Abstract
Obesity is associated with chronic multi-system bioenergetic stress that may be improved by increasing the number of healthy mitochondria available across organ systems. However, treatments capable of increasing mitochondrial content are generally limited to endurance exercise training paradigms, which are not always sustainable long-term, let alone feasible for many patients with obesity. Recent studies have shown that local transfer of exogenous mitochondria from healthy donor tissues can improve bioenergetic outcomes and alleviate the effects of tissue injury in recipients with organ specific disease. Thus, the aim of this project was to determine the feasibility of systemic mitochondrial transfer for improving energy balance regulation in the setting of diet-induced obesity. We found that transplantation of mitochondria from lean mice into mice with diet-induced obesity attenuated adiposity gains by increasing energy expenditure and promoting the mobilization and oxidation of lipids. Additionally, mice that received exogenous mitochondria demonstrated improved glucose uptake, greater insulin responsiveness, and complete reversal of hepatic steatosis. These changes were, in part, driven by adaptations occurring in white adipose tissue. Together, these findings are proof-of-principle that mitochondrial transplantation is an effective therapeutic strategy for limiting the deleterious metabolic effects of diet-induced obesity in mice.