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Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1
Rho-kinase 1 (ROCK1) has been implicated in diverse metabolic functions throughout the body, with promising evidence identifying ROCK1 as a therapeutic target in diabetes and obesity. Considering these metabolic roles, several pharmacological inhibitors have been developed to elucidate the mechanism...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901932/ https://www.ncbi.nlm.nih.gov/pubmed/33633690 http://dx.doi.org/10.3389/fendo.2020.622581 |
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author | Landry, Taylor Shookster, Daniel Huang, Hu |
author_facet | Landry, Taylor Shookster, Daniel Huang, Hu |
author_sort | Landry, Taylor |
collection | PubMed |
description | Rho-kinase 1 (ROCK1) has been implicated in diverse metabolic functions throughout the body, with promising evidence identifying ROCK1 as a therapeutic target in diabetes and obesity. Considering these metabolic roles, several pharmacological inhibitors have been developed to elucidate the mechanisms underlying ROCK1 function. Y27632 and fasudil are two common ROCK1 inhibitors; however, they have varying non-specific selectivity to inhibit other AGC kinase subfamily members and whole-body pharmacological approaches lack tissue-specific insight. As a result, interpretation of studies with these inhibitors is difficult, and alternative approaches are needed to elucidate ROCK1’s tissue specific metabolic functions. Fortunately, recent technological advances utilizing molecular carriers or genetic manipulation have facilitated discovery of ROCK1’s tissue-specific mechanisms of action. In this article, we review the tissue-specific roles of ROCK1 in the regulation of energy balance and substrate utilization. We highlight prominent metabolic roles in liver, adipose, and skeletal muscle, in which ROCK1 regulates energy expenditure, glucose uptake, and lipid metabolism via inhibition of AMPK2α and paradoxical modulation of insulin signaling. Compared to ROCK1’s roles in peripheral tissues, we also describe contradictory functions of ROCK1 in the hypothalamus to increase energy expenditure and decrease food intake via leptin signaling. Furthermore, dysregulated ROCK1 activity in either of these tissues results in metabolic disease phenotypes. Overall, tissue-specific approaches have made great strides in deciphering the many critical metabolic functions of ROCK1 and, ultimately, may facilitate the development of novel treatments for metabolic disorders. |
format | Online Article Text |
id | pubmed-7901932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79019322021-02-24 Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1 Landry, Taylor Shookster, Daniel Huang, Hu Front Endocrinol (Lausanne) Endocrinology Rho-kinase 1 (ROCK1) has been implicated in diverse metabolic functions throughout the body, with promising evidence identifying ROCK1 as a therapeutic target in diabetes and obesity. Considering these metabolic roles, several pharmacological inhibitors have been developed to elucidate the mechanisms underlying ROCK1 function. Y27632 and fasudil are two common ROCK1 inhibitors; however, they have varying non-specific selectivity to inhibit other AGC kinase subfamily members and whole-body pharmacological approaches lack tissue-specific insight. As a result, interpretation of studies with these inhibitors is difficult, and alternative approaches are needed to elucidate ROCK1’s tissue specific metabolic functions. Fortunately, recent technological advances utilizing molecular carriers or genetic manipulation have facilitated discovery of ROCK1’s tissue-specific mechanisms of action. In this article, we review the tissue-specific roles of ROCK1 in the regulation of energy balance and substrate utilization. We highlight prominent metabolic roles in liver, adipose, and skeletal muscle, in which ROCK1 regulates energy expenditure, glucose uptake, and lipid metabolism via inhibition of AMPK2α and paradoxical modulation of insulin signaling. Compared to ROCK1’s roles in peripheral tissues, we also describe contradictory functions of ROCK1 in the hypothalamus to increase energy expenditure and decrease food intake via leptin signaling. Furthermore, dysregulated ROCK1 activity in either of these tissues results in metabolic disease phenotypes. Overall, tissue-specific approaches have made great strides in deciphering the many critical metabolic functions of ROCK1 and, ultimately, may facilitate the development of novel treatments for metabolic disorders. Frontiers Media S.A. 2021-02-09 /pmc/articles/PMC7901932/ /pubmed/33633690 http://dx.doi.org/10.3389/fendo.2020.622581 Text en Copyright © 2021 Landry, Shookster and Huang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Landry, Taylor Shookster, Daniel Huang, Hu Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1 |
title | Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1 |
title_full | Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1 |
title_fullStr | Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1 |
title_full_unstemmed | Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1 |
title_short | Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1 |
title_sort | tissue-specific approaches reveal diverse metabolic functions of rho-kinase 1 |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901932/ https://www.ncbi.nlm.nih.gov/pubmed/33633690 http://dx.doi.org/10.3389/fendo.2020.622581 |
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