Article
Nutrition & Dietetics
Ji Ho Suh, Kang Ho Kim, Margaret E. Conner, David D. Moore, Geoffrey A. Preidis
Summary: This study identifies a new mechanism, regulated by SIRT1, that may contribute to the liver's failed metabolic responses in individuals with chronic undernutrition.
FRONTIERS IN NUTRITION
(2022)
Article
Cell Biology
Monika Adamowicz, Agnieszka Kempinska-Podhorodecka, Joanna Abramczyk, Jesus M. Banales, Piotr Milkiewicz, Malgorzata Milkiewicz
Summary: The expression of PPARα is reduced in the liver of patients with primary biliary cholangitis (PBC), likely due to overexpression of miR-155. Ursodeoxycholic acid (UDCA) effectively reduces the expression of miR-155, preventing the suppression of PPARα.
Article
Genetics & Heredity
Jia Luo, Zheng Yan, Manyun Dai, Liping Xu, Haoyue Zhang, Yang Xi, Julin Yang, Aiming Liu
Summary: This study aimed to investigate the role of PPAR alpha in modifying the circadian clock and its relevance to NAFLD. The authors used a mouse model and hepatocyte experiments to verify the effects of PPAR alpha on CLOCK regulation and lipid accumulation. They found that high-fat diet led to the down-regulation of CLOCK in the liver, and this down-regulation was dependent on PPAR alpha activity. Furthermore, they observed that down-regulation of hepatic CLOCK by basal PPAR alpha contributed to the inhibition of NAFLD development, while inhibition of CLOCK by activated PPAR alpha was involved in the inhibition of NAFLD by PPAR alpha agonists.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Biochemistry & Molecular Biology
Xingming Li, Yuliang Cheng, Jiayi Li, Chang Liu, He Qian, Genyi Zhang
Summary: Torularhodin, a beta-carotene-like compound from Sporidiobolus pararoseus, has a protective effect against hepatic dyslipidemia and inflammation induced by high-fat diet. It can prevent health problems caused by high-fat diet.
Article
Integrative & Complementary Medicine
Cui Shuang, Pan Xiao-Jie, Ge Chao-Liang, Guo Yi-Tong, Zhang Peng-Fei, Yan Ting-Ting, Zhou Ji-Yu, He Qing-Xian, Cheng Long-Hao, Wang Guang-Ji, Hao Hai-Ping, Wang Hong
Summary: Silymarin protects against NAFLD by activating PPARα to reduce lipid accumulation in mice, and it is not recommended to take silymarin and classical PPARα agonists simultaneously for NAFLD therapy.
CHINESE JOURNAL OF NATURAL MEDICINES
(2021)
Article
Endocrinology & Metabolism
Chenxiao Zhang, Tengfei Ma, Chang Liu, Ding Ma, Jian Wang, Meng Liu, Jinjun Ran, Xueting Wang, Xiaobei Deng
Summary: PM2.5 exposure can lead to extensive metabolic disturbances, particularly in lipid and amino acid metabolism. It is associated with the enrichment of disease pathways and signaling pathways related to non-alcoholic fatty liver disease, type II diabetes mellitus, TGF-beta, AMPK, and mTOR. Accumulation of acylcarnitine in liver tissue restricts lipid consumption and contributes to hepatic steatosis. The aberrant expression of key transcription factors, such as PPARs and SREBP1, may play a regulatory role in lipid metabolic disorders.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christopher S. Krumm, Xu Xu, Curtis J. Bare, Corey D. Holman, Sander Kersten, Lukas E. Dow, Ann-Hwee Lee, David E. Cohen
Summary: Activation of the CREBH-Fgf21 axis can reverse diet-induced obesity, insulin resistance, and hepatic steatosis, while also enhancing insulin sensitivity and glucose tolerance.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yixiu Zhao, Na Sun, Xia Song, Jia Zhu, Tianshuo Wang, Zhiqi Wang, Yuanyuan Yu, Jing Ren, Huan Chen, Tingting Zhan, Jiaying Tian, Chunyue Ma, Jian Huang, Jinhui Wang, Yan Zhang, Baofeng Yang
Summary: This study has identified a novel anthraquinone compound called ESME that activates AdipoR2 to inhibit hepatic lipogenesis and promote fatty acid oxidation, thereby alleviating experimental hepatic steatosis. ESME has a strong binding potential with AdipoR2 and shows potent efficacy and safety in reducing hepatic steatosis and protecting hepatocytes. Oral administration of ESME reduces liver lipid production and accumulation in hamsters and Apoe-/-mice induced by high-fat diet.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Zhe Zhang, Pan Diao, Xuguang Zhang, Takero Nakajima, Takefumi Kimura, Naoki Tanaka
Summary: Pemafibrate (PEM) is a novel lipid-lowering drug that can efficiently reduce serum triglyceride (TG) levels and increase fibroblast growth factor 21 (FGF21) without causing hepatotoxicity in mice when used at a clinically relevant dose. It binds to peroxisome proliferator-activated receptor alpha (PPAR alpha) and activates it specifically in the liver, leading to enhanced fatty acid uptake and beta-oxidation.
Article
Biochemistry & Molecular Biology
Federica Mannino, Giovanni Pallio, Domenica Altavilla, Francesco Squadrito, Giovanna Vermiglio, Alessandra Bitto, Natasha Irrera
Summary: Lycopene administration reduces triglycerides and cholesterol blood levels, decreases the extent of atherosclerotic plaques, and increases Nrf-2 positivity staining in the endothelium, supporting its use to reduce atherosclerosis.
Article
Gastroenterology & Hepatology
Jingjing Duan, Zhuo Wang, Ran Duan, Chenxinhui Yang, Ruolin Zhao, Qi Feng, Yuanyuan Qin, Jingwei Jiang, Shouyong Gu, Kaiyan Lv, Libo Zhang, Bixia He, Lutz Birnbaumer, Song Yang, Zhen Chen, Yong Yang
Summary: This study found elevated levels of ACSL4 in the livers of NAFLD patients, inhibition of which can reduce lipid accumulation. Abemaciclib, a selective ACSL4 inhibitor, shows promise as a potential therapeutic approach for NAFLD.
Article
Gastroenterology & Hepatology
Dinghui Liu, Juan Pang, Weijuan Shao, Jianqiu Gu, Yong Zeng, Housheng Hansen He, Wenhua Ling, Xiaoxian Qian, Tianru Jin
Summary: This study suggests that liraglutide-stimulated hepatic Fgf21 expression may require GLP-1R to be expressed in extrahepatic organs and reveals that hepatic FGF21 is necessary for liraglutide to lower body weight and improve hepatic lipid homeostasis. These findings advance our understanding of the mechanisms behind the function of GLP-1-based drugs in NAFLD.
Article
Food Science & Technology
Zhi Tao, Lihu Zhang, Tao Wu, Xianying Fang, Linguo Zhao
Summary: The study findings suggest that ECH may protect against ethanol-induced liver injuries by alleviating oxidative stress and hepatic steatosis through affecting the SREBP-1c/FASN pathway via PPAR-alpha. This indicates the potential of ECH in safeguarding the liver from damage caused by ethanol.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Biology
Yo Han Lee, Hyun-Jun Jang, Sounkou Kim, Sun Sil Choi, Keon Woo Khim, Hye-jin Eom, Jimin Hyun, Kyeong Jin Shin, Young Chan Chae, Hongtae Kim, Jiyoung Park, Neung Hwa Park, Chang-Yun Woo, Chung Hwan Hong, Eun Hee Koh, Dougu Nam, Jang Hyun Choi
Summary: The study identifies that MIR20B targets PPARA and plays a significant role in NAFLD, with overexpression of MIR20B leading to increased hepatic lipid accumulation and triglyceride levels, and inhibiting FA oxidation and mitochondrial biogenesis. Inhibition of MIR20B can enhance FA oxidation and uptake, improving insulin sensitivity and reducing NAFLD progression.
Article
Biochemistry & Molecular Biology
Xiaoyan Chen, Wenjie Shi, Yong Xie, Yunwu Wang, Qian Yao, Huajing Ke, Xuan Xu, Hui Liu, Pi Liu, Xiaojiang Zhou
Summary: This study investigates the role of Kruppel-like factor 14 (KLF14) in hepatic lipid metabolism in nonalcoholic steatohepatitis (NASH). The expression of KLF14 was found to be decreased in NASH patients and mice fed a high-fat diet. Knockdown of KLF14 promoted the progression of hepatic steatosis by downregulating fatty acid oxidation genes.
Article
Gastroenterology & Hepatology
Naoyuki Fujimori, Takefumi Kimura, Naoki Tanaka, Tomoo Yamazaki, Taiki Okumura, Hiroyuki Kobayashi, Shun-Ichi Wakabayashi, Yuki Yamashita, Ayumi Sugiura, Jonathan Pham, Sai P. Pydi, Kenji Sano, Satoru Joshita, Takeji Umemura
Summary: Accurate detection of hepatic fibrosis stage is crucial for predicting the outcome of patients with NAFLD. The 2-Step PLT16-AST44 method, based on standard clinical markers, demonstrated high sensitivity, specificity, and predictive values in detecting early-stage hepatic fibrosis, making it a simple yet effective detection system for NAFLD patients.
HEPATOLOGY RESEARCH
(2022)
Article
Medicine, General & Internal
Makoto Harada, Takero Nakajima, Yosuke Yamada, Daiki Aomura, Akinori Yamaguchi, Kosuke Sonoda, Naoki Tanaka, Koji Hashimoto, Yuji Kamijo
Summary: This study aimed to investigate the significance of serum sulfatide levels in patients with AAV. The results showed that serum sulfatide levels are closely correlated with inflammatory response and crescentic glomerulonephritis.
JOURNAL OF CLINICAL MEDICINE
(2022)
Editorial Material
Gastroenterology & Hepatology
Naoki Tanaka, Akira Honda
HEPATOLOGY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Takefumi Kimura, Sai P. Pydi, Lei Wang, Dhanush Haspula, Yinghong Cui, Huiyan Lu, Gabriele M. Koenig, Evi Kostenis, Gregory R. Steinberg, Oksana Gavrilova, Juergen Wess
Summary: This study found that by activating adipocyte G(q) signaling, the increased lipolysis in obese individuals can be prevented, leading to improved glucose and lipid homeostasis. This has important implications for the development of novel anti-diabetic drugs based on GPCR.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Pan Diao, Yaping Wang, Fangping Jia, Xiaojing Wang, Xiao Hu, Takefumi Kimura, Yoshiko Sato, Kyoji Moriya, Kazuhiko Koike, Jun Nakayama, Naoki Tanaka
Summary: This study revealed that diets rich in SFA and TFA, but not Chol, might stimulate hepatic angiogenesis/lymphangiogenesis mainly through the JNK-HIF1α-VEGF-C axis. Our observations indicate an importance of dietary fat species for preventing hepatic tumorigenesis.
Article
Biochemistry & Molecular Biology
Momoko Hayashi, Yoshibumi Kuwabara, Kuniji Ito, Yoshiaki Hojo, Fumiaki Arai, Kazuki Kamijima, Masakazu Takeiri, Xiaojing Wang, Pan Diao, Jun Nakayama, Naoki Tanaka
Summary: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that can progress to liver fibrosis and cancer. Patients with NASH often have a high prevalence of atherosclerosis and related cardiovascular diseases, necessitating simultaneous management of both conditions. Rodents are commonly used as animal models for NASH, but their lipoprotein profiles differ significantly from humans, making it difficult to replicate the pathology of NASH patients with atherosclerosis. Rabbits, on the other hand, have lipoprotein metabolism more similar to humans and could be a promising candidate for assessing NASH and atherosclerosis. A rabbit NASH model was developed by treating Japanese White rabbits with a newly developed high-fat high-cholesterol diet for 16 weeks, resulting in NASH and advanced fibrosis development. Atherosclerotic lesions were also observed in the aorta. This rabbit NASH model could contribute to the exploration of concurrent treatment options for human NASH and atherosclerosis.
Article
Biochemistry & Molecular Biology
Takanobu Iwadare, Takefumi Kimura, Hideo Kunimoto, Naoki Tanaka, Shun-ichi Wakabayashi, Tomoo Yamazaki, Taiki Okumura, Hiroyuki Kobayashi, Yuki Yamashita, Ayumi Sugiura, Satoru Joshita, Takeji Umemura
Summary: This study aimed to identify predictors of Pemafibrate (PEM) efficacy for hypertriglyceridemia accompanying non-alcoholic fatty liver disease (HTG-NAFLD) in clinical practice. The results showed that female HTG-NAFLD patients with higher transaminase and fat mass % levels may be preferentially indicated for PEM treatment.
Review
Nutrition & Dietetics
Michiharu Komatsu, Naoki Tanaka, Takefumi Kimura, Masahide Yazaki
Summary: Mutations in the SLC25A13 gene are responsible for diseases associated with citrin deficiency (CD), including neonatal intrahepatic cholestasis caused by citrin deficiency and adult-onset type II citrullinemia (CTLN2). CD patients from childhood to adulthood have seemingly good health due to metabolic compensation and specific dietary habits. However, carbohydrate overload and alcohol consumption may trigger the sudden onset of CTLN2, leading to hyperammonemia and consciousness disturbance. This review summarizes the clinical and nutritional features of CD-associated fatty liver disease and highlights promising nutritional interventions.
Article
Gastroenterology & Hepatology
Taiki Okumura, Takefumi Kimura, Yu Hihara, Katsuaki Inoue, Atsushi Maruyama, Satoru Joshita, Takeji Umemura
Summary: This article describes a rare case of immune thrombocytopenic purpura (ITP) coexisting with primary biliary cholangitis (PBC) and localized cutaneous systemic sclerosis (LcSSc). A careful review of similar cases suggests that other collagen disease complications, positive antinuclear antibody, and positive antiphospholipid antibody in PBC can support a diagnosis of ITP. Clinicians should be vigilant for the occurrence of ITP when rapid thrombocytopenia is observed during the course of PBC.
CLINICAL JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Gastroenterology & Hepatology
Takanobu Iwadare, Takefumi Kimura, Yusuke Nagata, Hiroshi Suzuki, Hideo Kunimoto, Hiroyuki Kitabatake, Ayako Seki, Yasuhide Ochi, Etsuo Hara, Takeji Umemura
Summary: Malignant peritoneal mesothelioma (MPeM) is a rare and poor prognosis disease that affects the mesothelial cells of the peritoneum. A 48-year-old man without asbestos exposure presented with abdominal pain. Imaging revealed a Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface and peritoneal thickening, which led to the diagnosis of MPeM. Treatment with cisplatin and pemetrexed resulted in improvement.
CLINICAL JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Engineering, Biomedical
Yuanyuan Ding, Yuta Koda, Babita Shashni, Naoki Takeda, Xuguang Zhang, Naoki Tanaka, Yuji Nishikawa, Yukio Nagasaki
ACTA BIOMATERIALIA
(2023)
Article
Oncology
Qianqian Zheng, Masaya Kawaguchi, Hayato Mikami, Pan Diao, Xuguang Zhang, Zhe Zhang, Takero Nakajima, Takanobu Iwadare, Takefumi Kimura, Jun Nakayama, Naoki Tanaka
Summary: Non-alcoholic steatohepatitis (NASH) can lead to liver cirrhosis and hepatocellular carcinoma (HCC). This study developed a new mouse model of NASH-liver cirrhosis-HCC sequence with shorter occurrence time and similar pathological characteristics to humans. The model is expected to be used for the development of novel compounds for the treatment of NASH patients.
Article
Gastroenterology & Hepatology
Takefumi Kimura, Takanobu Iwadare, Shun-ichi Wakabayashi, Seema Kuldeep, Tomoyuki Nakajima, Tomoo Yamazaki, Daiki Aomura, Hamim Zafar, Mai Iwaya, Satoru Joshita, Takeshi Uehara, Sai P. Pydi, Naoki Tanaka, Takeji Umemura
Summary: This study identified THBS2/TSP2 as highly expressed in HSCs and involved in regulating fibrogenesis in NAFLD patients. THBS2/TSP2 may potentially serve as a target for anti-fibrotic therapy in NAFLD.
LIVER INTERNATIONAL
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Takeji Umemura, Yuki Yamashita, Satoru Joshita, Takefumi Kimura, Junko Hirohara, Toshiaki Nakano, Atsumasa Komori, Atsushi Tanaka
