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Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling
Insulin signaling is mediated via a network of protein phosphorylation. Dysregulation of this network is central to obesity, type 2 diabetes and metabolic syndrome. Here we investigate the role of phosphatase binding protein Alpha4 (α4) that is essential for the serine/threonine protein phosphatase...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568526/ https://www.ncbi.nlm.nih.gov/pubmed/36241662 http://dx.doi.org/10.1038/s41467-022-33842-4 |
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author | Sakaguchi, Masaji Okagawa, Shota Okubo, Yuma Otsuka, Yuri Fukuda, Kazuki Igata, Motoyuki Kondo, Tatsuya Sato, Yoshifumi Yoshizawa, Tatsuya Fukuda, Takaichi Yamagata, Kazuya Cai, Weikang Tseng, Yu-Hua Sakaguchi, Nobuo Kahn, C. Ronald Araki, Eiichi |
author_facet | Sakaguchi, Masaji Okagawa, Shota Okubo, Yuma Otsuka, Yuri Fukuda, Kazuki Igata, Motoyuki Kondo, Tatsuya Sato, Yoshifumi Yoshizawa, Tatsuya Fukuda, Takaichi Yamagata, Kazuya Cai, Weikang Tseng, Yu-Hua Sakaguchi, Nobuo Kahn, C. Ronald Araki, Eiichi |
author_sort | Sakaguchi, Masaji |
collection | PubMed |
description | Insulin signaling is mediated via a network of protein phosphorylation. Dysregulation of this network is central to obesity, type 2 diabetes and metabolic syndrome. Here we investigate the role of phosphatase binding protein Alpha4 (α4) that is essential for the serine/threonine protein phosphatase 2A (PP2A) in insulin action/resistance in adipocytes. Unexpectedly, adipocyte-specific inactivation of α4 impairs insulin-induced Akt-mediated serine/threonine phosphorylation despite a decrease in the protein phosphatase 2A (PP2A) levels. Interestingly, loss of α4 also reduces insulin-induced insulin receptor tyrosine phosphorylation. This occurs through decreased association of α4 with Y-box protein 1, resulting in the enhancement of the tyrosine phosphatase protein tyrosine phosphatase 1B (PTP1B) expression. Moreover, adipocyte-specific knockout of α4 in male mice results in impaired adipogenesis and altered mitochondrial oxidation leading to increased inflammation, systemic insulin resistance, hepatosteatosis, islet hyperplasia, and impaired thermogenesis. Thus, the α4 /Y-box protein 1(YBX1)-mediated pathway of insulin receptor signaling is involved in maintaining insulin sensitivity, normal adipose tissue homeostasis and systemic metabolism. |
format | Online Article Text |
id | pubmed-9568526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95685262022-10-16 Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling Sakaguchi, Masaji Okagawa, Shota Okubo, Yuma Otsuka, Yuri Fukuda, Kazuki Igata, Motoyuki Kondo, Tatsuya Sato, Yoshifumi Yoshizawa, Tatsuya Fukuda, Takaichi Yamagata, Kazuya Cai, Weikang Tseng, Yu-Hua Sakaguchi, Nobuo Kahn, C. Ronald Araki, Eiichi Nat Commun Article Insulin signaling is mediated via a network of protein phosphorylation. Dysregulation of this network is central to obesity, type 2 diabetes and metabolic syndrome. Here we investigate the role of phosphatase binding protein Alpha4 (α4) that is essential for the serine/threonine protein phosphatase 2A (PP2A) in insulin action/resistance in adipocytes. Unexpectedly, adipocyte-specific inactivation of α4 impairs insulin-induced Akt-mediated serine/threonine phosphorylation despite a decrease in the protein phosphatase 2A (PP2A) levels. Interestingly, loss of α4 also reduces insulin-induced insulin receptor tyrosine phosphorylation. This occurs through decreased association of α4 with Y-box protein 1, resulting in the enhancement of the tyrosine phosphatase protein tyrosine phosphatase 1B (PTP1B) expression. Moreover, adipocyte-specific knockout of α4 in male mice results in impaired adipogenesis and altered mitochondrial oxidation leading to increased inflammation, systemic insulin resistance, hepatosteatosis, islet hyperplasia, and impaired thermogenesis. Thus, the α4 /Y-box protein 1(YBX1)-mediated pathway of insulin receptor signaling is involved in maintaining insulin sensitivity, normal adipose tissue homeostasis and systemic metabolism. Nature Publishing Group UK 2022-10-14 /pmc/articles/PMC9568526/ /pubmed/36241662 http://dx.doi.org/10.1038/s41467-022-33842-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sakaguchi, Masaji Okagawa, Shota Okubo, Yuma Otsuka, Yuri Fukuda, Kazuki Igata, Motoyuki Kondo, Tatsuya Sato, Yoshifumi Yoshizawa, Tatsuya Fukuda, Takaichi Yamagata, Kazuya Cai, Weikang Tseng, Yu-Hua Sakaguchi, Nobuo Kahn, C. Ronald Araki, Eiichi Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling |
title | Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling |
title_full | Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling |
title_fullStr | Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling |
title_full_unstemmed | Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling |
title_short | Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling |
title_sort | phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568526/ https://www.ncbi.nlm.nih.gov/pubmed/36241662 http://dx.doi.org/10.1038/s41467-022-33842-4 |
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