ESPE Abstracts

Introduction: Obesity and related metabolic diseases occur as a chronic imbalance between energy intake and energy expenditure. Due to its high metabolic activity, brown adipose tissue (BAT) has become a promising target for the development of new treatment concepts for metabolic disease. Having a high concentration of mitochondria, BAT is necessary to control the entire energy metabolism of the body. BAT consumes significant amounts of glucose and fatty acids as fuel for energy expenditure by thermogenesis mediated by mitochondrial dissociation protein 1 (UCP1). Exosomes are nanovesicles that share the characteristics of donor cells involved in intercellular communication. BAT-derived exosomes (BAT-Exos) may orchestrate metabolic communication.

Methods: We analyzed the effect of BAT-Exos on cellular metabolism, lipid accumulation, oxidative stress, inflamatory factors in skeletal muscle, adipocytes and liver cell lines. in vitro effects of exosomes were evaluated by cell metabolism analysis. Protein contents of BAT-Exos were analyzed by mass spectrometry.

Results: The results showed that myofibers, hepatocytes, and adipocytes were exposed to BAT-Exos, they showed increased UCP1 protein abundance and cellular metabolism with increased oxygen consumption and proton leakage. These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content. Protein profiling of exosomes demonstrated that BAT-Exos were rich in mitochondria components and involved in catalytic processes. Cells in metabolic communication also increased expression of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial biogenesis, along with a number of BAT selective and beige gene markers.

Conclusion: BAT Exos are important players in mediating cell-to-cell communication as well as interorgan crosstalk between adipose tissue and other distant organs, thereby participating in the regulation of local immune responses, tissue remodeling, systemic insulin sensitivity and energy homeostasis. A more detailed understanding of BAT-Exos as molecular and functional will help increase our metabolic knowledge and facilitate the development of new therapeutics for obesity regulation and the treatment of related metabolic complications.