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miR-378 Activates the Pyruvate-PEP Futile Cycle and Enhances Lipolysis to Ameliorate Obesity in Mice.
- 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.
- Subjects :
- Adipose Tissue metabolism
Animals
Diet, High-Fat
Glucose metabolism
Humans
Lipolysis genetics
Mice
Mice, Transgenic
MicroRNAs administration & dosage
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Obesity pathology
Obesity therapy
Oligoribonucleotides administration & dosage
Oligoribonucleotides genetics
Pyruvic Acid metabolism
Thermogenesis
Energy Metabolism genetics
MicroRNAs genetics
Obesity genetics
Substrate Cycling genetics
Subjects
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