Brown Adipose Tissue Activation Study

  • Research type

    Research Study

  • Full title

    The Effect of Brown Adipose Tissue on Obesity: A study of Cowden Syndrome

  • IRAS ID

    174206

  • Contact name

    Fredrik Karpe

  • Contact email

    fredrik.karpe@ocdem.ox.ac.uk

  • Sponsor organisation

    Clinical Trials and Research Governance

  • Duration of Study in the UK

    4 years, 10 months, 1 days

  • Research summary

    The prevalence of obesity is increasing, causing morbidity, mortality and a large burden on healthcare systems worldwide. It is an imperative to not only better understand obesity but to investigate possible mechanisms for treatment.
    Cowden syndrome is an genetic condition resulting in; increased risk of malignancy, obesity and protection against type 2 diabetes. The cause of obesity in Cowden syndrome is unknown however it has been postulated that it is due to the inability to produce brown adipose tissue.
    Brown Adipose tissue was recently identified as being present in adult humans. It is a subtype of adipose tissue that uses fat and sugar to produce heat, this allows an increase in energy expenditure. It can be activated by cold temperature. Weight maintenance is a function of energy consumption as well as energy expenditure, altered BAT activity could play an important role in disrupting the energy balance and lead to weight gain.

    It is difficult to separate brown adipose tissue by standard imaging modalities as white adipose tissue is macroscopically similar to brown adipose tissue. However, the two types of adipose tissue display different metabolic activity in response to cold. It has been well demonstrated that BAT can be reliably identified through the use of radiolabelled glucose and PET scanning. However, as Cowden patients are more prone to malignancy this is not an appealing option. Recently the technique of chemical exchange saturation transfer MRI (CEST MRI) has been developed which theoretically can detect the metabolic difference between BAT and WAT without radiation. However the BAT must be active to be able to differentiate it from WAT.

    The symptoms of Cowden Syndrome are due to a mutation affecting the PTEN gene. The PTEN gene has been implicated as being involved with the formation of brown fat. If we are able to demonstrate that Cowden patients have a decreased BAT it would be highly suggestive of this as a cause of obesity in Cowden syndrome. Obesity in Cowden syndrome has not previously been explained.
    In addition, given the need for therapies to combat obesity understanding the role of BAT is important and the identification of a cohort of patients with absent BAT could help the study and development of pharmacological methods of augmenting BAT activity.

  • REC name

    South Central - Oxford B Research Ethics Committee

  • REC reference

    15/SC/0510

  • Date of REC Opinion

    21 Oct 2015

  • REC opinion

    Further Information Favourable Opinion