Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting β3-adrenergic

Sisi Chen1,2, Xiaohan Mei1, Amelia Yin3,4

  • 1Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia, USA.

Insights

Response gene to complement 32 (RGC-32) deficiency enhances thermogenic gene expression in adipose tissues. RGC-32 suppresses this by inhibiting the PI3K/Akt pathway, leading to increased beta3-adrenergic receptor and mTORC1 activity.

Area of Science:

  • Metabolism and Endocrinology
  • Cellular Biology
  • Obesity Research

Background:

  • Response gene to complement 32 (RGC-32) deficiency protects against diet-induced obesity and boosts thermogenic gene expression.
  • The precise mechanisms by which RGC-32 influences thermogenic gene regulation in adipose tissue are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying RGC-32's regulation of thermogenic gene expression in adipose tissues.
  • To investigate the role of RGC-32 in cold-induced adipose tissue browning and its impact on key signaling pathways.

Main Methods:

  • Utilized mouse models with RGC-32 deficiency (Rgc32-/-) and cold exposure.
  • Performed RNA sequencing on inguinal white adipose tissue (iWAT).
  • Analyzed PI3K/Akt signaling, beta3-adrenergic receptor (β3-AR) expression, and mammalian target of rapamycin complex 1 (mTORC1) activity.

Main Results:

  • RGC-32 expression decreased during cold-induced WAT browning.
  • Rgc32-/- mice exhibited increased thermogenic gene expression in iWAT and brown adipose tissue (BAT).
  • RGC-32 deficiency led to decreased Akt phosphorylation, increased β3-AR expression, and enhanced mTORC1 activity, which were crucial for thermogenesis.

Conclusions:

  • RGC-32 suppresses adipose tissue thermogenic gene expression.
  • This suppression occurs via down-regulation of β3-AR expression and mTORC1 activity through a PI3K/Akt-dependent pathway.
  • Targeting RGC-32 may offer a novel strategy for managing obesity and metabolic disorders.

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