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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...

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Autores principales: Landry, Taylor, Shookster, Daniel, Huang, Hu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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