Monash University Student Information Session Professor Bronwyn Kingwell.

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

[email protected]

www.baker.edu.au