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


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.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC4816830 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Zhang Yong Y   Li Changyin C   Li Hu H   Song Yipeng Y   Zhao Yixia Y   Zhai Lili L   Wang Haixia H   Zhong Ran R   Tang Huiru H   Zhu Dahai D  

EBioMedicine 20160311


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 futi  ...[more]

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