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Title: Regulation of endoplasmic reticulum stress in adipose tissue metabolism
Author: Voyias, Philip D.
ISNI:       0000 0004 5371 1893
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2015
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Obesity is the most significant risk factor for developing type II diabetes mellitus (T2DM). Obesity induces adipocyte endoplasmic reticulum (ER) stress, prior to onset of insulin resistance. A pathological inability of white adipose tissue (WAT) to expand to accommodate excess energy is predominantly due to impaired adipogenesis. The research hypothesis was that ER stress in human WAT is important in inducing WAT dysfunction and subsequent insulin resistance and T2DM. The aims of this study were to elucidate interactions of ER stress in human WAT and to characterise the role of ER stress in human adipogenesis. Abdominal SAT biopsies and anthropometry were collected from T2DM subjects before and after bariatric surgery and non-diabetic subjects. Preadipocytes were extracted from human WAT and differentiated into adipocytes. Lipogenesis, lipolysis, glucose uptake, insulin sensitivity, and ER stress and adipogenesis gene and protein expression were assessed in control cells and with ER stress inducers, inhibitors or siRNA. The results of this study found both restrictive and malabsorptive bariatric interventions are effective weight loss interventions for obese T2DM patients and result in significantly improved glucose and insulin levels six months after surgery. WAT health is better following restrictive procedures as shown by lower and better regulation of ER stress markers. Adipogenesis in primary human preadipocytes is influenced by adiposity and WAT depot and the IRE1-XBP1s UPR is essential in human adipogenesis. XBP1s plays a vital role upstream of CEBP and PPAR in human adipogenesis and it is necessary for mediating the action of insulin. Wnt10b plays an inhibitory role in human adipogenesis and acts independently of XBP1s. Collectively these findings suggest that WAT function is key for metabolic health and can be impaired by ER stress; however regulated adipogenesis may serve to improve WAT function and therefore improve metabolic health.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC Internal medicine