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.

Details

Title
MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance
Author
Li-Min, Wei 1 ; Rui-Ping, Sun 1 ; Dong, Tao 2 ; Liu, Jie 2 ; Chen, Ting 2 ; Zeng Bin 2 ; Jia-Han, Wu 2 ; Jun-yi, Luo 2 ; Jia-Jie, Sun 2 ; Qian-Yun, Xi 2 ; Yong-Liang, Zhang 2 

 South China Agricultural University, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou, China (GRID:grid.20561.30) (ISNI:0000 0000 9546 5767); Hainan Academy of Agricultural Sciences, Institute of Animal Science and Veterinary Medicine, Haikou, China (GRID:grid.464347.6) 
 South China Agricultural University, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou, China (GRID:grid.20561.30) (ISNI:0000 0000 9546 5767) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2473192438
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.