The discovery of a genetic mutation has given researchers at Boston University School of Medicine, USA, new insights into the cellular mechanisms that link obesity to Type 2 diabetes.
Dr Gerald Denis and his colleagues studied the gene, called Brd2, which had not previously been linked to body energy balance.
AdvertisementWhile complete absence of the gene was fatal, 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.
However, around 20 - 30 percent 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).
"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," Denis said.
"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," he added.
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.
"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," Denis said.
The findings appear in the current issue of The Biochemical Journal.
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