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Updated: Feb 12, 2026

Three-Dimensional Culture of Vascularized Thermogenic Adipose Tissue from Microvascular Fragments
Published on: February 3, 2023
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.
Abstract:
Our previous studies have shown that response gene to complement (RGC)-32 deficiency (Rgc32-/-) protects mice from diet-induced obesity and increases thermogenic gene expression in adipose tissues. However, the underlying mechanisms by which RGC-32 regulates thermogenic gene expression remain to be determined. In the present study, RGC-32 expression in white adipose tissue (WAT) was suppressed during cold exposure-induced WAT browning. Rgc32-/- significantly increased thermogenic gene expression in the differentiated stromal vascular fraction (SVF) of inguinal (i)WAT and interscapular brown adipose tissue (BAT). Rgc32-/- and cold exposure regulated a common set of genes in iWAT, as shown by RNA sequencing data. Pathway enrichment analyses showed that Rgc32-/- down-regulated PI3K/Akt signaling-related genes. Akt phosphorylation was also consistently decreased in Rgc32-/- iWAT, which led to an increase in β3-adrenergic receptor (β3-AR) expression and subsequent activation of mammalian target of rapamycin complex (mTORC)-1. β3-AR antagonist SR 59230A and mTORC1 inhibitor rapamycin blocked Rgc32-/--induced thermogenic gene expression in both iWAT and interscapular BAT. These results indicate that RGC-32 suppresses adipose tissue thermogenic gene expression through down-regulation of β3-AR expression and mTORC1 activity via a PI3K/Akt-dependent mechanism.-Chen, S., Mei, X., Yin, A., Yin, H., Cui, X.-B., Chen, S.-Y. Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting β3-adrenergic receptor/mTORC1 signaling.
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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