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Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis
The normal function of skeletal muscle and adipose tissue ensures whole-body glucose homeostasis. Ca(2+) release channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) plays a vital role in regulating diet-induced obesity and disorders, but its functions in peripheral tissue regulating glucose home...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998023/ https://www.ncbi.nlm.nih.gov/pubmed/36894534 http://dx.doi.org/10.1038/s41420-023-01389-y |
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author | Zhang, Xin Wang, Lu Wang, Yubo He, Linjuan Xu, Doudou Yan, Enfa Guo, Jianxin Ma, Chenghong Zhang, Pengguang Yin, Jingdong |
author_facet | Zhang, Xin Wang, Lu Wang, Yubo He, Linjuan Xu, Doudou Yan, Enfa Guo, Jianxin Ma, Chenghong Zhang, Pengguang Yin, Jingdong |
author_sort | Zhang, Xin |
collection | PubMed |
description | The normal function of skeletal muscle and adipose tissue ensures whole-body glucose homeostasis. Ca(2+) release channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) plays a vital role in regulating diet-induced obesity and disorders, but its functions in peripheral tissue regulating glucose homeostasis remain unexplored. In this study, mice with Ip3r1 specific knockout in skeletal muscle or adipocytes were used for investigating the mediatory role of IP3R1 on whole-body glucose homeostasis under normal or high-fat diet. We reported that IP3R1 expression levels were increased in the white adipose tissue and skeletal muscle of diet-induced obese mice. Ip3r1 knockout in skeletal muscle improved glucose tolerance and insulin sensitivity of mice on a normal chow diet, but worsened insulin resistance in diet-induced obese mice. These changes were associated with the reduced muscle weight and compromised Akt signaling activation. Importantly, Ip3r1 deletion in adipocytes protected mice from diet-induced obesity and glucose intolerance, mainly due to the enhanced lipolysis and AMPK signaling pathway in the visceral fat. In conclusion, our study demonstrates that IP3R1 in skeletal muscle and adipocytes exerts divergent effects on systemic glucose homeostasis, and characterizes adipocyte IP3R1 as a promising target for treating obesity and type 2 diabetes. |
format | Online Article Text |
id | pubmed-9998023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99980232023-03-10 Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis Zhang, Xin Wang, Lu Wang, Yubo He, Linjuan Xu, Doudou Yan, Enfa Guo, Jianxin Ma, Chenghong Zhang, Pengguang Yin, Jingdong Cell Death Discov Article The normal function of skeletal muscle and adipose tissue ensures whole-body glucose homeostasis. Ca(2+) release channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) plays a vital role in regulating diet-induced obesity and disorders, but its functions in peripheral tissue regulating glucose homeostasis remain unexplored. In this study, mice with Ip3r1 specific knockout in skeletal muscle or adipocytes were used for investigating the mediatory role of IP3R1 on whole-body glucose homeostasis under normal or high-fat diet. We reported that IP3R1 expression levels were increased in the white adipose tissue and skeletal muscle of diet-induced obese mice. Ip3r1 knockout in skeletal muscle improved glucose tolerance and insulin sensitivity of mice on a normal chow diet, but worsened insulin resistance in diet-induced obese mice. These changes were associated with the reduced muscle weight and compromised Akt signaling activation. Importantly, Ip3r1 deletion in adipocytes protected mice from diet-induced obesity and glucose intolerance, mainly due to the enhanced lipolysis and AMPK signaling pathway in the visceral fat. In conclusion, our study demonstrates that IP3R1 in skeletal muscle and adipocytes exerts divergent effects on systemic glucose homeostasis, and characterizes adipocyte IP3R1 as a promising target for treating obesity and type 2 diabetes. Nature Publishing Group UK 2023-03-09 /pmc/articles/PMC9998023/ /pubmed/36894534 http://dx.doi.org/10.1038/s41420-023-01389-y Text en © The Author(s) 2023 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 Zhang, Xin Wang, Lu Wang, Yubo He, Linjuan Xu, Doudou Yan, Enfa Guo, Jianxin Ma, Chenghong Zhang, Pengguang Yin, Jingdong Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis |
title | Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis |
title_full | Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis |
title_fullStr | Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis |
title_full_unstemmed | Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis |
title_short | Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis |
title_sort | lack of adipocyte ip3r1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998023/ https://www.ncbi.nlm.nih.gov/pubmed/36894534 http://dx.doi.org/10.1038/s41420-023-01389-y |
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