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Title: The role of Fyn kinase in CRH regulation of energy homeostasis
Author: Ourailidou, Styliani
ISNI:       0000 0004 6348 8904
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2017
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Corticotropin-releasing hormone (CRH) is the master regulator of stress responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis in mammals. CRH and CRH-related ligands, termed urocortins (UCNs), along with their receptors, CRHR1 and CRHR2, are expressed both centrally and peripherally. Evidence has implicated the CRH family of peptides in mechanisms regulating energy balance in the animal. Interestingly, Fyn kinase, a member of the Src kinase family, is also involved in homeostasis regulation. Fyn knockout animals display reduced adiposity partly due to increased energy expenditure and lipid utilization in white adipose tissues. Fyn kinase expression is down-regulated by glucocorticoids, suggesting that HPA axis might regulate Fyn, thereby implying a possible interaction with CRH. I sought to determine a possible crosstalk between CRH and Fyn kinase. Using a mouse model with total Crh deficiency (Crh KO mouse) and applying various metabolic challenges, such as cold exposure and induction of lipolysis processes, Fyn kinase expression was studied in tissues harvested from age-matched WT and Crh KO mice. I uncovered a novel positive correlation between CRH and Fyn kinase that was unmasked upon normalization of the Crh KO blood glucocorticoid. Activation of lipolysis pathways did not affect Fyn kinase expression, but unraveled differences between the two genotypes, both in vivo and in vitro. CRH plays an important role in activating thermogenesis of brown adipose tissue and therefore I sought to determine whether Fyn kinase had similar actions. A novel role for Fyn kinase activity in controlling brown adipogenesis was reported with the use of the brown preadipocyte line, T37i. Additionally, treatment of brown adipocytes with the Fyn kinase activity inhibitor, SU6656, provided evidence of an interaction between Fyn and Akt, whereas ERK1/2 remained unaffected.
Supervisor: Not available Sponsor: University of Warwick
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology