Editorial Material
Gastroenterology & Hepatology
Manal F. Abdelmalek
Summary: In 2020, there were significant advances in nonalcoholic fatty liver disease, including new insights into pathophysiology, advancements in non-invasive diagnostics, and the publication of interim results from the first phase III trial showing improvement in hepatic fibrosis.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Review
Immunology
Ke-qian Chen, Bo-yi Ke, Lu Cheng, Xiao-qing Yu, Zong-bao Wang, Shu-zhi Wang
Summary: With the development of the social economy, unhealthy living habits and eating styles are gradually affecting people's health in recent years. NAFLD, as a chronic liver disease, has become an increasingly serious public health problem due to these factors. Inflammasomes, as a protein complex, play a crucial role in the development of NAFLD and other diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Sami Qadri, Noora Ahlholm, Ida Lonsmann, Paola Pellegrini, Anni Poikola, Panu K. Luukkonen, Kimmo Porthan, Anne Juuti, Henna Sammalkorpi, Anne K. Penttila, Roberta D'Ambrosio, Giorgio Soardo, Diana J. Leeming, Morten Karsdal, Johanna Arola, Stergios Kechagias, Serena Pelusi, Mattias Ekstedt, Luca Valenti, Hannes Hagstrom, Hannele Yki-Jarvinen
Summary: This study investigated the impact of obesity on the performance of liver fibrosis biomarkers in NAFLD and found that ADAPT and FIB-4 are the best-performing biomarkers in obese patients, unaffected by body mass index.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Meixi Wang, Jianrui Li, Hu Li, Biao Dong, Jing Jiang, Nannan Liu, Jiali Tan, Xuekai Wang, Lei Lei, Hongying Li, Han Sun, Mei Tang, Huiqiang Wang, Haiyan Yan, Yuhuan Li, Jiandong Jiang, Zonggen Peng
Summary: This study identified 17-beta-hydroxysteroid dehydrogenase type 13 (HSD17B13) as a potential target for the treatment of non-alcoholic fatty liver disease (NAFLD). The researchers found that HSD17B13 was highly expressed in the livers of NAFLD patients and its overexpression facilitated the progression of NAFLD. In mouse models, overexpressing HSD17B13 worsened liver steatosis and fibrosis, while down-regulating its expression showed therapeutic effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Reeju Amatya, Donghee Lee, Kyoung Ah Min, Meong Cheol Shin
Summary: Nonalcoholic fatty liver disease (NAFLD) has become a global epidemic and is the primary cause of chronic liver disease. Without medical intervention, NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The progression of NAFLD is influenced by genetics, metabolic disorders, and immunologic factors. Fortunately, extensive research has led to the discovery of potent drug candidates, and efforts have been made to improve their druggability. This review provides an overview of clinical trial drug candidates and discusses strategies for developing better drugs.
Article
Pharmacology & Pharmacy
Hongguo Guan, Yiyan Wang, Huitao Li, Qiqi Zhu, Xiaoheng Li, Guang Liang, Ren-Shan Ge
Summary: WZS08 is a potent inhibitor of rat, mouse, and human 11 beta-hydroxysteroid dehydrogenase 1, effectively treating non-alcoholic fatty liver disease in mice by reducing liver fat content and improving liver morphology.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Endocrinology & Metabolism
Sarah Beland-Bonenfant, Alexia Rouland, Jean-Michel Petita, Bruno Verges
Summary: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease worldwide. Lipidomic studies have been used to understand the pathophysiology of NAFLD and identify potential biomarkers. Lipidomic abnormalities associated with NAFLD include changes in free fatty acid distribution, increased ceramides, reduced phosphatidylcholine/phosphatidylethanolamine ratio, and increased eicosanoids. These lipid abnormalities may contribute to NASH and liver fibrosis by inducing mitochondrial dysfunction, apoptosis, inflammation, oxidation, and endoplasmic reticulum stress. Further research is needed to determine their predictive value for liver steatosis, NASH, or liver fibrosis.
DIABETES & METABOLISM
(2023)
Review
Biochemistry & Molecular Biology
Georgiana-Emmanuela Gilca-Blanariu, Daniela Simona Budur, Dana Elena Mitrica, Elena Gologan, Oana Timofte, Gheorghe Gh Balan, Vasile Andrei Olteanu, Gabriela Stefanescu
Summary: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, and early diagnosis and staging are crucial for preventing complications. Noninvasive diagnostic and staging methods, such as imaging techniques and serum biomarkers, have been developed to replace liver biopsy. Due to the complexity of NAFLD's pathophysiology, biomarkers can assay different processes involved. This article reviews the currently validated noninvasive methods and promising biomarkers, including biomarker panels and the combination of validated evaluation methods and serum markers.
Review
Medicine, Research & Experimental
Evangelia Makri, Antonis Goulas, Stergios A. Polyzos
Summary: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with its prevalence rising due to increasing rates of obesity and type 2 diabetes. The pathogenesis of NAFLD is not fully understood, with factors such as adipokines, gut microbiota, and genetic predisposition playing a role in addition to weight gain and insulin resistance. Liver biopsy is currently the gold standard for diagnosis and staging, but early use of noninvasive biomarkers is essential for identifying patients at different stages of the disease.
ARCHIVES OF MEDICAL RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Wen-Yue Liu, Mohammed Eslam, Kenneth Zheng, Hong-Lei Ma, Rafael S. Rios, Min-Zhi Lv, Gang Li, Liang-Jie Tang, Pei-Wu Zhu, Xiao-Dong Wang, Christopher D. Byrne, Giovanni Targher, Jacob George, Ming-Hua Zheng
Summary: This study aimed to investigate the associations of HSD17B13 gene variants with metabolic-associated fatty liver disease in Chinese patients. The results showed that rs72613567 and rs6531975 variants of HSD17813 were associated with increased risk and protective effect on fibrosis, respectively.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2021)
Review
Multidisciplinary Sciences
George Agyapong, Farzaneh Dashti, Bubu A. A. Banini
Summary: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and a leading indication for liver transplantation in the United States. This manuscript provides an overview of NAFLD risk factors, natural history, diagnosis, and current management strategies.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Julia A. Golubeva, Anna F. Sheptulina, Anastasia Yu. Elkina, Ekaterina O. Liusina, Anton R. Kiselev, Oxana M. Drapkina
Summary: Non-alcoholic fatty liver disease (NAFLD) and arterial hypertension (AH) are common non-communicable diseases worldwide. They often coexist and are associated with each other regardless of the presence of other metabolic factors.
Review
Pharmacology & Pharmacy
Evangelia S. Makri, Antonis Goulas, Stergios A. Polyzos
Summary: NAFLD is a common liver disease with potentially severe consequences, and pharmacological therapy is still lacking. SGLT-2 inhibitors show promising potential for treating NAFLD, especially in improving liver function.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Endocrinology & Metabolism
Maria Irene Bellini, Irene Urciuoli, Giovanni Del Gaudio, Giorgia Polti, Giovanni Iannetti, Elena Gangitano, Eleonora Lori, Carla Lubrano, Vito Cantisani, Salvatore Sorrenti, Vito D'Andrea
Summary: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide and is closely associated with insulin resistance and diabetes. Treatment for NAFLD depends on the severity of the disease, including abstinence from alcohol, dietary changes, and reduction of risk factors, as well as procedures like weight loss surgery to improve liver condition.
WORLD JOURNAL OF DIABETES
(2022)
Review
Endocrinology & Metabolism
Seonghwan Hwang, Hwayoung Yun, Sungwon Moon, Ye Eun Cho, Bin Gao
Summary: NAFLD encompasses a range of liver disorders, with NASH characterized by increased liver injury and inflammation, where neutrophils play a critical role. The review outlines the functions of neutrophils in promoting the progression of fatty liver to NASH and their potential as therapeutic targets.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Neurosciences
Renan Fudoli Lins Vieira, Vitor Rosetto Munoz, Rafael Lima Junqueira, Fellipe de Oliveira, Rafael Calais Gaspar, Susana Castelo Branco Ramos Nakandakari, Suleyma de Oliveira Costa, Marcio Alberto Torsoni, Adelino S. R. da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Eduardo Rochete Ropelle, Iman Zaghloul, Rania A. Mekary, Jose Rodrigo Pauli
Summary: Time-restricted feeding (TRF) alone can reduce weight gain and increase fatty acid oxidation, while TRF combined with aerobic exercise (TRF+Exe) shows additional benefits such as increased oxygen consumption and ketone body production. TRF+Exe also attenuates the negative effects of high-fat diet on insulin signaling pathway and leads to improved liver metabolism and glucose homeostasis.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Multidisciplinary Sciences
Traci E. LaMoia, Gina M. Butrico, Hasini A. Kalpage, Leigh Goedeke, Brandon T. Hubbard, Daniel F. Vatner, Rafael C. Gaspar, Xian-Man Zhang, Gary W. Cline, Keita Nakahara, Seungwan Woo, Atsuhiro Shimada, Maik Huttemann, Gerald Shulman
Summary: Metformin reduces hepatic gluconeogenesis by inhibiting complex IV to decrease the function of GPD2, leading to a decrease in glycerol-derived hepatic gluconeogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Letter
Gastroenterology & Hepatology
Fredrik Aberg, Panu K. Luukkonen, Martti Farkkila
JOURNAL OF HEPATOLOGY
(2022)
Article
Endocrinology & Metabolism
V. R. Munoz, R. C. Gaspar, M. C. S. Mancini, R. D. de Lima, R. F. L. Vieira, B. M. Crisol, G. C. Antunes, J. C. S. Trombeta, I. L. P. Bonfante, F. M. Simabuco, A. S. R. da Silva, C. R. Cavaglieri, E. R. Ropelle, D. E. Cintra, J. R. Pauli
Summary: The study found that short-term aerobic exercise can improve overall glucose and insulin sensitivity as well as hepatic metabolism in aged rodents. These effects contribute to late-life metabolic health and help prevent the development of age-related T2D.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Rafael S. Bricola, Andre Cordeiro, Barbara M. Crisol, Renata R. Braga, Diego G. de Melo, Matheus B. Rocha, Rafael C. Gaspar, Susana C. B. R. Nakandakari, Vagner R. R. Silva, Chadi P. Anaruma, Carlos K. Katashima, Raphael D. S. Canciglieri, Vitor R. Munoz, Isadora C. B. Pavan, Ana P. Pinto, Fernando M. Simabuco, Adelino S. R. da Silva, Leandro P. Moura, Jose R. Pauli, Dennys E. Cintra, Eduardo R. Ropelle
Summary: The dysfunction of adipose tissue metabolism is a significant feature of aging, and ABHD5 is believed to play a critical role in controlling lipolysis. This study revealed that ABHD5 content is reduced in adipose tissue of both mice and humans as they age. Additionally, high-intensity interval training was found to increase ABHD5 protein levels and restore lipolytic activity in aged mice.
CELL BIOCHEMISTRY AND FUNCTION
(2022)
Article
Endocrinology & Metabolism
Rafael C. Gaspar, Kun Lyu, Brandon T. Hubbard, Brooks P. Leitner, Panu K. Luukkonen, Sandro M. Hirabara, Ikki Sakuma, Ali Nasiri, Dongyan Zhang, Mario Kahn, Gary W. Cline, Jose Rodrigo Pauli, Rachel J. Perry, Kitt F. Petersen, Gerald I. Shulman
Summary: This study found that regular aerobic exercise can prevent the increase of muscle fat content, as well as reduce the content of sn-1,2-diacylglycerols (DAGs) in the cell membrane and the activation of protein kinase C (PKC), thus maintaining muscle insulin sensitivity.
Article
Biochemistry & Molecular Biology
Susana Castelo Branco Ramos Nakandakari, Rafael Calais Gaspar, Gabriel Keine Kuga, Camila de Oliveira Ramos, Renan Fudoli Vieira, Thaiane da Silva Rios, Vitor Rosetto Munoz, Marcella Ramos Sant'ana, Fernando Moreira Simabuco, Adelino Sanchez Ramos da Silva, Leandro Pereira Moura, Eduardo Rochete Ropelle, Jose Rodrigo Pauli, Dennys Esper Cintra
Summary: Long-term high-fat diet affects adipose tissue and leads to metabolic disorders. Short-term high-fat diet affects neuronal signaling pathways. Flaxseed oil containing omega-3 fatty acids protects against increased food intake and fasting glucose, but not inflammation.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Vitor Rosetto Munoz, Jose Diego Botezelli, Rafael Calais Gaspar, Alisson L. da Rocha, Renan Fudoli Lins Vieira, Barbara Moreira Crisol, Renata Rosseto Braga, Matheus Brandemarte Severino, Susana Castelo Branco Ramos Nakandakari, Gabriel Calheiros Antunes, Sergio Q. Brunetto, Celso D. Ramos, Licio Augusto Velloso, Fernando Moreira Simabuco, Leandro Pereira de Moura, Adelino Sanchez Ramos da Silva, Eduardo Rochete Ropelle, Dennys Esper Cintra, Jose Rodrigo Pauli
Summary: Short-term physical exercise improves glucose metabolism and homeostasis in a mouse model with hyperinsulinemia and hyperglycemia. Endurance training affects transcriptomic and mitochondrial activity, while strength training mainly influences post-translational mechanisms and protein synthesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Panu K. Luukkonen, Martti Farkkila, Antti Jula, Veikko Salomaa, Satu Mannisto, Annamari Lundqvist, Markus Perola, Fredrik Aberg
Summary: This study investigates the association between genetic variants, abdominal obesity, alcohol use and incident liver disease (ILD). Variants in genes such as PNPLA3, IFNL4, and TM6SF2 are found to be associated with ILD. Genetic risk scores (GRSs) calculated from these variants are exponentially associated with ILD, while not associated with waist-hip ratio (WHR) or alcohol use. The risk of ILD in individuals with high GRS and high WHR or alcohol use is increased by up to 90-fold.
LIVER INTERNATIONAL
(2023)
Article
Endocrinology & Metabolism
Xinyi Zhang, Won D. Lee, Brooks P. Leitner, Wanling Zhu, Andin Fosam, Zongyu Li, Rafael C. Gaspar, Alexandra A. Halberstam, Briana Robles, Joshua D. Rabinowitz, Rachel J. Perry
Summary: Cancer-related fatigue is a common complication in cancer patients, but there is currently no effective pharmaceutical treatment. However, a study has found that dichloroacetate may be a novel treatment option to maintain physical function and motivation in patients with cancer-related fatigue.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Endocrinology & Metabolism
Robson Damasceno de Lima, Renan Fudoli Lins Vieira, Vitor Rosetto Munoz, Amandine Chaix, Ana Paula Azevedo Macedo, Gabriel Calheiros Antunes, Maira Felonato, Renata Rosseto Braga, Susana Castelo Branco Ramos Nakandakari, Rafael Calais Gaspar, Adelino Sanchez Ramos da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Rania A. Mekary, Eduardo Rochete Ropelle, Jose Rodrigo Pauli
Summary: Combined time-restricted feeding (TRF) and resistance exercise training (RT) have significant effects on obesity, metabolic disorders, and nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Cell Biology
Panu K. Luukkonen, Kimmo Porthan, Noora Ahlholm, Fredrik Rosqvist, Sylvie Dufour, Xian-Man Zhang, Tiina E. Lehtimaki, Wenla Seppanen, Marju Orho-Melander, Leanne Hodson, Kitt Falk Petersen, Gerald I. Shulman, Hannele Yki-Jarvinen
Summary: The PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but its underlying pathophysiology is still unclear. This study used state-of-the-art stable isotope techniques to investigate the effect of this variant on hepatic metabolism. The findings show that homozygous carriers of the PNPLA3 I148M variant have altered hepatic mitochondrial function, leading to reduced de novo lipogenesis and increased ketogenesis.
Article
Cell Biology
Meghan Mooring, Grace A. Yeung, Panu Luukkonen, Silvia Liu, Muhammad Waqas Akbar, Gary J. Zhang, Oluwashanu Balogun, Xuemei Yu, Rigen Mo, Kari Nejak-Bowen, Masha V. Poyurovsky, Carmen J. Booth, Liza Konnikova, Gerald I. Shulman, Dean Yimlamai
Summary: Obesity leads to various metabolic diseases and CYR61 has been found to be associated with the progression of NASH. In this study, liver-specific knockout of CYR61 in mice showed improved glucose tolerance, decreased liver inflammation, and reduced fibrosis. CYR61 promoted a proinflammatory/profibrotic phenotype in infiltrating monocytes through an IRAK4/SYK/NF-kappa B signaling pathway. In vitro experiments showed that CYR61 activated a profibrotic program in macrophages in an IRAK4/SYK/NF-kappa B-dependent manner. Targeted-antibody blockade reduced CYR61-driven signaling and fibrotic development. This study highlights the key role of CYR61 in liver inflammation and fibrosis in NASH.
SCIENCE TRANSLATIONAL MEDICINE
(2023)