Adipose Tissue Exosome Research and Application

As the largest secretory organ of the organism, adipose tissue can participate in regulating the physiological and pathological processes of proximal and distal tissues/organs by releasing cytokines, hormones, and exosomes. Exosomes as significant messengers of intercellular communication are a hot spot in adipose tissue research. In the past, studies mainly focused on body fluid-derived or cell culture supernatant-derived exosomes, and as the research progresses and the level of research increases, adipose tissue-derived exosomes are receiving more and more attention. Creative Biolabs provides comprehensive services for the isolation, identification, histological profiling, and functional modification of adipose tissue exosomes.

Human adipose tissue is classified according to specific storage areas, structural organization, cell size, and biological function: white adipose tissue (including visceral white adipose tissue, subcutaneous white adipose tissue), brown adipose tissue, and beige adipose tissue. In contrast to visceral adipose tissue, subcutaneous white adipose tissue, and brown adipose tissue are capable of promoting metabolism. Adipose tissue contains adipose-derived mesenchymal stem cells that can differentiate into a variety of cells, and adipose tissue grafts developed on this basis are widely used as candidates for physiological studies and human reconstructive surgery. Adipose exosomes are important members of the exosome family, secreted from adipocytes, and have been shown to play major roles in tissue regeneration, oxidative stress, immune regulation, and many other aspects. Several classic research concepts for adipose tissue exosome applications are highlighted below for reference.

Adipose Tissue Exosomes as Biomarkers

White adipose tissue exosomes have been screened as candidate markers of obesity and its comorbidities. Researchers extracted adipose tissue exosomes from obese and lean populations and analyzed the differences in overall features and protein profiles between the two by characterization and mass spectrometry, finding that half of the proteins were identical in exosomes from visceral tissue and subcutaneous fat, while obese visceral adipose tissue exosomes were enriched for more obesity-related adipokines. Classification of these differential protein data according to biological function showed that obese visceral adipose tissue exosomes exhibited enrichment of proteins associated with adipose tissue inflammation and insulin resistance, such as TGF-β1, CAVN1, CD14, thrombospondin-1, AHNAK, etc. Further SWATH analysis screened candidate exosomal molecular markers of morbid obesity from differential proteins featuring decreased syntenin 1 and elevated TGF-β1 and mimecan, facilitating clinical quantification and diagnosis.

Fig.1 Isolation and TEM images of adipose tissue exosomes. (Camino, 2022)

Adipose Tissue Exosomes Involved in Intercellular Communication

The key to studying the function of adipose tissue exosome-mediated intercellular communication is to verify the presence of shared cell membrane components between the two cell types and the exosomes delivering proteins within them. After several weeks of transplantation of adipose tissue labeled with cell membranes into the host fat pad, detection of fluorescently labeled signals in adipocytes at the transplantation site allows analysis of the exchange of membrane components between adipocytes and other cell types in the tissue. Before the co-cultivation of adipocytes with other cells, knockdown of target genes in recipient cells, detection of target protein signals in recipient cells, as well as setting up an exosome biogenesis inhibitor as a negative control, allows in vitro analysis of intercellular molecular transfer based on exosome mechanisms. The isolated adipose tissue exosomes were then profiled for density, morphology, particle size, vesicle markers, mass spectrometry, and target protein assays to dissect exosome components associated with signal transduction potential.

Adipose Tissue Exosomes Localize Distal Organ Regulation

There is also a strong association between adipose tissue exosome regulation of the distal organs and increased disease risk. Studies have demonstrated that adipose tissue exosomes in a high-fat diet deliver pro-inflammatory miRNAs to the distal gut and exacerbate colitis. Tail vein injections of isolated adipose, muscle, and liver tissue exosomes after labeling were administered to mice. In vivo tracing revealed that adipose tissue-extended exosomes were able to accumulate in the lamina propria of the intestine. This demonstrated the transfer of adipose tissue exosomes between different tissues and organs. Then, injection of adipose tissue exosomes derived from high-fat diet mice to lean mice induced worsening of colitis, and histological profiling revealed that pro-inflammatory miR-155 enriched in exosomes acted as key functional molecules into distal target organs as well as promoted M1-type polarization of macrophages. In light of this finding, engineered modification of high-fat diet adipose tissue exosomes to load miR-155 inhibitor and delivery to high-fat diet mice significantly prevented the dextran sodium sulfate-induced colitis phenotype.

Fig.2 High-fat diet adipose tissue exosomes deliver pro-inflammatory miRNAs to aggravate colitis. (Wei, 2020)

Adipose tissue exosomes are not only capable of intercellular delivery within tissues, but also of circulating and localizing to distal organs to perform their functions. Changes in their cargo composition can reflect the normal or disease state of the body and can be studied as disease markers such as morbid obesity. In addition, similar to other types of exosomes, adipose tissue exosomes are engineered to facilitate the investigation of functional mechanisms and their application as therapeutic vectors. Creative Biolabs provides research services for multi-directional profiling and multi-domain applications of adipose tissue exosomes, helping clients to advance projects related to adipose tissue exosomes. Please contact us to discuss your project.

References

Camino, T.; et al. Human obese white adipose tissue sheds depot-specific extracellular vesicles and reveals candidate biomarkers for monitoring obesity and its comorbidities. Transl Res. 2022, 239: 85-102.
Wei, M.; et al. Visceral adipose tissue derived exosomes exacerbate colitis severity via pro-inflammatory miRNAs in high fat diet fed mice. ACS Nano. 2020, 14(4): 5099-5110.

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