao Dong, Kai Huang, Xiaohui Wang, Dalong Wang, Nan Yue, Changyuan Wang, Pengyuan Sun, Jiangning Gu, Haifeng Luo, Kexin Liu, Jingjing Wu, Huijun Sun, Qiang Meng
Summary: The study aimed to investigate whether the FXR agonist Yangonin (YAN) exerted hepatoprotective effects against ALD, and elucidate the mechanisms in vitro and in vivo. Results showed that YAN activated FXR to improve lipid homeostasis, alleviate liver histopathological progression, reduce ethanol-induced cholestasis, improve bile acid homeostasis, and attenuate hepatocyte damage and inflammation. These protective effects were demonstrated to be mediated by FXR-regulated target gene modulation.
Article
Biochemistry & Molecular Biology
Yansong Zhang, Siyuan Lin, Jingyu Peng, Xiaojuan Liang, Qi Yang, Xue Bai, Yajuan Li, Jinhua Li, Wei Dong, Yue Wang, Ying Huang, Yumeng Pei, Jiabao Guo, Wanni Zhao, Zhe Zhang, Min Liu, Alan Jian Zhu
Summary: The study reveals that dietary essential amino acids can improve NAFLD by inducing polyubiquitination of Plin2, a lipid droplet-stabilizing protein. Leucine and isoleucine can activate the Ubr1 enzyme to target Plin2 for degradation. Additionally, activation of Ubr1 family proteins can significantly improve obesity-induced and high-fat diet-induced hepatic steatosis in mice.
Article
Cell & Tissue Engineering
Li Chen, Tingying Jiao, Weiwei Liu, Yuhong Luo, Jue Wang, Xiaozhen Guo, Xiao Tong, Zemin Lin, Chuying Sun, Kanglong Wang, Yifan He, Yuwei Zhang, Hualing Xu, Jiawen Wang, Jianping Zuo, Qiurong Ding, Shijun He, Frank J. Gonzalez, Cen Xie
Summary: This study reveals that disrupted bile acid (BA) homeostasis, specifically increased cholic acid (CA) levels and induced cytochrome P450 8B1 (CYP8B1) synthesis, plays a significant role in the pathogenesis of colitis. CA inhibits peroxisome proliferator-activated receptor alpha (PPAR alpha), resulting in impaired fatty acid oxidation (FAO) and intestinal stem cell (ISC) renewal, leading to more severe colitis. Activation of the farnesoid X receptor (FXR) suppresses CYP8B1 expression and ameliorates colitis. These findings suggest that targeting the hepatic CYP8B1-CA axis may be a beneficial strategy for treating inflammatory bowel disease (IBD).
Article
Biochemistry & Molecular Biology
Marine Hanse, Samina Akbar, Hamed Layeghkhavidaki, Frances T. Yen
Summary: Garcinia cambogia extract (GCE) can lower plasma triglyceride levels and promote weight loss, but may lead to compensatory mechanisms of increased liver and muscle lipids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yanan Yang, Chongming Wu
Summary: The gut microbiome plays a crucial role in human health by participating in nutrient acquisition, energy regulation, and maintenance of overall health. Manipulating the gut microbiota through dietary supplements has proven to be effective in improving human health. Bile acids are extensively metabolized by the gut microbes and control various metabolic processes, such as energy homeostasis and glucose and lipid metabolism, through activation of the farnesoid X receptor (FXR). This review focuses on the effects of dietary supplements on FXR signaling and how they promote human health by affecting the gut microbiota and bile acids-FXR signaling axis.
Article
Biochemistry & Molecular Biology
Adrian Bouzas Munoz, Juan Antonio Gimenez-Bastida, Aurora Garcia Tejedor, Claudia Monika Haros, Marta Gomez de Cedron, Ana Ramirez de Molina, Jose Moises Laparra Llopis
Summary: The study showed that administration of SETIs improved survival and decreased tumor burden by modulating monocyte-derived macrophages, playing a key role in diet-induced HCC development. This suggests a potential therapeutic strategy to improve the hepatic innate immune response and create a better antitumoral environment in early stages of HCC development.
Article
Pharmacology & Pharmacy
Huiling Hu, Nannan Sun, Haiyan Du, Yuqing He, Kunyi Pan, Xiuli Liu, Xiaoxia Lu, Jie Wei, Mianmian Liao, Chaohui Duan
Summary: Previous studies have shown that PLZF plays a role in promoting gluconeogenic gene expression, hepatic glucose output, and consequent hyperglycemia. However, its role in regulating lipid metabolism was unknown. This study revealed that PLZF is an essential regulator of hepatic lipid and glucose metabolism. Overexpression of PLZF in the liver led to fatty liver, inflammation, impaired glucose tolerance, and insulin sensitivity. Knockdown of PLZF in obese mice alleviated hepatic steatosis. The underlying mechanism involved PLZF activating SREBP-1c gene transcription by binding to its promoter fragment, which depended on its interaction with SIRT1 to induce a repressor-to-activator conversion. These findings suggest that modulating PLZF expression in the liver could be a potential therapeutic approach for treating NAFLD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Environmental Sciences
Changqing Li, Nan Shen, Shaohua Yang, Hui-Li Wang
Summary: This study investigated the effects of Bisphenol A (BPA) on hepatic lipid metabolism and its potential mechanisms in mice. The results showed that BPA exposure led to NAFLD features and upregulation of APOD could repair the damage caused by BPA. Therefore, it is important to carefully examine BPA exposure in chronic liver metabolic disorders or diseases.
Article
Nutrition & Dietetics
Long-jiao Wang, Guo-ping Zhao, Xi-fan Wang, Xiao-xue Liu, Yi-xuan Li, Li-li Qiu, Xiao-yu Wang, Fa-zheng Ren
Summary: Glycochenodeoxycholate (GCDCA), a steroid, can induce the expression of hepcidin and reduce serum iron levels. GCDCA regulates hepcidin by activating the FXR and BMP6/ALK3-SMAD signaling pathway.
Article
Biochemistry & Molecular Biology
Yuan Cui, Yan Yin, Shilan Li, Zhengli Wu, Yisha Xie, Qingfan Qian, Hao Yang, Xinli Li
Summary: This study found that apple polyphenol extract (APE) can prevent and regulate bile acid metabolism and gut microbiota by modulating circadian rhythms, protecting the host from circadian disruption.
Article
Integrative & Complementary Medicine
Zhe Wang, Xu-Ling Li, Kin-Fong Hong, Ting-Ting Zhao, Rui-Xue Dong, Wei-Ming Wang, Yun-Tong Li, Gui-Lin Zhang, Jing Lin, Ding-Kun Gui, You-Hua Xu
Summary: Astragalus Radix, a common traditional Chinese medicine, may modulate the progression of diabetes through influencing bile acid and lipid metabolism, possibly by upregulating GLUT2 and CYP7A1 expression and involving FXR and TGR5.
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Seiya Takemoto, Masataka Nakano, Tatsuki Fukami, Miki Nakajima
Summary: The study reveals that m(6)A modification negatively regulates CES2 expression by impacting its protein level, hydrolase activity, and lipid accumulation, thereby affecting pharmacokinetics and lipid metabolism. The regulation of CES2 by m(6)A modification highlights the potential significance of epitranscriptomic modifications in drug response and metabolic processes.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Lili Ding, Eryun Zhang, Qiaoling Yang, Lihua Jin, Kyle M. Sousa, Bingning Dong, Yangmeng Wang, Jui Tu, Xiaoxiao Ma, Jingyan Tian, Hongli Zhang, Zhipeng Fang, Ana Guan, Yixin Zhang, Zhengtao Wang, David D. Moore, Li Yang, Wendong Huang
Summary: The study suggests that vertical sleeve gastrectomy (VSG) achieves its metabolic benefits by reducing intestinal bile acids and fat absorption levels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Plant Sciences
Guochao Song, Bin Zou, Jing Zhao, Fengyi Weng, Yue Li, Xiaoqing Xu, Shuang Zhang, Dongming Yan, Jingyi Jin, Xin Sun, Chenghai Liu, Furong Qiu
Summary: This study investigated the molecular mechanism of how Yinchen decoction (YCD) protects against intrahepatic cholestasis induced by a 1% cholic acid diet. The findings showed that YCD restores bile acid homeostasis by activating the liver FXR/SHP and ileal FXR/FGF15 signaling pathways, thereby protecting against cholestatic liver injury. Furthermore, chlorogenic acid and caffeic acid in YCD may be the pharmacological agents responsible for its protective effects against cholestatic liver injury.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Biology
Gilberto Garcia, Hanlin Zhang, Sophia Moreno, C. Kimberly Tsui, Brant Michael Webster, Ryo Higuchi-Sanabria, Andrew Dillin, Randy Y. Hampton
Summary: Changes in lipid metabolism are associated with aging and age-related diseases, including proteopathies. This study identified let-767 as an essential gene for both lipid and ER protein homeostasis in Caenorhabditis elegans. Knockdown of let-767 affects lipid stores, ER morphology, and the induction of the UPRER. A reduction in lipogenic pathways restores UPRER induction in animals with reduced let-767 by blocking the metabolite 3-oxoacyl.
Article
Endocrinology & Metabolism
P. Comeglio, S. Filippi, E. Sarchielli, A. Morelli, I. Cellai, C. Corno, A. Pini, L. Adorini, G. B. Vannelli, M. Maggi, L. Vignozzi
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2019)
Article
Multidisciplinary Sciences
S. Di Matteo, L. Nevi, D. Costantini, D. Overi, G. Carpino, S. Safarikia, F. Giulitti, C. Napoletano, E. Manzi, A. M. De Rose, F. Melandro, M. Bragazzi, P. B. Berloco, F. Giuliante, G. Grazi, A. Giorgi, V. Cardinale, L. Adorini, E. Gaudio, D. Alvaro
Article
Gastroenterology & Hepatology
Juliette Mouries, Paola Brescia, Alessandra Silvestri, Ilaria Spadoni, Marcel Sorribas, Reiner Wiest, Erika Mileti, Marianna Galbiati, Pietro Invernizzi, Luciano Adorini, Giuseppe Penna, Maria Rescigno
JOURNAL OF HEPATOLOGY
(2019)
Article
Multidisciplinary Sciences
Beatrice Anfuso, Claudio Tiribelli, Luciano Adorini, Natalia Rosso
SCIENTIFIC REPORTS
(2020)
Article
Gastroenterology & Hepatology
Vanessa Pataia, Saraid McIlvride, Georgia Papacleovoulou, Caroline Ovadia, Julie A. K. McDonald, Annika Wahlstrom, Eugene Jansen, Luciano Adorini, David Shapiro, Julian R. Marchesi, Hanns-Ulrich Marschall, Catherine Williamson
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2020)
Article
Multidisciplinary Sciences
Andrea Ferrigno, Giuseppina Palladini, Laura Giuseppina Di Pasqua, Clarissa Berardo, Plinio Richelmi, Massimiliano Cadamuro, Luca Fabris, Stefano Perlini, Luciano Adorini, Mariapia Vairetti
Article
Chemistry, Medicinal
Giuseppina Palladini, Marta Cagna, Laura Giuseppina Di Pasqua, Luciano Adorini, Anna Cleta Croce, Stefano Perlini, Andrea Ferrigno, Clarissa Berardo, Mariapia Vairetti
Summary: This study investigated the ability of the FXR agonist OCA to modulate MMPs in distant organs such as the kidney, and found that OCA can protect the kidney by reducing TNF-alpha-mediated expression of MMPs after liver ischemia/reperfusion.
Article
Gastroenterology & Hepatology
Caroline Morel, Vivek Chowdhary, Prashanth Thevkar Nagesh, Marcelle Ribeiro, Danielle Hawryluk, Donna Catalano, Luciano Adorini, Gyongyi Szabo
Summary: The pathogenesis of alcohol-induced liver disease (ALD) in FXR KO mice is associated with altered ethanol metabolism and increased oxidative stress, providing new insights into the protective function of FXR in ALD.
LIVER INTERNATIONAL
(2023)
Article
Nutrition & Dietetics
Justine Gillard, Corinne Picalausa, Christoph Ullmer, Luciano Adorini, Bart Staels, Anne Tailleux, Isabelle A. Leclercq
Summary: Activation of TGR5 has beneficial effects on glucose tolerance and MAFLD, particularly when activated in the enterohepatic system.
Article
Medicine, Research & Experimental
M. Marzano, Bruno Fosso, C. Colliva, E. Notario, D. Passeri, M. Intranuovo, A. Gioiello, L. Adorini, G. Pesole, R. Pellicciari, A. Moschetta, R. M. Gadaleta
Summary: This study investigated the effects of TC-100 on intestinal mucosa integrity and cecal microbiome composition in a rodent model of bile flow obstruction. The results showed that TC-100 activates FXR and regulates bile acid homeostasis and gut microbiota composition, preventing early signs of intestinal mucosal damage.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoxin X. Wang, Cen Xie, Andrew E. Libby, Suman Ranjit, Jonathan Levi, Komuraiah Myakala, Kanchan Bhasin, Bryce A. Jones, David J. Orlicky, Shogo Takahashi, Alexander Dvornikov, David E. Kleiner, Stephen M. Hewitt, Luciano Adorini, Jeffrey B. Kopp, Kristopher W. Krausz, Avi Rosenberg, James L. McManaman, Charles E. Robertson, Diana Ir, Daniel N. Frank, Yuhuan Luo, Frank J. Gonzalez, Enrico Gratton, Moshe Levi
Summary: The dual FXR-TGR5 agonist INT-767 can prevent the progression of Western diet-induced NASH in mice by modulating bile acid composition, improving liver fatty acid synthesis and uptake, reducing inflammation, and maintaining mitochondrial function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Rotonya M. Carr, Yun Li, Lillian Chau, Elliot S. Friedman, Jung-Jin Lee, Luciano Adorini, Mary Erickson, Luna Zaru, Reshma Shringarpure, Leigh Macconell, Kyle Bittinger, Hongzhe Li, Gary D. Wu
Summary: This study compared the microbiome features between 279 patients with NASH and 3 healthy control cohorts, revealing differences in microbial diversity and specific species associated with NASH. Additionally, lower levels of specific fecal bile acids were found in NASH patients and correlated with plasma C4 levels, suggesting a potential role as diagnostic biomarkers.
News Item
Biotechnology & Applied Microbiology
Elie Dolgin
NATURE BIOTECHNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Luciano Adorini, Michael Trauner
Summary: The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor that plays a crucial role in regulating various metabolic processes in the liver and intestine. FXR activation has emerged as a potential pharmacological target for the treatment of non-alcoholic steatohepatitis (NASH), a severe metabolic disorder with no approved pharmacological treatments. This review summarizes the preclinical and clinical features of the most advanced FXR agonists and evaluates their potential in NASH treatment.
JOURNAL OF HEPATOLOGY
(2023)
Article
Endocrinology & Metabolism
P. Comeglio, S. Filippi, E. Sarchielli, A. Morelli, I. Cellai, C. Corno, L. Adorini, G. B. Vannelli, M. Maggi, L. Vignozzi
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2019)