The Role of Dlk1 in in vivo Adipogenesis
Abstract
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.
Authors
Cassidy, FearonCollections
- Theses [4190]