Abnormal metabolism in type 2 diabetes, and how this affects the heart
The study of metabolism has a strong historical basis in Oxford, and in the last 20 years research in this field has undergone a renaissance. Abnormalities in cardiac metabolism have been identified in many pathologies, and have been shown to directly impair the function of the heart, accelerate disease progression and to predict mortality. Given the pivotal role of metabolism in keeping the heart contracting, a greater understanding of what metabolism can do, how this is modified in disease and whether this information can be used to develop new treatments may lead to new therapies for the heart.
Type 2 diabetes is a systemic disease of abnormal metabolism, yet the primary cause of mortality in type 2 diabetes is cardiovascular disease. Important questions remain as to what abnormal cardiac metabolism is doing to the heart in diabetes, and how it is having its effect. We are studying metabolism from 2 angles in diabetes: as a source of energy to power the heart, but also as signalling molecules that can regulate transcription, post-translational modification, and enzyme activity. Our aim is to understand how abnormal metabolism and metabolite levels are exerting their effect on the heart in diabetes. We are particularly interested in the roles played by fats and lipids within the heart, and how these may be driving the metabolic and contractile dysfunction in diabetes. Given the increasing prevalence of diabetes and metabolic syndrome in society, a greater understanding of how diabetes specifically affects the heart, and whether this can be rectified by therapy are important questions.
Our research can be divided into four key questions:
1. How is cardiac metabolism modified in type 2 diabetes?
2. What is this abnormal metabolism doing to the heart – are metabolites acting as signalling molecules?
3. What are the mechanisms regulating changes in cardiac metabolism?
4. Can these mechanisms be targeted by new pharmacological therapies to treat the heart?
Our team
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Lisa Heather
BHF Intermediate Fellow and Associate Professor
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Matthew Kerr
Postgraduate Student
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Claudia Montes Aparicio
Research Assistant
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Rose Matthews
Masters student
Selected publications
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Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes.
Journal article
Dodd MS. et al, (2018), JACC Basic Transl Sci, 3, 485 - 498
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Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation.
Journal article
Mansor LS. et al, (2017), Cardiovasc Res, 113, 737 - 748
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Increased oxidative metabolism following hypoxia in the type 2 diabetic heart, despite normal hypoxia signalling and metabolic adaptation.
Journal article
Mansor LS. et al, (2016), J Physiol, 594, 307 - 320
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Increasing Pyruvate Dehydrogenase Flux as a Treatment for Diabetic Cardiomyopathy: A Combined 13C Hyperpolarized Magnetic Resonance and Echocardiography Study.
Journal article
Le Page LM. et al, (2015), Diabetes, 64, 2735 - 2743
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Differential translocation of the fatty acid transporter, FAT/CD36, and the glucose transporter, GLUT4, coordinates changes in cardiac substrate metabolism during ischemia and reperfusion.
Journal article
Heather LC. et al, (2013), Circ Heart Fail, 6, 1058 - 1066
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The 'Goldilocks zone' of fatty acid metabolism; to ensure that the relationship with cardiac function is just right.
Journal article
Kerr M. et al, (2017), Clin Sci (Lond), 131, 2079 - 2094
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Metabolism, hypoxia and the diabetic heart.
Journal article
Heather LC. and Clarke K., (2011), J Mol Cell Cardiol, 50, 598 - 605
Join the Heather Group
DPhil Students
Do you love metabolism too? We are keen to recruit talented DPhil students to join our group. Please send us an email if you are interested in exploring opportunities with the Heather group.
Postdoctoral Scientists
We welcome applications from talented potential postdoctoral researchers. Vacancies are advertised on the Oxford University and DPAG Vacancies web pages, or we encourage potential applicants to secure fellowship funding.
Our Achievements
DPAG members shine at the Oxford BHF CRE Annual Symposium 2019
17 October 2019
Congratulations are in order to Matthew Kerr, Andia Redpath, Susann Bruche, KC Park and Minahil Mujahid for their achievements at this major showcase for Oxford's British Heart Foundation funded Researchers.
Three DPAG Academics recognised with Teaching Excellence Awards
6 September 2019
The Medical Sciences Teaching Excellence Awards scheme recognises and rewards excellence in teaching, supervision, the organisation and development of teaching, and support for teaching and learning, within a research-intensive environment.
Matthew Kerr to receive the William C Stanley Early Investigator Award
25 April 2019
Congratulations are in order for DPhil student Matthew Kerr, who has been awarded the William C Stanley Early Investigator Award. The award highlights the scientific accomplishments of promising young researchers and is a major focus of the Annual Meeting of the Society for Heart and Vascular Metabolism.
