Obesity and health

: Insight from characterizing the metabolomic signatures of weight-loss interventions

Abstract

Obesity is a disease with incompletely understood pathogenesis and complications. In
this thesis, clinical trials of obesity interventions and a cohort study with metabolomics data are used to examine the biology underpinning variation in weight and its consequences for health. Chapter 1 summarises key background information about body weight regulation, obesity pathogenesis, treatments for obesity and metabolomics. Chapter 2 provides methodological details about the data sources and pre-analytical data processing and filtering. In Chapter 3, I present a pilot analysis of a subsample of participants from By-Band-Sleeve (BBS), a clinical trial comparing the effectiveness of gastric bypass, gastric band and sleeve gastrectomy. In conducting this pilot analysis, I established an analytical pipeline for this type of dataset which was then applied to a larger sample of BBS participants in Chapter 4. Here I demonstrate the widespread metabolomic effects of bariatric surgery, finding evidence of changes in a total of 526 metabolites. In Chapter 5 I identify metabolomic changes that differ between the three surgery types, finding evidence for heterogenous change of 19 metabolites, which was not solely due to differences in weight change across the three surgery subtypes. Chapter 6 presents analysis of metabolomics data within a clinical trial of a caloric restriction intervention and compares the results to those from BBS, finding evidence of 75 consistent metabolomic changes across bariatric surgery and caloric restriction. This
potential signature of weight loss is explored further in Chapter 7 where the BBS
metabolomics data is combined with data from a cohort study and exploratory principal component analysis is conducted. Chapter 8 brings together the overarching themes of the thesis, its strengths, limitations, and potential implications. Overall, the thesis characterises the metabolomic signatures of two obesity interventions and explores how these signatures could provide insight into the relationship between obesity and health.

Date of Award	10 Dec 2024
Original language	English
Awarding Institution	University of Bristol
Supervisor	Nicholas John Timpson (Supervisor) & Laura J Corbin (Supervisor)