In vitro and in vivo models investigating pharmacological modulators of the metabolic syndrome

Agarwal, Neera 2010. In vitro and in vivo models investigating pharmacological modulators of the metabolic syndrome. PhD Thesis, Cardiff University.

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Abstract

BACKGROUND: Owing to the long-term health risks associated with increased adiposity and the limited efficacy of existing anti-obesity agents, there is an urgent need for further development of alternative therapeutic options to serve as an adjunct to lifestyle measures to address global cardiometabolic risk and thus reduce the risk of developing obesity-related illnesses such as type II diabetes and cardiovascular disease. AIMS/METHODS: The studies presented in this thesis aimed to investigate the effects of novel (CBi antagonist) and existing (metformin) pharmacological agents on components of the metabolic syndrome using in vitro and in vivo models. This was undertaken with in vitro studies of the effect of CBi receptor modulation on white, brown and primary (subcutaneous and omental) pre-adipocyte proliferation, adipogenesis and adipokine production as well as a randomised, double-blind cross-over trial of the effects of metformin on vascular function and metabolic profile in young women with polycystic ovary syndrome (in vivo). RESULTS: CBi receptor antagonism inhibited white and primary pre-adipocyte proliferation and increased expression of terminal markers of adipogenesis while promoting adiponectin production. In young women with PCOS, short term metformin therapy improved arterial stiffness and endothelial function, resulted in modest weight loss and an elevation in serum adiponectin. There is increasing evidence for the key role the latter plays in metabolic processes and vascular health, and these increases in adiponectin levels may underlie some of the mechanisms mediating the changes observed. Therefore treatments targeting a switch inthe adipokine profile as the therapeutic goal represent a new approach to addressing global cardiometabolic risk.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
ISBN:	9781303195815
Funders:	Royal College of Physicians, Welsh Assembly Government
Date of First Compliant Deposit:	30 March 2016
Last Modified:	09 Jan 2018 17:36
URI:	https://orca.cardiff.ac.uk/id/eprint/54393

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