## 3 Secretory Profile of Exosomes in Metabolic Tissues
### Liver  
The liver, the largest internal organ in the human body, plays a crucial role in various physiological processes, including metabolism, detoxification, digestion, synthesis, and storage. In a healthy state, hepatocytes--representing the parenchymal cell population--constitute approximately 80% of the liver's total volume. The remaining cellular components comprise non-parenchymal cells, such as hepatic stellate cells [48; 51].  
Hepatocytes can produce exosomes contributing to cytokine- and chemokine-mediated cell formation and restructuring [52]. It has been observed that the exosomes produced by the liver contain a large amount of sphingosine kinase 2 (SK2) to produce sphingosine-1-phosphate (S1P) and thus induce the mechanisms necessary for the growth of new hepatocytes [52]. Evidence also suggests that damaged liver cells release exosomes with Toll-3 receptors that bind to healthy hepatocytes and induce proinflammatory factors for their repair and fibrosis; likewise, the miRNA content promotes the production of new cytokines and proteins that contribute to tissue repair [41; 49; 53; 54]. In this regard, a recent work published by Zhao Y. highlights that the liver is involved in the regulation of adipogenesis through the secretion of exosomes, particularly in patients with lipid overload; it is proposed that this increased secretion of hepatic exosomes is due to the presence of the enzyme geranyl-geranyl diphosphate synthase (GPPS) [15; 55], during liver damage, such as partial hepatectomy, exosomes released by liver cells can promote liver regenerationas they transport growth factors, such as hepatocyte growth factor (HGF), extracellular matrix (ECM) proteins, and Wnt/beta-catenin [53; 56], which are signals that promote cell proliferation and differentiation.  
Likewise, exosomes derived from human umbilical cord stem cells and mesenchymal cells have been shown to promote AMPK-mediated autophagy of liver cells, leading to reduced gluconeogenesis, increased glycogen storage, and increased hepatic glycolysis and lipolysis [50].  
In adipose cells treated with exosomes from liver cells of mice fed a high-fat and high-sucrose diet, a transcriptional response leads increases in the pro-inflammatory factors II-6, II-1B, and TNF-\(\alpha\) by increasing their mRNA levels, causing pro-inflammatory effects in adipocytes [57]. At the same time, it was demonstrated that these exosomes contain a greater amount of triglycerides, which could alter cell-cell communication [57].  
A study has shown that treatment with brown adipose tissue exosomes (BATs) causes a decrease in fatty liver in a mice population fed a high-fat diet; it also causes an increase in metabolism. This also results in decreased the expression of the pro-inflammatory genes TNF-\(\alpha\) and IL-1B, improved body weight, decreased plasma glucose, and better glucose tolerance. The same study showed that these exosomes accumulate in the liver instead of other tissues, producing their most significant effect in this organ [52; 58].  
Interorgan communication via exosomes is complex and has profound effects on metabolism. As described in the previous section, miR-155 and miR-29a can be secreted from adipocytes and induce insulin resistance signaling in hepatocytes and skeletal muscle [38; 48]; however, hepatocytes can also secrete these miRNAs and can disrupt insulin signaling in peripheral tissues by inhibiting the PI3K/Akt pathway [59; 60].