Adipose Rheb deficiency promotes miR-182-5p expression via the cAMP/PPARγ signaling pathway

Jie Wen; Jiangming Deng; Ting Xiao; Yu Liu; Wen Meng

doi:10.1016/j.jgg.2022.04.013

Volume 50 Issue 1

Jan. 2023

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Adipose Rheb deficiency promotes miR-182-5p expression via the cAMP/PPARγ signaling pathway

doi: 10.1016/j.jgg.2022.04.013

Jie Wen^a,b,
Jiangming Deng^a,b,
Ting Xiao^a,b,
Yu Liu^a,
Wen Meng^a,b

a. Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China;
b. Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China

Funds:

This work was partially supported by grants 82170886 and 81800758 from the National Nature Science Foundation of China and partially supported by the Fundamental Research Funds for the Central Universities of Central South University (2021zzts1048).

Received Date: 2022-02-11
Accepted Date: 2022-04-25
Rev Recd Date: 2022-04-25
Publish Date: 2023-01-28

Abstract

Abstract

Dysregulation of microRNAs (miRNAs) in adipocytes plays a critical role in the pathogenesis of obesity. However, the signaling mechanisms regulating miRNAs production in adipose tissue remain largely unclear. Here, we show that adipose tissue-specific knockout of Ras homolog enriched in brain (Rheb), a direct upstream activator of mTOR, increases miR-182-5p level in mouse subcutaneous white adipose tissues. Interestingly, the inhibition of mTOR signaling by rapamycin has no effect on miR-182-5p level in primary subcutaneous white adipocytes, suggesting the presence of a mTOR-independent mechanism regulating Rheb-mediated miR-182-5p expression. Consistent with this view, Rheb-ablation activates the cAMP/PPARγ signaling pathway. In addition, treatment of white adipocytes with pioglitazone, a PPARγ agonist, dramatically upregulates miR-182-5p levels. Our study reveals a unique mechanism by which Rheb regulates miR-182-5p in adipocytes. Given that increasing miR-182-5p in adipose tissue promotes beige fat development, our study also suggests a unique mechanism by which Rheb promotes thermogenesis and energy expenditure.
- Rheb,
- miR-182-5p,
- White adipocytes,
- cAMP/PPARγ pathway,
- Adipose tissue

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References(33)

References

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