| First Author | Mahdaviani K | Year | 2017 |
| Journal | EMBO Rep | Volume | 18 |
| Issue | 7 | Pages | 1123-1138 |
| PubMed ID | 28539390 | Mgi Jnum | J:243572 |
| Mgi Id | MGI:5909151 | Doi | 10.15252/embr.201643827 |
| Citation | Mahdaviani K, et al. (2017) Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis. EMBO Rep 18(7):1123-1138 |
| abstractText | 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. |
