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Monash University Student Information SessionProfessor Bronwyn Kingwell
75 Commercial Road Melbourne
Baker IDI mission
To reduce death and disability from cardiovascular disease, diabetes and other health disorders related to obesity, through
research, clinical care, education and advocacy.
Metabolic and Vascular PhysiologyBronwyn Kingwell
• Integrative, translational, human physiology
• Combine basic bench-top & physiological techniques in humans to investigate major questions relevant to:
type 2 diabetes coronary diseasePeripheral arterial disease
• Understanding pathophysiology with a view to developing novel:
diagnostics therapeutics
VascularCoronary disease
Markers of unstable CAD
Peripheral arterial diseaseOcclusive
Aneurysmal / Marfan
Metabolic & Vascular Physiology
MetabolicHDL Metabolic Anti-inflammatory Platelet
Exercise mimeticsNitric oxide
Brown Adipose Tissue
Epigenetic effects of high fat diet Rabbit Rat Human
Multidisciplinary approach to discovery & translation of novel molecular mechanisms to clinical application
Acute HDL Elevation(reconstituted HDL, CSL-111)
Lowers blood glucose• ↑ skeletal muscle glucose uptake (AMPK)• ↑ insulin secretion
Infusion duration (hrs)0 1 2 3 4
P
las
ma
Glu
co
se
(m
mo
l/L
)
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
rHDLPlacebo
*
Drew et al., Circulation, 2009
Primary Human Skeletal Muscle Cell Culture
Human Abdominal Adipose Biopsies
Pancreas
HDL
insulin
Plasma glucose
?Skeletal muscle
Glucose uptake
Other tissues
CaMKK
AMPK
Ca2+
ABCA1
Glucose uptake
Current Projects
• Chronic HDL elevation– Clinical trials– Human primary skeletal muscle cell culture
• Additional novel pathways– Anti-inflammatory effects and insulin sensitivity– Profiling
VascularCoronary disease
Markers of unstable CAD
Peripheral arterial diseaseOcclusive
Aneurysmal / Marfan
Metabolic & Vascular Physiology
MetabolicHDL
Metabolic Anti-inflammatory Platelet
Exercise mimeticsNitric oxide
Brown Adipose Tissue
Epigenetic effects of high fat diet Rabbit Rat Human
Multidisciplinary approach to discovery & translation of novel molecular mechanisms to clinical application
Brown adipose tissue
• Release/store fat depending on demand• Low energy expenditure• Abundant in humans
• Small quantity• Potentially very high energy expenditure• Not present/active in adult humans??
WAT BAT
BAT: Obesity – Why and How?
• Theoretically 50gm of activated BAT could add 20% additional total basal energy expenditure
50-100g BAT
Current Projects• Activate BAT in obesity• Cell explants/transplants• Induce progenitor cells to form BAT
BAT progenitors
Myogenic progenitors
Novel BAT activating/differentiation factors +/- adipogenic cocktail
Human Muscle
Analysis for BAT characteristics/function
Metabolic and Vascular PhysiologyProfessor Bronwyn Kingwell
www.baker.edu.au
