Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis.
EMBO Rep
; 18(7): 1123-1138, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28539390
ABSTRACT
BAT-controlled thermogenic activity is thought to be required for its capacity to prevent the development of insulin resistance. This hypothesis predicts that mediators of thermogenesis may help prevent diet-induced insulin resistance. We report that the mitochondrial fusion protein Mitofusin 2 (Mfn2) in BAT is essential for cold-stimulated thermogenesis, but promotes insulin resistance in obese mice. Mfn2 deletion in mice through Ucp1-cre (BAT-Mfn2-KO) causes BAT lipohypertrophy and cold intolerance. Surprisingly however, deletion of Mfn2 in mice fed a high fat diet (HFD) results in improved insulin sensitivity and resistance to obesity, while impaired cold-stimulated thermogenesis is maintained. Improvement in insulin sensitivity is associated with a gender-specific remodeling of BAT mitochondrial function. In females, BAT mitochondria increase their efficiency for ATP-synthesizing fat oxidation, whereas in BAT from males, complex I-driven respiration is decreased and glycolytic capacity is increased. Thus, BAT adaptation to obesity is regulated by Mfn2 and with BAT-Mfn2 absent, BAT contribution to prevention of insulin resistance is independent and inversely correlated to whole-body cold-stimulated thermogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo Marrom
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Resistência à Insulina
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Termogênese
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GTP Fosfo-Hidrolases
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article