The Role of Exosomes in Improvement of Insulin Sensitivity in Obese Adolescents following Bariatric Surgery

Background: Exosomes, a type of extracellular vesicle, are a novel mode of tissue-to-tissue communication. Recent work suggests a role of exosomes in the development of obesity-related metabolic disease, such as insulin resistance or type 2 diabetes. With bariatric surgery, individuals undergo significant weight reduction and dramatic metabolic improvements. We hypothesize that exosomes mediate the metabolic improvements following bariatric surgery.

Methods: We performed comprehensive exosome analyses, including measuring size and serum concentration of exosomes, and evaluating exosomal microRNAs expression pattern in 30 teenagers who underwent sleeve gastrectomy (age=16.7± 0.4 years; gender=26 females, 4 males; race= 19 Caucasians, 11 African Americans). Individuals who had ever been diagnosed with diabetes were excluded from the study.

Results: We observed a significant reduction in serum exosome concentration (pre-op= 4.47x10⁸± 6.28X10⁷particles/mL; post-op=2.56x10⁸± 2.44X10⁷particles/mL, p=0.01), and a drastic shift of exosomal RNA expression pattern 1 month after bariatric surgery in obese adolescents, in concurrent with a modest initial weight loss (Pre-op weight=138.6± 5.3kg, Post-op weight=123.3± 5.0kg).

Conclusion: Drastic changes in exosome profile were observed 1 month after bariatric surgery in severely obese adolescents. It is interesting that the most significant change happens in the first month after the surgery with a modest initial weight reduction, indicating the presence of molecular processes responsible for the improvements in metabolic condition following bariatric surgery, independent of weight loss. These findings suggest that the exosomes play a key role in the profound metabolic improvements following bariatric surgery, and serve as a novel biomarker or a therapeutic target for metabolic diseases.