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Updated: Sep 23, 2025

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
Adipose Rheb deficiency promotes miR-182-5p expression via the cAMP/PPARγ signaling pathway
Jie Wen1, Jiangming Deng1, Ting Xiao1
1Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China; Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
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.
Insights
Ras homolog enriched in brain (Rheb) regulates miR-182-5p in adipocytes via a mTOR-independent pathway. This mechanism promotes thermogenesis and energy expenditure, offering insights into obesity pathogenesis.
Area of Science:
- Molecular Biology
- Metabolic Research
- Adipocyte Biology
Background:
- MicroRNA (miRNA) dysregulation in adipocytes is implicated in obesity.
- Signaling pathways controlling miRNA production in adipose tissue are not fully understood.
Purpose of the Study:
- To elucidate the signaling mechanisms regulating miRNA production in adipose tissue.
- To investigate the role of Ras homolog enriched in brain (Rheb) in adipocyte miRNA expression.
Main Methods:
- Generated adipose tissue-specific Rheb knockout mice.
- Utilized primary subcutaneous white adipocytes for in vitro studies.
- Assessed miRNA levels and signaling pathway activation (mTOR, cAMP/PPARγ).
Main Results:
- Adipose tissue-specific Rheb knockout increased miR-182-5p levels in white adipose tissue.
- mTOR inhibition did not affect miR-182-5p levels, indicating a mTOR-independent mechanism.
- Rheb ablation activated the cAMP/PPARγ pathway, and PPARγ agonism upregulated miR-182-5p.
Conclusions:
- Rheb regulates miR-182-5p expression in adipocytes through a novel mTOR-independent pathway involving cAMP/PPARγ.
- This Rheb-mediated regulation of miR-182-5p promotes beige fat development, thermogenesis, and energy expenditure.
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