Metabolic insights into PPAR alpha

  • Research type

    Research Study

  • Full title

    Investigation of phenotypes asssociated with genetic variants of metabolic interest; Metabolic insights into PPAR alpha

  • IRAS ID

    217181

  • Contact name

    Stephen O'Rahilly

  • Contact email

    so104@medschl.cam.ac.uk

  • Sponsor organisation

    Cambridge University Hospitals NHS Foundation Trust and University of Cambridge

  • Duration of Study in the UK

    2 years, 0 months, 0 days

  • Research summary

    Obesity and its associated complications of diabetes, dyslipdaemia, hypertension and fatty liver remains a leading cause of population health. Efforts to reduce the soaring prevalence have been largely unsuccessful and current therapeutic strategies focus on managing the overt complications of obesity. PPAR alpha is a receptor that regulated lipid (fat) metabolism in cells. It is a target of the fibrate class of drugs which have been shown to regulate cholesterol levels in humans. There has also been some benefit observed from using fibrate drugs in fatty liver disease, however this has been in animals. PPAR alpha appears to be an important regulator of lipid metabolism however our understanding of the precise role of PPAR alpha in humans remains unclear as much of the existing evidence is from in vitro and animal studies. The purpose of this study is to advance our knowledge on the influence of PPAR alpha on human lipid metabolism beyond what is known from animal and in vitro models. To do this we will identify individuals who carry variation in the PPAR alpha gene and undertake physiological testing in order to determine a detailed metabolic phenotype. The study cohort will be recruited from the existing population based Fenland study where participants have consented to having their samples retained for future analysis and to be recalled on the basis of the genotype(genetic signature). Phenotyping studies will include assessment of body composition, biochemical assessment, tissue distribution of fat, fat tolerance and fat synthesis. It will be undertaken at the Wellcome Trust Clinical Research Facility, Cambridge Biomedical Campus. Characterising the metabolic phenotype of people with PPAR alpha mutations would provide novel insights into the biological role of PPAR alpha in humans. New findings supported by in vitro and in vivo studies may ultimately identify novel therapeutic targets of metabolic disease.

  • REC name

    South West - Cornwall & Plymouth Research Ethics Committee

  • REC reference

    17/SW/0075

  • Date of REC Opinion

    20 Mar 2017

  • REC opinion

    Favourable Opinion