Serotonin inhibition to maximise brown adipose tissue activity

  • Research type

    Research Study

  • Full title

    Inhibition of peripheral serotonin synthesis as a novel treatment for obesity and associated metabolic disease

  • IRAS ID

    298012

  • Contact name

    T'ng Choong Kwok

  • Contact email

    choong.kwok@ed.ac.uk

  • Sponsor organisation

    University of Edinburgh

  • Duration of Study in the UK

    1 years, 4 months, 30 days

  • Research summary

    Summary of Research
    Brown fat is a special type of fat which functions to burn calories to keep our bodies warm when we're placed in a cold environment. People who are obese have less brown fat than lean individuals. We have recently discovered that high levels of serotonin stops brown fat from burning energy in humans. 16 healthy humans (8 lean and 8 obese) will be recruited to a study to test if we can make brown fat burn more calories by lowering their serotonin levels through a drug, called telotristat ethyl. This drug reduces the amount of serotonin produced in the body but doesn’t change the serotonin levels in the brain, where it is important to keep our appetite under control and our mood stable. Volunteers will be given telotristat ethyl or placebo in random order for 2 weeks prior to undergoing a positron emission tomography (PET) scan during mild cold exposure to determine the effect on brown fat activity. Volunteers will then cross over to the other phase of the study after a 2-week washout period.

    Summary of Results
    There are 2 main types of fat in the body – brown and white. White fat stores extra energy mainly around our tummy and hips but brown fat is typically found within our neck, near the spine and around the kidneys and has a completely different function. Brown fat burns energy to keep us warm in the cold and therefore its ability to burn energy raises the potential of it being targetted for weight loss treatment. We recently discovered that serotonin (which is a hormone that regulates your appetite in the brain) can reduce human brown fat activity. However, it is unclear if serotonin levels are altered in obesity, or if brown fat can be activated by lowering serotonin levels in the body. To determine whether lowering serotonin levels in the body improves brown fat function, we gave healthy normal weight and obese volunteers a medication (called telotristat ethyl) to reduce the amount of serotonin the body produces. These volunteers were also given a dummy placebo tablet in random order, and we measured their brown fat function during both phases. The telotristat ethyl tablets reduced brown fat activity and increased their cholesterol and blood pressure, suggesting that this medication may in fact increase your risk of getting heart disease, although the reasons why are unclear and requires further research.

  • REC name

    East of Scotland Research Ethics Service REC 2

  • REC reference

    21/ES/0062

  • Date of REC Opinion

    6 Jul 2021

  • REC opinion

    Further Information Favourable Opinion