Article
Agriculture, Multidisciplinary
Xiangyun Tan, Yi Sun, Liang Chen, Junjie Hu, Yan Meng, Ming Yuan, Qi Wang, Shan Li, Guohua Zheng, Zhenpeng Qiu
Summary: This study aimed to evaluate the therapeutic efficacy of caffeine in a NASH mouse model. The results showed that caffeine improved hepatic steatosis and inflammatory injury by inhibiting two signaling pathways and reducing the production of proinflammatory mediators. These findings suggest that caffeine may be beneficial in the prevention and therapy of NASH.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Jiaji Hu, Hanglu Ying, Jie Yao, Longhe Yang, Wenhui Jin, Huabin Ma, Long Li, Yufen Zhao
Summary: PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated lipid accumulation and hepatic fibrosis in MCD-induced NASH mice.
FRONTIERS IN PHARMACOLOGY
(2021)
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
Plant Sciences
Daram Yang, Hyuneui Jeong, Seung-Mi Hwang, Jong-Won Kim, Hee-Won Moon, Ye-Eun Lee, Hyo-Bin Oh, Chung-berm Park, Bumseok Kim
Summary: This study assessed the effects of a mixture of Jinan Red Ginseng and licorice extracts on the progression of nonalcoholic steatohepatitis (NASH). The results showed that the mixture reduced NASH-related pathologies and regulated the expression of genes associated with inflammation, fibrosis, and lipid metabolism. Additionally, the mixture effectively reduced lipogenesis through modulating the AMPK signaling pathway.
JOURNAL OF GINSENG RESEARCH
(2022)
Article
Agriculture, Multidisciplinary
Yinhua Ni, Yating Hu, Xiaoyi Lou, Nianke Rong, Fang Liu, Congrong Yang, Aqian Zheng, Song Yang, Jianfeng Bao, Zhengwei Fu
Summary: Spermidine may improve NASH partly through regulating the THRSP signaling pathway and gut microbiota-mediated bile acid metabolism.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Yuanyuan Lei, Li Tang, Qiao Chen, Lingyi Wu, Wei He, Dianji Tu, Sumin Wang, Yuyang Chen, Shuang Liu, Zhuo Xie, Hong Wei, Shiming Yang, Bo Tang
Summary: Disulfiram (DSF) reduces Clostridium-mediated 7 alpha-dehydroxylation activity to suppress secondary bile acid biosynthesis and ameliorate NASH in mice. A self-controlled clinical trial also validates DSF regulation of the gut-liver axis in healthy men.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Sheng-liang Xin, Yan-yan Yu
Summary: The study found that ubiquitin-specific peptidase (USP)10 alleviates hepatic steatosis in nonalcoholic steatohepatitis (NASH) through promoting autophagic activity, improving inflammation and fibrosis.
DIGESTIVE AND LIVER DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Yi-Long Huang, Zhao-Qing Shen, Chen-Hua Huang, Yuan-Chi Teng, Chao-Hsiung Lin, Ting-Fen Tsai
Summary: This study demonstrates that Cisd2 dosage modulates the severity of NAFLD induced by Western diet, with haploinsufficiency exacerbating the progression to NASH and increased copy number attenuating liver pathogenesis. Transcriptomic analysis reveals significant changes in biological processes related to inflammation, lipid metabolism, and DNA replication/repair, suggesting potential therapeutic targets for WD-induced fatty liver diseases.
Article
Medicine, General & Internal
Arun J. Sanyal, Mark L. Van Natta, Jeanne Clark, Brent A. Neuschwander-Tetri, AnnaMae Diehl, Srinivasan Dasarathy, Rohit Loomba, Naga Chalasani, Kris Kowdley, Bilal Hameed, Laura A. Wilson, Katherine P. Yates, Patricia Belt, Mariana Lazo, David E. Kleiner, Cynthia Behling, James Tonascia
Summary: In this study involving patients with nonalcoholic fatty liver disease, advanced fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death over a median of 4 years of follow-up. Advanced fibrosis was also related to an increased incidence of liver decompensation events.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Multidisciplinary Sciences
Jinmei Yao, Ying Zhao
Summary: Our study found that Lp-PLA2 expression increases in a high-fat diet-induced NASH mouse model. Silencing Lp-PLA2 can reduce liver damage and inflammation, and promote autophagy. These findings suggest that by inhibiting the JAK2/STAT3 signaling pathway, silencing Lp-PLA2 can restrain NASH progression.
Article
Plant Sciences
Meixia Zhu, Zhixin Jia, Xiaoning Yan, Lirong Liu, Cong Fang, Menghan Feng, Yihang Dai, Yinhuan Zhang, Hao Wu, Beibei Huang, Yueting Li, Jie Liu, Hongbin Xiao
Summary: This study evaluated the ameliorative effects of DHG on liver inflammation and fibrosis in a methionine/ choline-deficient (MCD) diet-induced NASH rat model, and its underlying mechanism.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Nutrition & Dietetics
Dou-Dou Li, Jia-Min Ma, Ming-Jing Li, Lu-Lu Gao, Yan-Na Fan, Yan-Nan Zhang, Xiu-Juan Tao, Jian-Jun Yang
Summary: This study investigated the effects of LBP, AE, and their combination on NASH. The results showed that LBP or AE reduced the severity of NASH, while the combination of LBP and AE more effectively improved liver damage and lowered levels of serum lipid and inflammation. Additionally, the combination also regulated genes involved in hepatic fatty acid synthesis and oxidation through the AMPK/PPARα/PGC-1α pathway, enhancing fatty acid oxidation.
Article
Agriculture, Multidisciplinary
Nanxuan Luo, Changqing Yang, Yurong Zhu, Qianfeng Chen, Baoshun Zhang
Summary: Diosmetin has been shown to alleviate liver lipid accumulation and inflammatory injury in NASH by regulating the STAT1/CXCL10 signal pathway. The study suggests that Diosmetin can alleviate NASH by suppressing lipogenesis and inflammation.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Khalifa Mohammad Helal, Harsono Cahyadi, J. Nicholas Taylor, Akira Okajima, Koji Tabata, Yasuaki Kumamoto, Kentaro Mochizuki, Yoshito Itoh, Tetsuro Takamatsu, Hideo Tanaka, Katsumasa Fujita, Tamiki Komatsuzaki, Yoshinori Harada
Summary: An essential challenge in diagnosing NAFLD is predicting the progression from NAFL to NASH. Hyperspectral Raman imaging can provide diagnostic information on NAFLD in rats, detecting spectral changes before histological characteristics emerge. This technique offers biomolecular distinctions among tissue states that cannot be observed through standard histopathological means, making it a useful tool for histopathologists.
Article
Multidisciplinary Sciences
Nao Hasuzawa, Keita Tatsushima, Lixiang Wang, Masaharu Kabashima, Rie Tokubuchi, Ayako Nagayama, Kenji Ashida, Yoshihiro Ogawa, Yoshinori Moriyama, Masatoshi Nomura
Summary: The VNUT inhibitor clodronate showed beneficial effects in reducing hepatic inflammation and fibrosis, preventing steatohepatitis, and protecting against acute liver injury in mouse models. In vitro experiments demonstrated that clodronate inhibited vesicular ATP release and reduced triglyceride accumulation. These findings suggest that pharmacological inhibition of VNUT may be a potential therapeutic strategy for liver inflammatory disorders.
SCIENTIFIC REPORTS
(2021)
Article
Nutrition & Dietetics
Tomoko Fujiwara, Masanori Ono, Michihiro Mieda, Hiroaki Yoshikawa, Rieko Nakata, Takiko Daikoku, Naomi Sekizuka-Kagami, Yoshiko Maida, Hitoshi Ando, Hiroshi Fujiwara
Article
Endocrinology & Metabolism
Nazmul Hasan, Naoto Nagata, Jun-ichi Morishige, Md Tarikul Islam, Zheng Jing, Ken-ichi Harada, Michihiro Mieda, Masanori Ono, Hiroshi Fujiwara, Takiko Daikoku, Tomoko Fujiwara, Yoshiko Maida, Tsuguhito Ota, Shigeki Shimba, Shuichi Kaneko, Akio Fujimura, Hitoshi Ando
Summary: This study demonstrates the impact of impaired BAT clock on energy metabolism and obesity development. Disruption of BAT clock helps maintain normal core body temperatures but may lead to reduced energy expenditure and obesity development.
MOLECULAR METABOLISM
(2021)
Article
Endocrinology & Metabolism
Mayumi Nagashimada, Kazuki Sawamoto, Yinhua Ni, Hironori Kitade, Naoto Nagata, Liang Xu, Masuko Kobori, Naofumi Mukaida, Tatsuya Yamashita, Shuichi Kaneko, Tsuguhito Ota
Summary: The CX3CL1-CX3CR1 system is crucial in regulating inflammation, particularly in obese mice with adipose tissue inflammation and insulin resistance. Deficiency in CX3CR1 signaling leads to an increase in M1 polarized macrophages, worsening glucose tolerance and insulin resistance in obese mice. Targeting the CX3CL1-CX3CR1 system may be beneficial in treating type 2 diabetes by modulating M1/M2 macrophages.
Article
Endocrinology & Metabolism
Liang Xu, Yongping Chen, Mayumi Nagashimada, Yinhua Ni, Fen Zhuge, Guanliang Chen, Haoran Li, Tongtong Pan, Tatsuya Yamashita, Naofumi Mukaida, Shuichi Kaneko, Tsuguhito Ota, Naoto Nagata
Summary: The study revealed that CCL3 plays a crucial role in the development of fatty liver disease by facilitating macrophage infiltration and M1 polarization, highlighting the potential therapeutic target of CCL3 in the treatment of NAFLD.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Nutrition & Dietetics
Hironao Okubo, Hitoshi Ando, Eisuke Nakadera, Kenichi Ikejima, Shuichiro Shiina, Akihito Nagahara
Summary: The study demonstrated that levocarnitine supplementation can effectively suppress the progression of sarcopenia in patients with hepatocellular carcinoma receiving lenvatinib therapy, and is significantly correlated with free carnitine levels.
Article
Endocrinology & Metabolism
Yinhua Ni, Fen Zhuge, Liyang Ni, Naoto Nagata, Tatsuya Yamashita, Naofumi Mukaida, Shuichi Kaneko, Tsuguhito Ota, Mayumi Nagashimada
Summary: This study investigates the roles of CX3CL1/CX3CR1 in macrophage migration and polarization in the livers of NASH mice. It is found that CX3CL1 and CX3CR1 expression is upregulated in NASH mice livers, and CX3CR1 is predominantly expressed by F4/80+ macrophages. CX3CR1 deficiency leads to increased inflammatory monocyte/macrophage infiltration and a shift towards M1 dominant macrophages, exacerbating NASH progression. Deletion of CCL2 in CX3CR1-deficient mice alleviates NASH progression by reducing macrophage infiltration and inducing a shift towards M2 dominant macrophages.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Article
Toxicology
Zheng Jing, Hironao Okubo, Jun-ichi Morishige, Pingping Xu, Nazmul Hasan, Naoto Nagata, Hitoshi Ando
Summary: This study reveals the detrimental effects of lenvatinib on OCTN2 expression, carnitine content, and mitochondrial function in skeletal muscle which may be associated with muscle toxicity.
TOXICOLOGY LETTERS
(2022)
Article
Multidisciplinary Sciences
Takayoshi Shirasaki, Satoshi Yamagoe, Tetsuro Shimakami, Kazuhisa Murai, Ryu Imamura, Kiyo-Aki Ishii, Hiroaki Takayama, Yukako Matsumoto, Natsumi Tajima-Shirasaki, Naoto Nagata, Ryogo Shimizu, Souma Yamanaka, Atsushi Abe, Hitoshi Omura, Kazunori Kawaguchi, Hikari Okada, Taro Yamashita, Tomoki Yoshikawa, Kazuhiro Takimoto, Motoko Taharaguchi, Shogo Takatsuka, Yoshitsugu Miyazaki, Toshikatsu Tamai, Yamato Tanabe, Makoto Kurachi, Yasuhiko Yamamoto, Shuichi Kaneko, Kunio Matsumoto, Toshinari Takamura, Masao Honda
Summary: This study reveals that leukocyte cell-derived chemotaxin 2 (LECT2) promotes RIG-I-mediated innate immune response and inhibits lymphocytic choriomeningitis virus replication by preventing RIG-I degradation. It also uncovers the crosstalk between LECT2-MET and HGF-MET signaling pathways, suggesting the therapeutic potential of targeting LECT2 in infectious diseases and cancer.
NATURE COMMUNICATIONS
(2022)
Article
Nutrition & Dietetics
Hitoshi Ando, Naoto Nagata, Takashi Hosono, Nazmul Hasan, Jun-ichi Morishige, Takiko Daikoku, Yoshiko Maida, Masanori Ono, Tomoko Fujiwara, Hiroshi Fujiwara
Summary: This study aimed to investigate whether habitual feeding time affects the daily rhythm of core body temperature (CBT). The results showed that the effect of habitual feeding time on CBT lasts until the following day and may be mediated by both UCP1-dependent and -independent mechanisms.
FRONTIERS IN NUTRITION
(2022)
Review
Biochemistry & Molecular Biology
Masanori Ono, Hitoshi Ando, Takiko Daikoku, Tomoko Fujiwara, Michihiro Mieda, Yasunari Mizumoto, Takashi Iizuka, Kyosuke Kagami, Takashi Hosono, Satoshi Nomura, Natsumi Toyoda, Naomi Sekizuka-Kagami, Yoshiko Maida, Naoaki Kuji, Hirotaka Nishi, Hiroshi Fujiwara
Summary: The circadian rhythm, controlled by clock genes, is crucial for reproduction. In the mouse uterus, the oscillation of circadian clock gene has been observed. CLOCK-BMAL1 heterodimer promotes the transcription of Per1/2 and Cry1/2 genes by binding to their promoters' E-box sequences. The endometrial clock plays an important role in pregnancy, and disruptions in the uterine clock can lead to complications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Hironao Okubo, Hitoshi Ando, Yusuke Takasaki, Eisuke Nakadera, Yuka Fukuo, Shuichiro Shiina, Kenichi Ikejima
Summary: This study investigated the impact of cabozantinib exposure on proteinuria and muscle toxicity in Japanese patients with unresectable hepatocellular carcinoma. The findings suggest that cabozantinib treatment can lead to proteinuria and muscle toxicity, which can be predicted by measuring serum creatine kinase and aldolase levels.
Review
Medicine, General & Internal
Naoto Nagata, Guanliang Chen, Liang Xu, Hitoshi Ando
Summary: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, and hepatic inflammation plays a crucial role in its development. Chemokines, especially CCL2 and CCL5, are important in inducing insulin resistance, steatosis, inflammation, and fibrosis in NAFLD. Cenicriviroc (CVC), a dual antagonist of chemokine receptors, has shown potential as a therapeutic approach for NASH-associated liver fibrosis.
MEDICINA-LITHUANIA
(2022)
Article
Medicine, General & Internal
Nazmul Hasan, Koki Sugimoto, Koki Yamada, Jun-ichi Morishige, Kentaro Ushijima, Akio Fujimura, Naoto Nagata, Hitoshi Ando
Summary: This study investigated whether chronic treatment with the antidiabetic agent metformin impairs circadian clocks, especially if given at an inappropriate time. The results showed that chronic treatment with metformin does not disrupt circadian clock gene expression in peripheral tissues and affects hepatic AMPK activation rhythm in diabetic mice.
MEDICINA-LITHUANIA
(2022)