Dataset Information


Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis.

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.

PROVIDER: S-EPMC5887905 | BioStudies | 2017-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC5452040 | BioStudies
| S-EPMC7089966 | BioStudies
| S-EPMC7334538 | BioStudies
| S-EPMC7647184 | BioStudies
| S-EPMC7031813 | BioStudies
| S-EPMC8762460 | BioStudies
| S-EPMC8408225 | BioStudies
| S-EPMC7125133 | BioStudies
| S-EPMC8016305 | BioStudies
| S-EPMC4772955 | BioStudies