Diabetes & Metabolism Journal

Sulwon Lecture 2020

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

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Graphical Abstract Abstract PDF PubReader 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

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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
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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
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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

Original Article

Lifesytle
Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women: Yun Kyung Jeon, Sang Soo Kim, Jong Ho Kim, Hyun Jeong Kim, Hyun Jun Kim, Jang Jun Park, Yuen Suk Cho, So Hee Joung, Ji Ryang Kim, Bo Hyun Kim, Sang Heon Song, In Joo Kim, Yong Ki Kim, Young-Bum Kim; Diabetes Metab J. 2020;44(1):103-112. Published online February 21, 2020; DOI: https://doi.org/10.4093/dmj.2018.0160

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155 Download
12 Web of Science
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Abstract PDF Supplementary Material PubReader

Background

Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.

Methods

Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.

Results

In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.

Conclusion

Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

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Liangying Hou, Qi Wang, Bei Pan, Rui Li, Yanfei Li, Juanjuan He, Tianzhu Qin, Liujiao Cao, Na Zhang, Changhao Cao, Long Ge, Kehu Yang
Diabetes/Metabolism Research and Reviews.2023;[Epub] CrossRef
Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials
Gina Wood, Emily Taylor, Vanessa Ng, Anna Murrell, Aditya Patil, Tom van der Touw, Mitch Wolden, Nick Andronicos, Neil A. Smart
Sports Medicine.2023; 53(4): 871. CrossRef
2023 update on Italian guidelines for the treatment of type 2 diabetes
Edoardo Mannucci, Riccardo Candido, Lina delle Monache, Marco Gallo, Andrea Giaccari, Maria Luisa Masini, Angela Mazzone, Gerardo Medea, Basilio Pintaudi, Giovanni Targher, Marina Trento, Giuseppe Turchetti, Valentina Lorenzoni, Matteo Monami
Acta Diabetologica.2023; 60(8): 1119. CrossRef
The Effect of Eight Weeks of Concurrent Training on Serum Levels of Paraxonase-1, Irisin, Lipid Profile, and Insulin Resistance in Men With Metabolic Syndrome
Seyed Amir Hosain Diba Hosaini, Morvarid Vafaee, Bahram Abedi
Hormozgan Medical Journal.2023; 27(1): 43. CrossRef
An Overview of the TRP-Oxidative Stress Axis in Metabolic Syndrome: Insights for Novel Therapeutic Approaches
Mizael C. Araújo, Suzany H. S. Soczek, Jaqueline P. Pontes, Leonardo A. C. Marques, Gabriela S. Santos, Gisele Simão, Laryssa R. Bueno, Daniele Maria-Ferreira, Marcelo N. Muscará, Elizabeth S. Fernandes
Cells.2022; 11(8): 1292. CrossRef
Effect of Yijinjing combined with elastic band exercise on muscle mass and function in middle-aged and elderly patients with prediabetes: A randomized controlled trial
Yunda Huang, Junhua Han, Qing Gu, Yanwei Cai, Jingyuan Li, Shasha Wang, Suijun Wang, Ru Wang, Xiangyun Liu
Frontiers in Medicine.2022;[Epub] CrossRef
Effect of combined aerobic and resistance exercise on blood pressure in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials
Huihui Xi, Yayu He, Yirou Niu, Xin Sui, Jun Zhang, Ruiting Zhu, Haiyan Xu, Shuang Zhang, Yang Li, Yuan Yuan, Lirong Guo
Experimental Gerontology.2021; 155: 111560. CrossRef
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Sangwan Jeon, Jiyoun Kim
International Journal of Environmental Research and Public Health.2020; 17(9): 3260. CrossRef
Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity
Ji A Seo, Min-Cheol Kang, Won-Mo Yang, Won Min Hwang, Sang Soo Kim, Soo Hyun Hong, Jee-In Heo, Achana Vijyakumar, Leandro Pereira de Moura, Aykut Uner, Hu Huang, Seung Hwan Lee, Inês S. Lima, Kyong Soo Park, Min Seon Kim, Yossi Dagon, Thomas E. Willnow, V
Nature Communications.2020;[Epub] CrossRef
Impact of Skeletal Muscle Mass on Metabolic Health
Gyuri Kim, Jae Hyeon Kim
Endocrinology and Metabolism.2020; 35(1): 1. CrossRef
Habitual Combined Exercise Protects against Age-Associated Decline in Vascular Function and Lipid Profiles in Elderly Postmenopausal Women
Elizabeth J. Pekas, John Shin, Won-Mok Son, Ronald J. Headid, Song-Young Park
International Journal of Environmental Research and Public Health.2020; 17(11): 3893. CrossRef

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