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Three-Dimensional Culture of Vascularized Thermogenic Adipose Tissue from Microvascular Fragments
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ERRγ Preserves Brown Fat Innate Thermogenic Activity.
Maryam Ahmadian1, Sihao Liu1, Shannon M Reilly2
1Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cell Reports
|March 15, 2018
Summary
Estrogen-related receptor gamma (ERRγ) is crucial for brown adipose tissue (BAT) identity and function. Loss of ERRγ impairs thermogenic capacity, highlighting its role in maintaining BAT for energy expenditure.
Area of Science:
- Metabolism
- Cell Biology
- Endocrinology
Background:
- Brown adipose tissue (BAT) generates heat by uncoupling mitochondrial electron transport through a specific gene network.
- The transcription factors responsible for initiating BAT's rapid adaptive thermogenic response remain largely unidentified.
Purpose of the Study:
- To identify innate transcription factors critical for maintaining brown adipose tissue identity and function.
- To elucidate the role of estrogen-related receptor gamma (ERRγ) in regulating BAT thermogenesis.
Main Methods:
- Investigated the expression of ERRγ in brown adipose tissue (BAT) versus white adipose tissue (WAT).
- Generated adipose-specific ERRγ knockout (ERRγKO) mice to assess its function in vivo.
- Analyzed transcriptional changes and thermogenic capacity in ERRγKO mice.
Main Results:
- Estrogen-related receptor gamma (ERRγ) is selectively expressed in BAT and drives a core thermogenic and oxidative gene network.
- ERRγKO mice exhibited significant downregulation of BAT-selective genes, leading to BAT "whitening" and impaired thermogenic capacity.
- ERRγKO mice were unable to survive acute cold challenges due to blunted thermogenesis.
Conclusions:
- Estrogen-related receptor gamma (ERRγ) is a critical factor for maintaining brown adipose tissue identity and its basal thermogenic state.
- ERRγ is essential for priming BAT to respond effectively to cold and metabolic challenges.
- Targeting ERRγ may offer therapeutic strategies for metabolic disorders related to energy expenditure.
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