Gene That Regulates Obesity and Diabetes Identified

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.

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While 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.

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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.

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"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.

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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.

Source-ANI
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