Exosome-like vesicles in intercellular communication: Investigating the role of exosomal proteins in the pathophysiology of obesity and exploring the potential therapeutic use of exosomes.

Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by impaired insulin sensitivity, resulting in hyperglycemia, dyslipidemia, and other metabolic changes that can damage organs and tissues over time. Obesity is the primary risk factor for the development of T2DM, as it triggers chronic inflammation in adipose tissue, leading to the secretion of adipokines that reduce insulin sensitivity in peripheral tissues. On their part, exosomes, small extracellular vesicles that cells use for intercellular communication, are critical players in fundamental biological processes such as cell growth, metabolism, and inflammation. Changes in the production or composition of exosomes can lead to health issues. In this dissertation, we explore the role of exosomes in cell-to-cell communication and their potential therapeutic use, focusing on the proteomic alterations that occur in exosomes during obesity and their potential functional consequences. The experimental work in this dissertation is divided into three parts. First, we studied the effect of hyperglycemia on cell function in adipocytic and hepatocytic cell lines. Second, we investigated the changes in exosome proteome resulting from obesity and physical training in a mouse model of diet- induced obesity, emphasizing the functional implications of these alterations. Finally, we evaluated the potential therapeutic use of exosomes to deliver bioactive compounds in vitro. This work aims to enhance our understanding of exosome biology and its relevance to health and disease, particularly metabolic disorders such as obesity and T2DM. By shedding light on the functional consequences of altered exosome proteome and exploring the potential of exosomes for therapeutic purposes, this dissertation provides important insights that may pave the way for novel therapeutic approaches for metabolic disorders.

https://orcid.org/0000-0001-6734-8245