Mfn2 is critical for brown adipose tissue thermogenic function |
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Authors: | Magali Joffraud Joanna Ratajczak Miriam Valera‐Alberni Roy Combe Antonio Zorzano Carles Cantó |
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Institution: | 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 |
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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. |
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Keywords: | brown adipose tissue insulin resistance lipid droplet mitochondrial dynamics mitofusin 2 |
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