Boutant 2017 EMBO J

Boutant M, Kulkarni SS, Joffraud M, Ratajczak J, Valera-Alberni M, Combe R, Zorzano A, Cantó C (2017) Mfn2 is critical for brown adipose tissue thermogenic function. EMBO J 36:1543-58.

» PMID: 28348166 Open Access

Boutant M, Kulkarni SS, Joffraud M, Ratajczak J, Valera-Alberni M, Combe R, Zorzano A, Canto C (2017) EMBO J

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.

© 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license. • Keywords: Brown adipose tissue, Insulin resistance, Lipid droplet, Mitochondrial dynamics, Mitofusin 2 • Bioblast editor: Kandolf G • O2k-Network Lab: ES Barcelona Zorzano A, CH Lausanne Canto C

Labels: MiParea: Respiration, mtDNA;mt-genetics 

Organism: Mouse  Tissue;cell: Fat, Fibroblast  Preparation: Intact cells, Homogenate, Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex V;ATP synthase 

Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2017-07