Intermittent Fasting Remodels Mitochondrial Morphology and Bioenergetic Capacity in Brown Adipose Tissue of Obese Mice

Brown adipose tissue (BAT) is a specialized adipose tissue that is associated with thermogenesis, endocrine function, and energy expenditure, characterized by a high mitochondrial density. However, obesity induces profound structural and functional remodeling of mitochondria in BAT, compromising their thermogenic and oxidative capacities. On the other hand, intermittent fasting is a non-pharmacological approach that can enhance mitochondrial function, thereby contributing to weight loss. Despite this, the effects of intermittent fasting on the morphofunctional aspects of BAT mitochondria are not yet well understood. Thus, we investigated the effects of a chronic 16:8 daily intermittent fasting protocol over 8 weeks on the BAT mitochondria of obese mice. Diet-induced obesity reduced energy expenditure, increased body weight gain, and adiposity within the BAT. Obesity altered BAT mitochondrial morphology, resulting in smaller, more rounded organelles with disrupted cristae. Conversely, intermittent fasting increased energy expenditure, reduced body weight gain and adiposity within the BAT, increased the UCP1 protein content, and restored browning in the BAT. Remarkably, intermittent fasting promoted extensive remodeling of mitochondrial dynamics protein markers and structural profile in BAT, increasing mitochondrial elongation, total cristae length, and cristae alignment. In addition, intermittent fasting increased the maximum intrinsic capacity of respiratory mitochondrial complexes and the content of proteins related to oxidative phosphorylation. These findings demonstrate that intermittent fasting is a potential strategy for regulating mitochondrial dysfunction in BAT during metabolic disorders.