The researchers were studying the gene, called Brd2, which had not previously been linked to body energy balance. While complete absence of the gene was fatal, Dr Denis found that in mice where there had been a single, genetic change in the Brd2 gene, fortuitously reducing its expression, the mice became severely obese – but did not go on to develop Type 2 diabetes.
This result was very surprising because in both 'mice and men', chronic obesity commonly leads to Type 2 diabetes, with its life-threatening consequences, including heart disease, kidney and nerve damage, osteoporosis, blindness and circulation problems in the feet that can require amputation.
If the mice had been human their weight would be equivalent to approximately 270 kilograms (600 pounds); despite this, they exercised at the same levels as normal mice and, in comparison, lived for a surprisingly long time.
Obesity is linked to the development of Type 2 diabetes, and as obesity levels soar – it is predicted that there will be around 366 million diabetic individuals worldwide by 2030 – there is an urgent need for a much deeper biological understanding of the forces that link obesity and diabetes, in order to design new drugs and therapies for treatment.
However around 20 – 30% of the adult obese population remain relatively healthy despite their obesity. These are populations with a healthy metabolism but who are obese (MHO) while others are metabolically obese but are at a normal weight (MONW).
Dr Denis said, "Studies have shown that these individuals have a reduced 'inflammatory profile'. Inflammation caused by normal immune cells called macrophages leads to insulin resistance and Type 2 diabetes - this inflammation is typically seen in connection with obesity but it is the inflammation that is a trigger for diabetes, not the obesity itself. The mechanisms that explain this protection from diabetes are not well understood."
He went on to add, "Much like these protected obese humans, the Brd2-deficient mice have reduced inflammation of fat and never develop failure of the beta cells in the pancreas that is associated with Type 2 diabetes".
The researchers suggest several mechanisms by which the Brd2 gene mutation may protect against the development of diabetes.
These mice have impaired production of inflammation molecules that are normally seen in infections, but that also contribute to Type 2 diabetes. This impairment has the surprising benefit of protecting them from obesity-induced diabetes.
Commenting on the findings, Dr Denis said, "The strong influence of Brd2 levels on insulin production and action suggest that Brd2 is likely to be a promising target for diabetes treatment, but also imply that overactive Brd2 might cause diabetes. The ways in which Brd2 affects the immune system may also play a part in Type 1 diabetes, further studies to determine this are needed."
Further information available from Dianne Stilwell, e- mail firstname.lastname@example.org; tel +44 (0)20 8977 6510; mob +44 (0)7957 200214
Notes for Editors
1. "Brd2 disruption in mice causes severe obesity without Type 2 diabetes" by Fangnian Wang, Hongsheng Liu, Wanda P. Blanton, Anna Belkina, Nathan K. LeBrasseur and Gerald V. Denis, will be published in The Biochemical Journal (2009) Vol 425, part 1, pp 71-83 at www.biochemj.org on 14 December 2009
2. Dr Gerald Denis is at the Cancer Research Center, Boston University School of Medicine, Room K520, 72 East Concord Street, Boston MA 02118, USA. He can be contacted through Gina DiGravio, Media Relations Manager at Boston University School of Medicine Tel + 1 617-638-8480, e-mail email@example.com
3. Pictures to accompany the story are available from Dianne Stilwell or Gina DiGravio – contact details above; Picture caption as follows:
"Despite obesity, mice with the depleted Brd2 gene avoid Type 2 diabetes and several other life-threatening complications normally seen in human obesity. They may provide a model to discover the molecular pathways that could be used to protect obese humans."
4. This research was supported by a grant from the National Institutes of Health, specifically the National Institute of Diabetes, Digestive and Kidney Diseases.
5. The Biochemical Journal is published on behalf of the Biochemical Society by Portland Press Limited. Portland Press Limited is a not-for-profit publisher of journals, books and electronic resources in the cellular and molecular life sciences. It also delivers association management solutions for publishers, learned societies and membership-based organizations.
Gina DiGravio | EurekAlert!
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences