Metabolic and Vascular Physiology

Bronwyn Kingwell

Professor Bronwyn Kingwell
Head, Metabolic and Vascular Physiology
Laboratory
NHMRC Senior Principal Research Fellow
bronwyn.kingwell@bakeridi.edu.au

Assessing haemodynamic and metabolic function in humans

Research Overview

The Metabolic and Vascular Physiology Laboratory addresses important clinical questions across the obesity, diabetes and cardiovascular disease continuum. This work is directed to novel preventive, diagnostic and therapeutic strategies through multidisciplinary approaches combining basic bench-top research with human physiology and investigator-led randomised controlled clinical trials (RCTs). Our work impacts on patient care and has been published in highly regarded journals.

The laboratory is well known for work on vascular biomechanical properties, as well as pioneering studies in exercise research that have elucidated the mechanisms underpinning the cardiometabolic protective effects of physical activity and influenced public health guidelines. Current research directions include identification of novel molecular mechanisms which can be applied in clinical practice, with a particular focus on activation of brown adipose tissue to combat obesity, HDL raising therapies for diabetes, novel treatment strategies for peripheral artery disease and predictors of acute coronary syndromes.

Research projects

Obesity and diabetes mellitus

Brown adipose tissue (BAT): We recently demonstrated for the first time that a single, high oral dose of ephedrine can activate BAT in the majority of young lean males (Diabetologia 2013, upfront feature article). We further established that this activation — as is also the case for cold exposure — is defective in obese adults. In demonstrating pharmacological BAT activation and the disparity between lean and obese adults, this paper represents an important conceptual advance in the search for therapeutics to manipulate BAT. Current work is directed to determining whether it is possible to activate BAT in obese humans and the therapeutic potential of this approach to underpin novel anti-obesity strategies.

HDL therapies: Our group has elucidated a suite of novel actions of HDL with clinical relevance to the HDL raising therapies currently in late phase RCTs for coronary heart disease. The most novel of these relates to the actions of HDL on glucose metabolism and the potential for HDL-raising strategies to prevent and control type 2 diabetes. Current studies are focused on further understanding of the effects of HDL on glycaemic control and include both proof-of-concept clinical trials as well as cell culture approaches. Metabolic and related anti-ischemic actions of HDL in cardiac muscle are also a current interest.

- Vastus lateralis muscle biopsy procedure
Vastus lateralis muscle biopsy procedure for investigation of human muscle cell signaling pathways

Coronary artery disease (CAD)

Worldwide, more than 19 million people experience a sudden cardiac event annually; however, accurate identification of patients at risk for unstable coronary syndromes is still not possible. The Metabolic and Vascular Physiology Laboratory has contributed to the understanding of the biomechanical and genetic contributors to plaque instability. Recent work with our Baker IDI collaborator Associate Professor Peter Meikle using electrospray ionisation mass spectrometry has identified novel lipids contributing to a profile of lipid biomarkers which classify stable and unstable CAD patients more accurately than do traditional risk factors (patent: PCT/AU2010/001596; Arterioscl Thromb Vasc Biol 2011). Current studies aim to refine this model and to elucidate the mechanisms linking plaque stability to the plasma lipidome.

Coronary artery disease patient

A validated risk score incorporating both lipidomic and conventional risk factors could be applied routinely in primary care to identify individuals at risk of acute coronary syndromes

Bronwyn Kingwell

Lab Head profile

Professor Bronwyn Kingwell
BSc(Hons), PhD (University of Melbourne, 1991)

Professor Bronwyn Kingwell is a NHMRC Senior Principal Research Fellow. At the Baker IDI Heart and Diabetes Institute she is Executive Director, Science Policy; Program Leader for Human Physiology and Behavioural Science; and also leads the Healthy Lifestyle Research Centre. She has professorial appointments in the Department of Medicine and Department of Physiology at Monash University; James Cook University; University of Pierre and Marie Curie in Paris; and is a Principal Research Fellow at the University of Melbourne.

Professor Kingwell's work addresses important clinical questions across the obesity-diabetes-cardiovascular disease continuum via a multidisciplinary linkage approach between fundamental research and clinical application. Her contributions have influenced international physical activity guidelines.

Currently, Professor Kingwell is a chief investigator on grants totaling over $18 million including an NHMRC Program Grant, two Clinical Research Excellence (CRE) grants and a Development Grant as well as National Heart Foundation (NHF) and industry grants.

Professor Kingwell has been appointed to leadership roles on the NHMRC and through these roles has contributed to national research policy and practice, and continues to do so as current chair of the National Committee for Medicine of the Australian Academy of Science. She has also had a long association with the NHF in community heart health advocacy with a special interest in healthy lifestyle.

Achievements

Significant prizes / Awards

  • 2011 Endeavour Executive Award - Department of Education, Employment and Workplace Relations
  • 2011 Franco-Australian Exchange Program Award, High BP Research Council
  • 2011 Mairie de Paris Award
  • 2004 RT Hall Career Achievement Prize, CSANZ

Scientific leadership

  • 2009–13 Chair, National Committee for Medicine of the Australian Academy of Science
  • 2009–13 National Heart Foundation Research Committee
  • 2003–09 NHMRC Research Committee
  • 2001–03 NHMRC Council
  • 2005 President, Australian Society for Medical Research (ASMR)

Publication highlights

Carey AL, Formosa MF, Van Every B, Bertovic D, Eikelis N, Lambert GW, Kalff V, Duffy SJ, Cherk MH, Kingwell BA. Ephedrine activates brown adipose tissue in lean but not obese humans. Diabetologia 2013;56(1):147–55.

Drew BG, Rye KA, Duffy SJ, Barter P, Kingwell BA. The emerging role of HDL in glucose metabolism. Nat Rev Endocrinol 2012;8(4):237–45.

Meikle PJ, Wong G, Tsorotes D, Barlow CK, Weir JM, Christopher MJ, MacIntosh GL, Goudey B, Stern L, Kowolczyk A, Haviv I, White AJ, Dart AM, Duffy SJ, Jennings GL, Kingwell BA. Plasma lipidomic analysis of stable and unstable coronary artery disease. Arterioscl Thromb Vascul Biol 2011;31:2723–32.

Patel S, Drew BG, Nakhla S, Duffy SJ, Murphy AJ, Barter PJ, Rye K-A, Chin-Dusting J, Hoang A, Sviridov D, Celermajer DS, Kingwell BA. Reconstituted HDL increases plasma HDL anti-inflammatory properties and cholesterol efflux capacity in patients with type 2 diabetes. J Am Coll Cardiol 2009;53(11):962–71.

Drew BG, Duffy SJ, Formosa MF, Natoli AK, Henstridge DC, Penfold SA, Thomas WG, Mukhamedova N, de Courten B, Forbes JM, Yap FY, Kaye DM, van Hall G, Febbraio MA, Kemp BE, Sviridov D, Steinberg GR, Kingwell BA. HDL modulates glucose metabolism in patients with type 2 diabetes mellitus. Circulation 2009;119(15):2103–11.

Calkin AC, Drew BG, Ono A, Duffy SJ, Gordon MV, Schoenwaelder SM, Sviridov D, Cooper ME, Kingwell BA, Jackson SP. Reconstituted high-density lipoprotein attenuates platelet function in individuals with type 2 diabetes mellitus by promoting cholesterol efflux. Circulation 2009;120(21):2095–U60.

Drew BG, Fidge NH, Gallon-Beaumier G, Kemp BE, Kingwell BA. High density lipoprotein and apolipoprotein AI increase eNOS activity by protein association and multisite phosphorylation. Proc Natl Acad Sci USA 2004;101(18):6999–7004.

Medley TL, Kingwell BA (author for correspondence), Gatzka CD, Pillay P, Cole TJ. MMP-3 genotype contributes to age-related aortic stiffening through modulation of gene and protein expression. Circ Res 2003;92(11):1254–612.

Kingwell BA, Formosa M, Muhlmann M, Bradley SJ, McConell GK. Nitric oxide synthase inhibition reduces glucose uptake during exercise in individuals with type 2 diabetes more than in control subjects. Diabetes 2002;51(8):2572–80.

Kingwell BA, Waddell TK, Medley TL, Cameron JD, Dart AM. Large artery stiffness predicts ischemic threshold in patients with coronary artery disease. J Am Coll Cardiol 2002;40(4):773–39.

Medley TL, Cole TJ, Gatzka CD, Wang YS, Dart AM, Kingwell BA. Fibrillin-1 genotype is associated with aortic stiffness and disease severity in patients with coronary artery disease. Circulation 2002;105(7):810–815.

Ferrier KE, Muhlmann MH, Baguet J-P, Cameron JD, Jennings GL, Dart AM, Kingwell BA. Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension. J Am Coll Cardiol 2002;39(6):1020–1025.

Dart AM, Kingwell BA. Pulse pressure: a review of mechanisms and clinical relevance. J Am Coll Cardiol 2001;37(4):975–984.

Kingwell BA. Nitric oxide mediated metabolic regulation during exercise: Effects of training in health and cardiovascular disease. FASEB J 2000;14(12):1685–1696.

Staff

Postdoctoral Fellows
Dr Andrew Carey
Dr Adèle Richart
Dr Julian Sacre

Honorary Postdoctoral Fellows
Dr Andrew Siebel

Research Assistants
Melissa Formosa
Medini Reddy-luthmoodoo

PhD Students
Rebecca Loh
Pia Varsamis