Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1a/ERRa.

Authors: Yan, Ming  Audet-Walsh, √Čtienne  Manteghi, Sanaz  Dufour, Catherine Rosa  Walker, Benjamin  Baba, Masaya  St-Pierre, Julie  Gigu√®re, Vincent  Pause, Arnim 
Citation: Yan M, etal., Genes Dev. 2016 May 1;30(9):1034-46. doi: 10.1101/gad.281410.116.
Pubmed: (View Article at PubMed) PMID:27151976
DOI: Full-text: DOI:10.1101/gad.281410.116

The tumor suppressor folliculin (FLCN) forms a repressor complex with AMP-activated protein kinase (AMPK). Given that AMPK is a master regulator of cellular energy homeostasis, we generated an adipose-specific Flcn (Adipoq-FLCN) knockout mouse model to investigate the role of FLCN in energy metabolism. We show that loss of FLCN results in a complete metabolic reprogramming of adipose tissues, resulting in enhanced oxidative metabolism. Adipoq-FLCN knockout mice exhibit increased energy expenditure and are protected from high-fat diet (HFD)-induced obesity. Importantly, FLCN ablation leads to chronic hyperactivation of AMPK, which in turns induces and activates two key transcriptional regulators of cellular metabolism, proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) and estrogen-related receptor α (ERRα). Together, the AMPK/PGC-1α/ERRα molecular axis positively modulates the expression of metabolic genes to promote mitochondrial biogenesis and activity. In addition, mitochondrial uncoupling proteins as well as other markers of brown fat are up-regulated in both white and brown FLCN-null adipose tissues, underlying the increased resistance of Adipoq-FLCN knockout mice to cold exposure. These findings identify a key role of FLCN as a negative regulator of mitochondrial function and identify a novel molecular pathway involved in the browning of white adipocytes and the activity of brown fat.


Gene Ontology Annotations
Objects Annotated

Additional Information

RGD Object Information
RGD ID: 13673872
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.