Acyl-ghrelin mediated lipid retention and inflammation within in vitro and ex vivo adipose depots

• Main Author: Churm, Rachel
• Other Authors: Prior, Sarah L. ; Stephens, Jeffrey W. ; Davies, Jeffrey S.
• Published: Swansea University 2018
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752383

The 28 amino acid hormone, ghrelin, has been found to have various effects on metabolism. This thesis focuses on the pathways integrated into ghrelin’s effect within adipocytes and adipose tissue depots of those with and without Type 2 diabetes. To determine whether acyl-ghrelin plays a role in mediating the metabolic state in an in vitro and ex vivo setting this thesis investigates cellular mechanisms via the analysis of: lipid staining, lipid retention gene expression pathway, inflammatory marker levels and determination of oxidative burden. This project confirms and translates previous murine model findings that establishes a mediatory role for acyl-ghrelin within lipid retention. Furthermore, this mechanism is influenced and magnified within the presence of hyperglycaemia, indicating that the impact of glucose metabolism on acyl-ghrelin and lipid homeostasis may result in the deterioration of dyslipidaemia. In addition to novel findings relating to lipid retention, results indicate that acyl-ghrelin also impacts the inflammatory state. Acyl-ghrelin exposure resulted in a marked decrease in pro-inflammatory marker IL-6, and ghrelin mRNA expression was associated with an increase in IL-10 and total antioxidant status. The promotion of the inflammatory state in the presence of acyl-ghrelin may yield novel therapeutic avenues for acyl-ghrelin combination treatment in the amelioration of the low-grade inflammation present within Type 2 diabetes.