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

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.

• Authors: Jie Wen, Jiangming Deng, Ting Xiao, Yu Liu, Wen Meng
• Journal: Journal of genetics and genomics = Yi chuan xue bao (J Genet Genomics) Vol. 50 Issue 1 Pg. 20-26 (01 2023) ISSN: 1673-8527 [Print] China
• PMID: 35550871 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Chemical References

• PPAR gamma
• TOR Serine-Threonine Kinases
• MicroRNAs

Topics

• Animals
• Mice
• PPAR gamma (genetics, metabolism, pharmacology)
• Adipose Tissue, White (metabolism, pathology)
• Signal Transduction
• Obesity (genetics, metabolism)
• TOR Serine-Threonine Kinases (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• Brain (metabolism)