Format

Send to

Choose Destination
See comment in PubMed Commons below
EMBO Rep. 2017 May 24. pii: e201643827. doi: 10.15252/embr.201643827. [Epub ahead of print]

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

Author information

1
Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
2
Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
3
Biochemistry Department, Boston University School of Medicine, Boston, MA, USA.
4
Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
5
Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
6
Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA mliesa@mednet.ucla.edu oshirihai@mednet.ucla.edu.
7
Department of Clinical Biochemistry, School of Medicine, Ben Gurion University, Beer-Sheva, Israel.

Abstract

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.

KEYWORDS:

Mitofusin 2; brown adipose tissue; insulin resistance; obesity; thermogenesis

PMID:
28539390
DOI:
10.15252/embr.201643827
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center