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Oct 2017 Our autumn newsletter is out now. Find it on our Newsletters page, or subscribe to have it sent to you by email.

 

Oct 2017 In our recent article published in the Journal of Clinical Endocrinology and Metabolism, we used metabolomics to characterise the response to acute caloric restriction in unprecedented detail.

 

 

Physiology

 

A critical part of our research involves undertaking physiological studies in cohorts of patients with genetic forms of obesity to examine the role of the relevant molecules in eating behaviour, energy expenditure and neuroendocrine function. These studies involve measurements of heart rate, gas exchange to assess metabolic rate, body composition, body fat distribution and core temperature. These studies have taught us a great deal about the role of the relevant pathways in physiology, which in turn helps us to investigate, advise and follow up patients in a more informed way.

 

 
By studying patients with leptin and leptin receptor mutations, we have shown that leptin is a key regulator of appetite and modulates the reward value of food. Leptin is also important for the onset of puberty and immune function.

 
Patients with MC4R mutations are hyperphagic, tall with increased lean mass. MC4R deficiency is associated with a lower prevalence of hypertension due to impaired sympathetic tone, thus linking central melanocortin signalling to the regulation of blood pressure.

 
These integrated genetic-molecular-physiological studies have allowed us to demonstrate the pivotal role of the leptin-melanocortin pathway in the regulation of weight. Our ability to study large cohorts of patients in whom the basis for their obesity has been defined at a genetic and molecular level means that we are well positioned to exploit new therapeutic possibilities and we are currently working with several Pharmaceutical companies to contribute to the process of drug development and validation.

 

We are also undertaking a comprehensive longitudinal study of patients with genetic forms of obesity, so we can identify the timing and nature of clinical problems and follow the response to surgical, medical and related interventions. By examining genetic, environmental and lifestyle events, we aim to identify the factors that predict and modulate the clinical course of these disorders. This information is important when trying to establish the case for bringing in new treatments.