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Title: Epigenetic control of the post-bariatric phenotype : the role of microRNAs
Author: Alkandari, Abdullah
ISNI:       0000 0004 6495 5631
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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The rising obesity pandemic and the concomitant rise in its co-morbidities are leading causes of global morbidity and mortality. Bariatric surgery is a form of gastrointestinal surgery that leads to sustained weight loss, diabetes resolution, reduction in cancer risk and other improvements in health. MicroRNAs are a family of small, endogenous, non-coding RNAs that regulate gene expression at the post-transcriptional level. MicroRNAs control expression of over half the human transcriptome and are involved in processes fundamental to both normal physiology and disease, including obesity and diabetes. This study hypothesizes that microRNAs are biomarkers for health improvements following bariatric surgery. Using quantitative PCR, a microRNA baseline was established in the serum and urine of an obese human population and increases in three anti-fibrotic microRNAs were found in urine following bariatric surgery. Circulating microRNA profiles were characterised in Roux-en-Y gastric bypass patients preoperatively and at 5 timepoints postoperatively. Roux-en-Y gastric bypass significantly altered circulating microRNA profiles in a time dependent manner. Relative to preoperative levels, of the 159 circulating microRNAs assayed 2 were significantly deregulated 1 month postoperatively, 5 were deregulated at 3 months, 10 at 6 months, 28 at 9 months and 31 at 12 months. Target prediction and pathway analysis revealed that these differentiated microRNAs regulate biological pathways that are involved in obesity and that microRNAs may contribute to the development of the beneficial post-bariatric phenotype. Both circulating and urinary post-bariatric microRNA levels correlated with measured clinical biomarkers such as BMI and blood glucose. These results indicate that bariatric operations fundamentally alter microRNA expression both in urine and in circulation and suggest that microRNAs represent not only potentially novel biomarkers for improvements in health following surgery, but are possible biological effectors that contribute to the mechanisms behind bariatric surgery. MicroRNA expression profiles could potentially be used to monitor operative outcomes and understanding the role of these differentially expressed microRNAs could shed light behind the mechanism by which bariatric surgery improves health.
Supervisor: Gooderham, Nigel ; Ashrafian, Hutan Sponsor: Government of Kuwait
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral