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Mfn2 is critical for brown adipose tissue thermogenic function.
Journal article

Mfn2 is critical for brown adipose tissue thermogenic function.

  • Boutant M Nestlé Institute of Health Sciences, Lausanne, Switzerland.
  • Kulkarni SS Nestlé Institute of Health Sciences, Lausanne, Switzerland.
  • Joffraud M Nestlé Institute of Health Sciences, Lausanne, Switzerland.
  • Ratajczak J Nestlé Institute of Health Sciences, Lausanne, Switzerland.
  • Valera-Alberni M Nestlé Institute of Health Sciences, Lausanne, Switzerland.
  • Combe R Center of PhenoGenomics (CPG), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Zorzano A Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Cantó C Nestlé Institute of Health Sciences, Lausanne, Switzerland carlos.cantoalvarez@rd.nestle.com.
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  • 2017-03-29
Published in:
  • The EMBO journal. - 2017
brown adipose tissue
insulin resistance
lipid droplet
mitochondrial dynamics
mitofusin 2
Adipose Tissue, Brown
Animals
GTP Phosphohydrolases
Mice
Mice, Knockout
Mitochondria
Perilipin-1
Protein Binding
Thermogenesis
English 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.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/231083
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