- Pathophysiology
- Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
-
Inês Sousa-Lima, Hyun Jeong Kim, John Jones, Young-Bum Kim
-
Diabetes Metab J. 2021;45(5):655-674. Published online September 30, 2021
-
DOI: https://doi.org/10.4093/dmj.2021.0197
-
-
6,790
View
-
180
Download
-
8
Web of Science
-
7
Crossref
-
Graphical Abstract
Abstract
PDFPubReader ePub
- Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.
-
Citations
Citations to this article as recorded by
- THE ROLE OF N6-METHYLADENOSINE METHYLTRANSFERASE RBM15 IN NONALCOHOLIC FATTY LIVER DISEASE
Shiqing Li, Shengyi Lian, Wei Cheng, Tao Zhang, Xiaobing Gong Shock.2024; 61(2): 311. CrossRef - Exploring the potential of drug repurposing for liver diseases: A comprehensive study
Fares E.M. Ali, Mustafa Ahmed Abdel-Reheim, Emad H.M. Hassanein, Mostafa K. Abd El-Aziz, Hanan S. Althagafy, Khalid S.A. Badran Life Sciences.2024; 347: 122642. CrossRef - Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice
Xixi Lin, Like Wang, Xiaojie Lu, Yuanyuan Zhang, Rongying Zheng, Ruijie Chen, Weixi Zhang Respiratory Research.2023;[Epub] CrossRef - Selectivity matters: selective ROCK2 inhibitor ameliorates established liver fibrosis via targeting inflammation, fibrosis, and metabolism
Alexandra Zanin-Zhorov, Wei Chen, Julien Moretti, Melanie S. Nyuydzefe, Iris Zhorov, Rashmi Munshi, Malavika Ghosh, Cindy Serdjebi, Kelli MacDonald, Bruce R. Blazar, Melissa Palmer, Samuel D. Waksal Communications Biology.2023;[Epub] CrossRef - Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis
Lei Wei, Jianjian Shi Frontiers in Endocrinology.2022;[Epub] CrossRef - Paeoniflorin alleviates liver injury in hypercholesterolemic rats through the ROCK/AMPK pathway
Tong Liu, Ning Zhang, Lingya Kong, Sijie Chu, Ting Zhang, Guangdi Yan, Donglai Ma, Jun Dai, Zhihong Ma Frontiers in Pharmacology.2022;[Epub] CrossRef - Fasudil Increased the Sensitivity to Gefitinib in NSCLC by Decreasing Intracellular Lipid Accumulation
Tingting Liao, Jingjing Deng, Wenjuan Chen, Juanjuan Xu, Guanghai Yang, Mei Zhou, Zhilei Lv, Sufei Wang, Siwei Song, Xueyun Tan, Zhengrong Yin, Yumei Li, Yang Jin Cancers.2022; 14(19): 4709. CrossRef
|