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

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)...

Full description

Saved in:
Bibliographic Details
Published in:Journal of genetics and genomics 2023-01, Vol.50 (1), p.20-26
Main Authors: Wen, Jie, Deng, Jiangming, Xiao, Ting, Liu, Yu, Meng, Wen
Format: Article
Language:English
Subjects:
Adipose tissue
Adipose Tissue, White - metabolism
Adipose Tissue, White - pathology
Animals
Brain - metabolism
cAMP/PPARγ pathway
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
miR-182-5p
Obesity - genetics
Obesity - metabolism
PPAR gamma - genetics
PPAR gamma - metabolism
PPAR gamma - pharmacology
Rheb
Signal Transduction
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
White adipocytes
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1673-8527
DOI:10.1016/j.jgg.2022.04.013