Back to Search Start Over

miR-378 Activates the Pyruvate-PEP Futile Cycle and Enhances Lipolysis to Ameliorate Obesity in Mice.

Authors :
Zhang Y
Li C
Li H
Song Y
Zhao Y
Zhai L
Wang H
Zhong R
Tang H
Zhu D
Source :
EBioMedicine [EBioMedicine] 2016 Mar 11; Vol. 5, pp. 93-104. Date of Electronic Publication: 2016 Mar 11 (Print Publication: 2016).
Publication Year :
2016

Abstract

Obesity has been linked to many health problems, such as diabetes. However, there is no drug that effectively treats obesity. Here, we reveal that miR-378 transgenic mice display reduced fat mass, enhanced lipolysis, and increased energy expenditure. Notably, administering AgomiR-378 prevents and ameliorates obesity in mice. We also found that the energy deficiency seen in miR-378 transgenic mice was due to impaired glucose metabolism. This impairment was caused by an activated pyruvate-PEP futile cycle via the miR-378-Akt1-FoxO1-PEPCK pathway in skeletal muscle and enhanced lipolysis in adipose tissues mediated by miR-378-SCD1. Our findings demonstrate that activating the pyruvate-PEP futile cycle in skeletal muscle is the primary cause of elevated lipolysis in adipose tissues of miR-378 transgenic mice, and it helps orchestrate the crosstalk between muscle and fat to control energy homeostasis in mice. Thus, miR-378 may serve as a promising agent for preventing and treating obesity in humans.

Details

Language :
English
ISSN :
2352-3964
Volume :
5
Database :
MEDLINE
Journal :
EBioMedicine
Publication Type :
Academic Journal
Accession number :
27077116
Full Text :
https://doi.org/10.1016/j.ebiom.2016.01.035