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EMBO J. 2017 Jun 1;36(11):1543-1558. doi: 10.15252/embj.201694914. Epub 2017 Mar 27.

Mfn2 is critical for brown adipose tissue thermogenic function.

Author information

1
Nestlé Institute of Health Sciences, Lausanne, Switzerland.
2
School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
3
Center of PhenoGenomics (CPG), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
4
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
5
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
6
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
7
Nestlé Institute of Health Sciences, Lausanne, Switzerland carlos.cantoalvarez@rd.nestle.com.

Abstract

Mitochondrial fusion and fission events, collectively known as mitochondrial dynamics, act as quality control mechanisms to ensure mitochondrial function and fine-tune cellular bioenergetics. Defective mitofusin 2 (Mfn2) expression and enhanced mitochondrial fission in skeletal muscle are hallmarks of insulin-resistant states. Interestingly, Mfn2 is highly expressed in brown adipose tissue (BAT), yet its role remains unexplored. Using adipose-specific Mfn2 knockout (Mfn2-adKO) mice, we demonstrate that Mfn2, but not Mfn1, deficiency in BAT leads to a profound BAT dysfunction, associated with impaired respiratory capacity and a blunted response to adrenergic stimuli. Importantly, Mfn2 directly interacts with perilipin 1, facilitating the interaction between the mitochondria and the lipid droplet in response to adrenergic stimulation. Surprisingly, Mfn2-adKO mice were protected from high-fat diet-induced insulin resistance and hepatic steatosis. Altogether, these results demonstrate that Mfn2 is a mediator of mitochondria to lipid droplet interactions, influencing lipolytic processes and whole-body energy homeostasis.

KEYWORDS:

brown adipose tissue; insulin resistance; lipid droplet; mitochondrial dynamics; mitofusin 2

PMID:
28348166
PMCID:
PMC5452040
DOI:
10.15252/embj.201694914
[Indexed for MEDLINE]
Free PMC Article

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