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Fat cells reach their limit and trigger changes linked to type 2 diabetes

8 November 2010

Scientists 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.

Research funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council (MRC) and the European Union Sixth Framework Programme, shows that a protein called secreted frizzled-related protein 1 (SFRP1) is produced by fat cells and may be involved in changes to our metabolism that could increase the risk of diabetes and cardiovascular disease. The work was carried out at the University of Cambridge and will be published in a future edition of the International Journal of Obesity.

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.

Dr 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.

The researchers 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.

Professor Douglas 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."

ENDS

Notes to editors

For further information contact Jaswinder K. Sethi BSc, DPhil, tel: 01223 762633, email: jks30@cam.ac.uk or Antonio Vidal-Puig MD PhD FRCP, tel: 01223 762790, email: ajv22@cam.ac.uk.

Genevieve Maul, University of Cambridge Communications, tel: 01223 765542, email: genevieve.maul@admin.cam.ac.uk.

About University of Cambridge

The University of Cambridge's mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. It admits the very best and brightest students, regardless of background, and offers one of the UK's most generous bursary schemes.

The University of Cambridge's reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history's greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.

About MRC

For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

About BBSRC

BBSRC is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £470M in a wide range of research that makes a significant contribution to the quality of life in the UK and beyond and supports a number of important industrial stakeholders, including the agriculture, food, chemical, healthcare and pharmaceutical sectors.

BBSRC provides institute strategic research grants to the following:

  • The Babraham Institute
  • Institute for Animal Health
  • Institute of Biological, Environmental and Rural Sciences (Aberystwyth University)
  • Institute of Food Research
  • John Innes Centre
  • The Genome Analysis Centre
  • The Roslin Institute (University of Edinburgh)
  • Rothamsted Research

The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.