Misregulation of Dlk1, a paternally expressed imprinted gene, is known to cause adipose phenotypes in both mice and humans. It is now known that the type of fat a person has, the location of and type of expansion are all important factors for the epidemic of obesity-related diseases, yet there is little understanding of the factors that influence which depots expand, and how. This project investigates how Dlk1, expressed primarily during embryogenesis, effects adulthood adiposity, which has shed light on the mechanism by which embryonic insults affect adulthood adipose physiology and resultant metabolic disease. Much previous work has been done on the role of Dlk1 in adipogenesis in vitro, however little is known of its role in this process in vivo. To achieve an in vivo investigation of its role in adipogenesis, adipose tissue has been measured in mice with deleted Dlk1 from embryo through early life and into adulthood. Gross measurement has been supported by mechanistic interrogation of adipose expandability using a triple transgenic adipocyte labelling mouse model, results from which are the most comprehensive to date in a wild type context and reveal insight into the Dlk1 knock-out phenotype. Results indicate a complex and dynamic role of Dlk1 that is interlinked with overall growth in mice. Moreover new evidence is presented here for tissue specific c imprinting of Dlk1 in some adipose cell types with consequential growth and adipose alterations in Dlk1 heterozygote mice that do not follow the expected phenotype of imprinted gene knock-out models.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:766232 |
| Date | January 2018 |
| Creators | Cassidy, Fearon |
| Publisher | Queen Mary, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://qmro.qmul.ac.uk/xmlui/handle/123456789/46028 |
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