These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


PUBMED FOR HANDHELDS

Search MEDLINE/PubMed


  • Title: Adipocyte miR-200b/a/429 ablation in mice leads to high-fat-diet-induced obesity.
    Author: Tao C, Ren H, Xu P, Cheng J, Huang S, Zhou R, Mu Y, Yang S, Qi D, Wang Y, Li K.
    Journal: Oncotarget; 2016 Oct 18; 7(42):67796-67807. PubMed ID: 27655719.
    Abstract:
    Growing evidence demonstrates the important role of microRNAs (miRs) in regulating adipogenesis, obesity and insulin resistance. The miR-200b/a/429 cluster has been functionally characterized in mammalian reproduction; however, the potential role of the miR-200 family in adipocytes is poorly understood. The aim of our study was to investigate the physiological function of miR-200b/a/429 in the regulation of whole-body metabolism in terms of the activities and targets of this cluster in adipocytes. We generated adipocyte-specific miR-200b/a/429 knockout (ASKO) mice using a Cre-loxP system in which Cre expression was driven by the aP2 promoter. The ASKO and wild type (WT) littermate were fed a chow diet (CD) or high-fat-diet (HFD), and changes in body composition, metabolic parameters, energy homeostasis, glucose tolerance and insulin sensitivity were analyzed. The miR-200b/a/429 putative target genes were predicted and validated via luciferase reporter assays. We found that the HFD-fed ASKO mice gradually gained more body weight than the WT mice due to the increased adiposity. Decreased glucose tolerance and insulin sensitivity were also observed in the HFD-fed ASKO mice. Notably, the down-regulation of lipolysis-related genes and the decreased response to CL-316,243 stimulation in the HFD-fed ASKO mice suggested that these animals exhibited impaired lipolysis. In addition, the HFD-fed ASKO mice displayed impaired energy expenditure, indicating that the miR-200b/a/429 cluster is essential for developing adaptive responses to stressors such as HFD. For the first time, our studies demonstrated the essential role of miR-200b/a/429 in adipocytes in the regulation of HFD-induced whole-body metabolic changes.
    [Abstract] [Full Text] [Related] [New Search]