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MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance
Obese individuals are more susceptible to comorbidities than individuals of healthy weight, including cardiovascular disease and metabolic disorders. MicroRNAs are a class of small and noncoding RNAs that are implicated in the regulation of chronic human diseases. We previously reported that miR-125...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738482/ https://www.ncbi.nlm.nih.gov/pubmed/33319811 http://dx.doi.org/10.1038/s41598-020-77714-7 |
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author | Wei, Li-Min Sun, Rui-Ping Dong, Tao Liu, Jie Chen, Ting Zeng, Bin Wu, Jia-Han Luo, Jun-yi Sun, Jia-Jie Xi, Qian-Yun Zhang, Yong-Liang |
author_facet | Wei, Li-Min Sun, Rui-Ping Dong, Tao Liu, Jie Chen, Ting Zeng, Bin Wu, Jia-Han Luo, Jun-yi Sun, Jia-Jie Xi, Qian-Yun Zhang, Yong-Liang |
author_sort | Wei, Li-Min |
collection | PubMed |
description | Obese individuals are more susceptible to comorbidities than individuals of healthy weight, including cardiovascular disease and metabolic disorders. MicroRNAs are a class of small and noncoding RNAs that are implicated in the regulation of chronic human diseases. We previously reported that miR-125b plays a critical role in adipogenesis in vitro. However, the involvement of miR-125b-2 in fat metabolism in vivo remains unknown. In the present study, miR-125b-2 knockout mice were generated using CRISPR/CAS9 technology, resulting in mice with a 7 bp deletion in the seed sequence of miR-125b-2. MiR-125b-2 knockout increased the weight of liver tissue, epididymal white fat and inguinal white fat. MiR-125b-2 knockout also increased adipocyte volume in HFD-induced obese mice, while there were no significant differences in body weight and feed intake versus mice fed a normal diet. Additionally, qRT-PCR and western blot analysis revealed that the expression of the miR-125b-2 target gene SCD-1 and fat synthesis-associated genes, such as PPARγ and C/EBPα, were significantly up-regulated in miR-125b-2KO mice (P < 0.05). Moreover, miR-125b-2KO altered HFD-induced changes in glucose tolerance and insulin resistance. In conclusion, we show that miR-125b-2 is a novel potential target for regulating fat accumulation, and also a candidate target to develop novel treatment strategies for obesity and diabetes. |
format | Online Article Text |
id | pubmed-7738482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77384822020-12-17 MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance Wei, Li-Min Sun, Rui-Ping Dong, Tao Liu, Jie Chen, Ting Zeng, Bin Wu, Jia-Han Luo, Jun-yi Sun, Jia-Jie Xi, Qian-Yun Zhang, Yong-Liang Sci Rep Article Obese individuals are more susceptible to comorbidities than individuals of healthy weight, including cardiovascular disease and metabolic disorders. MicroRNAs are a class of small and noncoding RNAs that are implicated in the regulation of chronic human diseases. We previously reported that miR-125b plays a critical role in adipogenesis in vitro. However, the involvement of miR-125b-2 in fat metabolism in vivo remains unknown. In the present study, miR-125b-2 knockout mice were generated using CRISPR/CAS9 technology, resulting in mice with a 7 bp deletion in the seed sequence of miR-125b-2. MiR-125b-2 knockout increased the weight of liver tissue, epididymal white fat and inguinal white fat. MiR-125b-2 knockout also increased adipocyte volume in HFD-induced obese mice, while there were no significant differences in body weight and feed intake versus mice fed a normal diet. Additionally, qRT-PCR and western blot analysis revealed that the expression of the miR-125b-2 target gene SCD-1 and fat synthesis-associated genes, such as PPARγ and C/EBPα, were significantly up-regulated in miR-125b-2KO mice (P < 0.05). Moreover, miR-125b-2KO altered HFD-induced changes in glucose tolerance and insulin resistance. In conclusion, we show that miR-125b-2 is a novel potential target for regulating fat accumulation, and also a candidate target to develop novel treatment strategies for obesity and diabetes. Nature Publishing Group UK 2020-12-15 /pmc/articles/PMC7738482/ /pubmed/33319811 http://dx.doi.org/10.1038/s41598-020-77714-7 Text en © The Author(s) 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wei, Li-Min Sun, Rui-Ping Dong, Tao Liu, Jie Chen, Ting Zeng, Bin Wu, Jia-Han Luo, Jun-yi Sun, Jia-Jie Xi, Qian-Yun Zhang, Yong-Liang MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance |
title | MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance |
title_full | MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance |
title_fullStr | MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance |
title_full_unstemmed | MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance |
title_short | MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance |
title_sort | mir-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738482/ https://www.ncbi.nlm.nih.gov/pubmed/33319811 http://dx.doi.org/10.1038/s41598-020-77714-7 |
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