Type 2 diabetes linked to limit in expansion of fat cells
12 Nov 2010
Scientists at Cambridge University have found that the fat
cells and tissues of morbidly obese people and animals can reach a limit
in their ability to store fat appropriately.
Beyond this limit several biological processes conspire to prevent
further expansion of fat tissue and in the process may trigger other
health problems such as diabetes.
A protein called secreted frizzled-related protein 1 (SFRP1) is
produced by fat cells and may be involved in changes to human
metabolism that could increase the risk of diabetes and
Research was funded by the UK Biotechnology and Biological Sciences
Research Council (BBSRC), the Medical Research Council (MRC) and the
European Union Sixth Framework Programme. It will be published in a
future edition of the International Journal of Obesity Research.
Professor Antonio Vidal-Puig from the Institute of Metabolic
Science, University of Cambridge said "We have known for some time
that many obese individuals are at greater risk of developing
diabetes, cardiovascular disease and also cancer. But this is not
true for all obese people."
Dr Jaswinder Sethi, also from the
Institute of Metabolic Sciences, University of Cambridge added "What
we still do not fully understand, is how the expansion of fat tissue
is regulated in healthy people and how this process of regulation
might be different in those obese people who have health problems
such as the metabolic syndrome."
One hypothesis is that
storing surplus fat in itself may not lead to metabolic syndrome but
there may be a maximum limit of how much fat a person can store
safely before the body's natural responses lead to the debilitating
chronic health problems often associated with obesity.
Sethi continued "To investigate this we have been using a
combination of molecular cell biology, human gene profiling and
mouse genetics as tools to understand what is happening as fat cells
and tissues develop and then, in some very obese people, lose their
normal process of regulation."
The researchers have found
that the level of SFRP1 increases as fat cells and tissues increase
in volume until it peaks at about the point of mild obesity. There
is evidence that SFRP1 is involved in recruiting new fat cells,
thereby facilitating the expansion of fat tissue up until this point
where it peaks.
"SFRP1 seems to be very closely linked to
some sort of tipping point, after which the way in which our fat
tissue is regulated changes significantly and there are knock-on
consequences to our wider metabolism. We think that in very obese
people this may be an early event that triggers metabolic syndrome
and the chronic health problems associated with it, such as diabetes
and cardiovascular disease," said Dr Sethi.
The fat tissue of
people who are obese and also have diabetes shows signs of not being
regulated as it usually would be. In this tissue, the researchers
also see the levels of SFRP1 begin to fall so as to prevent further
expansion of the tissue. It is this fall in SFRP1 that has knock-on
effects on metabolism that may in part explain the link between
morbid obesity and metabolic syndrome.
believe that SFRP1 works in concert with other molecules to respond
to the availability, or not, of energy. Together these molecules
also determine to what extent our fat tissue can continue to expand
as we consume more calories than we burn.
Kell, BBSRC Chief Executive said: "Research such as this leads to
better understanding of the biochemistry that drives normal human
physiology. In particular we can see how we usually respond to
extremes brought on by the various onslaughts of our lifestyles and
environments. Increasing our understanding of the fundamentals of
metabolic signalling is an important part of working towards an
increase in health span to match our increasing life spans."