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Dr. Susan Ozanne
British
Heart Foundation,
University of
Cambridge
Cambridge,
UK
Epigenetics: Neonatal Environment and Nutrition
Tuesday, September 14, 2010
11:00 - 11:30 am
Abstract:
Programming is used
to describe the
process whereby a
stimulus or insult
applied at a
critical period of
development results
in long-term effects
on the structure or
function of an
organism. Over the
last 20 years
immense interest in
programming has been
prompted by results
of epidemiological
studies showing a
relationship between
low birth weight and
type 2 diabetes and
the metabolic
syndrome. Compelling
evidence suggests
that early
environmental
factors such as
early nutrition play
an important role in
mediating these
relationships.
Studies of
individuals exposed
in utero to a
period of famine
have shown a direct
relationship between
maternal nutrition
and glucose
tolerance in the
adult offspring.
Further support for
the importance of
the fetal
environment has come
from studies of
monozygotic twins
who were discordant
for type 2 diabetes.
These revealed that
the diabetic twins
had significantly
lower birth weights
than their
non-diabetic
co-twins. Animal
models have been
developed to
investigate the
mechanisms linking
the early
environment to
future disease
susceptibility. The
most extensively
studied is the
maternal low protein
model where rats are
fed a low (8 %)
protein diet during
pregnancy and
lactation. Offspring
have a low birth
weight and undergo
an age-dependent
loss of glucose
tolerance. This is
associated with
pancreatic ß cell
dysfunction and
insulin resistance.
The latter is
associated with
changes in
expression of key
insulin-signalling
proteins in muscle
and adipocytes.
Similar changes are
observed in muscle
and adipose tissue
from low birth
weight young men.
These differences
occur prior to the
development of
insulin resistance
and type 2 diabetes,
thus may be
molecular markers of
early growth
restriction and
disease risk. The
molecular mechanisms
by which a
phenomenon that
occurs
in utero
has phenotypic
consequences years
later are only just
starting to emerge
and are thought to
involve epigenetic
modifications.
Biography
Dr Susan Ozanne is a British Heart Senior Fellow in the Institute of Metabolic Science Metabolic Research Laboratories and a Fellow of Churchill College, both at the University of Cambridge, U.K. She obtained a first class honours degree in Biochemistry from the University of Edinburgh, Scotland and then her PhD at the University of Cambridge in 1994. Before being appointed to her current post was she a Diabetes U.K. R.D. Lawrence Fellow, a Wellcome Trust Career Development Fellow and a British Heart Foundation Lecturer. Her research interests are focused on understanding the mechanistic basis of the relationship between poor early growth and subsequent risk of disease. Initially her work was directed towards understanding how low birth weight increased risk of type 2 diabetes, however her programme of work has now expanded to include the link between maternal diet, obesity and premature death. Her research group works on animal models of intrauterine growth restriction as well as on biopsy material from low birth weight humans. Dr Ozanne is the author of over 90 peer-reviewed full papers on the early origins of adult disease and is a member of the council of the Society for the Developmental Origins of Health and Disease.
