MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance
Abstract 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 tha...
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doaj-049c57d96a494627bab4056c0d54b8582020-12-20T12:29:30ZengNature Publishing GroupScientific Reports2045-23222020-12-0110111010.1038/s41598-020-77714-7MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistanceLi-Min Wei0Rui-Ping Sun1Tao Dong2Jie Liu3Ting Chen4Bin Zeng5Jia-Han Wu6Jun-yi Luo7Jia-Jie Sun8Qian-Yun Xi9Yong-Liang Zhang10Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural UniversityAbstract 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.https://doi.org/10.1038/s41598-020-77714-7 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li-Min Wei Rui-Ping Sun Tao Dong Jie Liu Ting Chen Bin Zeng Jia-Han Wu Jun-yi Luo Jia-Jie Sun Qian-Yun Xi Yong-Liang Zhang |
spellingShingle |
Li-Min Wei Rui-Ping Sun Tao Dong Jie Liu Ting Chen Bin Zeng Jia-Han Wu Jun-yi Luo Jia-Jie Sun Qian-Yun Xi Yong-Liang Zhang MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance Scientific Reports |
author_facet |
Li-Min Wei Rui-Ping Sun Tao Dong Jie Liu Ting Chen Bin Zeng Jia-Han Wu Jun-yi Luo Jia-Jie Sun Qian-Yun Xi Yong-Liang Zhang |
author_sort |
Li-Min Wei |
title |
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_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_sort |
mir-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-12-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1038/s41598-020-77714-7 |
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