Adipose tissue-derived exosomes (AT-EXO) and their cargo can be transferred to the brain in a membrane protein-dependent manner and affect neurons and synapses to regulate cognitive functions. This is one of the proofs that exosomes mediate brain-adipose communication. Creative Biolabs summarizes the research ideas of tissue exosomes involved in brain-adipose communication and is confident to provide our clients with tissue exosome profiling and functional identification services.
Based on the fact that adipose tissue dysfunction has been shown to induce cognitive impairment in type II diabetes, it is necessary to investigate the potential role of AT-EXO in this and its mechanisms. It has been found that AT-EXO can be involved in brain-adipose telecommunication as novel adipokines. First, by tail vein injection and hippocampal localization of AT-EXO from high-fat diet mice and diabetic patients to normal mice, exosome tracer localization revealed enrichment of AT-EXO in hippocampal neurons of mice, with normal mice exhibiting significant synaptic loss and cognitive dysfunction. In contrast, alterations in target organ phenotype were eliminated by removing the effects of the source organ with surgery or by blocking exosome biogenesis with exosome inhibitors, thus confirming in reverse that AT-EXO mediate brain-adipose communication.
Fig.1 Tissue exosomes mediate brain-adipose communication. (Yerrapragada & Bihl, 2022)
Previous studies have also found that adipose tissue produces cytokines that maintain cognitive memory function in the brain, inflammatory factors that induce chronic central inflammatory responses and impair hippocampal dominant cognitive function, and miRNAs that regulate a variety of biological processes. Therefore, histological profiling can screen these cargoes to affect the brain through the process of AT-EXO release. For example, RNA-seq analysis screened for high levels of miR-9-3p as a key differentially expressed molecule in AT-EXO from high-fat mice and diabetic patients compared to normal exosomes. Also, both diabetic and with cognitive impairment, AT-EXO and serum miR-9-3p were significantly upregulated and negatively correlated with cognitive levels. Thus, miR-9-3p may act as miRNAs for adipose exosomes to induce cognitive degeneration in the brain. miR-9-3p delivery by surface AT-EXO targeting brain-derived neurotrophic factors to damage synapses was also confirmed by the results of the subsequent set of suppression miRNAs experiments and transcriptome sequencing. Notably, this also suggests that tissue exosomes do possess a superior barrier-penetrating ability to achieve long-range enrichment to the brain.
Fig.2 AT-EXO impair brain cognitive function. (Wang, 2022)
The isolation and histological analysis of high-purity tissue exosomes facilitate the identification and understanding of their functions and mechanisms in mediating adipose-brain inter-organ communication. Creative Biolabs has established a multi-omics profiling platform for tissue exosomes to facilitate the study of adipose-brain inter-organ communication and support the screening of candidate targets for intervention in adipose-related metabolic diseases and brain-related neurological disorders. Please contact us to learn more.
References