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Overview
Obesity is associated with a number of comorbidities, including several forms of heart disease. Although obesity is one of the greatest challenges facing 21st century healthcare, effective therapies remain limited. Our research investigates the mechanisms underlying body weight regulation and the pathogenesis of obesity. A major focus of our work is to understand the role that gut hormones play in regulating body weight and glucose homeostasis. We undertake a ‘bench to bedside’ approach from molecular mechanisms to whole animal physiology and assessment of behavior. Our approaches include in vitro cell line studies, quantitative gene expression analysis, neuroanatomical mapping studies, generation of tissue specific knock out mice and studies in healthy volunteers and obese patients. Our ultimate aim is to identify new preventative and therapeutic strategies for obesity. Our research is supported by the Medical Research Council, Wellcome Trust, Rosetrees Trust and UCL/UCLH Comprehensive Biomedical Centre.
Key research activities
- Mechanisms Underlying the Beneficial Metabolic Effects of Bariatric Surgery
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Bariatric (weight-loss) surgery is the most effective method for long-term weight reduction in patients with morbid obesity, reducing co-morbid conditions and mortality. There is increasing evidence that the reduced appetite and improved glucose homeostasis observed in the early post-operative period after certain types of bariatric surgery is due to alterations in circulating gut hormones. In order to gain further understanding of these processes we undertake studies on patients undergoing bariatric surgery at UCLH. In addition, we have established a mouse model of bariatric surgery to enable us to gain further mechanistic insights.
- Neuroimaging
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We are undertaking brain functional magnetic resonance imaging (fMRI) studies coupled with detailed physiological studies in human subjects to investigate how peripheral signals act upon the brain to regulate appetite. Recently, using this approach we have shown that the gut hormone, peptide, acts upon homeostatic and hedonic brain circuits to regulate feeding behaviour.
- Genome Wide Association Studies (GWAS) and Obesity Pathogenesis
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GWAS studies have identified several obesity SNPs however, the mechanisms by which these SNPs mediate their effects on bodyweight is unclear. In order to gain insights into the mechanisms by which GWAS identified obesity SNPs mediate their effects on body weight we have generated a database of normal weight volunteers and patients with raised body mass index in whom we are undertaking detailed phenotyping studies based on genotype.
