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Mfn2 is critical for brown adipose tissue thermogenic function
Author(s) -
Boutant Marie,
Kulkarni Sameer S,
Joffraud Magali,
Ratajczak Joanna,
ValeraAlberni Miriam,
Combe Roy,
Zorzano Antonio,
Cantó Carles
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694914
Subject(s) - mfn2 , mfn1 , biology , mitochondrial fusion , mitochondrion , microbiology and biotechnology , brown adipose tissue , mitochondrial fission , adipose tissue , endocrinology , genetics , mitochondrial dna , gene
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‐ad KO ) 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‐ad KO 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.