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

Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis.

Authors: Mahdaviani, Kiana  Benador, Ilan Y  Su, Shi  Gharakhanian, Raffi A  Stiles, Linsey  Trudeau, Kyle M  Cardamone, Maria  EnrĂ­quez-Zarralanga, Violeta  Ritou, Eleni  Aprahamian, Tamar  Oliveira, Marcus F  Corkey, Barbara E  Perissi, Valentina  Liesa, Marc  Shirihai, Orian S 
Citation: Mahdaviani K, etal., EMBO Rep. 2017 Jul;18(7):1123-1138. doi: 10.15252/embr.201643827. Epub 2017 May 24.
Pubmed: (View Article at PubMed) PMID:28539390
DOI: Full-text: DOI:10.15252/embr.201643827

BAT-controlled thermogenic activity is thought to be required for its capacity to prevent the development of insulin resistance. This hypothesis predicts that mediators of thermogenesis may help prevent diet-induced insulin resistance. We report that the mitochondrial fusion protein Mitofusin 2 (Mfn2) in BAT is essential for cold-stimulated thermogenesis, but promotes insulin resistance in obese mice. Mfn2 deletion in mice through Ucp1-cre (BAT-Mfn2-KO) causes BAT lipohypertrophy and cold intolerance. Surprisingly however, deletion of Mfn2 in mice fed a high fat diet (HFD) results in improved insulin sensitivity and resistance to obesity, while impaired cold-stimulated thermogenesis is maintained. Improvement in insulin sensitivity is associated with a gender-specific remodeling of BAT mitochondrial function. In females, BAT mitochondria increase their efficiency for ATP-synthesizing fat oxidation, whereas in BAT from males, complex I-driven respiration is decreased and glycolytic capacity is increased. Thus, BAT adaptation to obesity is regulated by Mfn2 and with BAT-Mfn2 absent, BAT contribution to prevention of insulin resistance is independent and inversely correlated to whole-body cold-stimulated thermogenesis.


Gene Ontology Annotations
Objects Annotated

Additional Information

RGD Object Information
RGD ID: 13673759
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.