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Title: MicroRNAs in brown and white adipocytes
Author: Dimitri, Federica
ISNI:       0000 0004 7223 966X
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2017
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The adipose tissue has an important role in maintaining the energy homeostasis balance. Understanding its physiology is important for the development of treatments against diseases where this equilibrium is compromised, such as obesity and associated metabolic disorders. MicroRNAs (miRNAs) are important gene regulators and an increasing body of evidence suggests their involvement in adipogenesis and adipose metabolism. MiRNAs can also be secreted into the extracellular environment and be taken up by distal cells, mediating cell-to-cell communication. However, very little is known about adipose tissue-derived circulating miRNAs. Through miRNA PCR array analysis we identified several miRNAs that are differentially secreted among mouse undifferentiated and differentiated brown and white adipocytes, among which, miR-196a and miR-378a-3p showed a conservative pattern of secretion in different adipocyte models. MiR-138-5p was identified as the unique miRNA differentially secreted between human brown and white adipocytes. Bioinformatics target prediction revealed that these miRNAs are potentially involved in important processes regulating the functioning of adipose tissue and its cross-talk with distal cells. By ultracentrifugation of adipose conditioned media and Nanosight technology, we investigated vesicle and vesicle-free miRNA carriers and characterized adipose derived vesicles. Finally, through microRNA array and mRNA sequencing we identified genes, miRNAs and pathways differentially enriched in human brown and white adipocytes contributing to improve the knowledge on the nature of human adipocytes, hampered by the scarce availability of human brown adipose samples. Through integration of the two analyses, we identify poorly known or novel miRNAs, potentially involved in the pathways associated with the genes differentially expressed between human brown and white adipocytes. Among the significantly downregulated miRNAs in brown versus white adipocytes we highlighted miR-513a-3p, miR-4511 and miR-4328. While, among the significantly upregulated miRNAs in brown versus white we highlighted miR-4698, miR-4516, miR-4531, miR-29a-3p and miR-3915.
Supervisor: Not available Sponsor: University of Warwick
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology