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.

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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