Scientists Identify Potential New Target for Diabetes, Heart Disease

A new cellular pathway that could help in developing therapeutic treatments for obesity-related disorders, like diabetes and heart disease has been discovered by a team of researchers.

The experts, led by Tapan Chatterjee at the University of Cincinnati, found that action by the enzyme histone deacetylase 9 (HDAC9) could lead to obesity-induced body fat dysfunction and that HDAC9-regulated pathways could be targets for potential treatment options in obesity-related diseases.

"Failure of fat cells to differentiate and properly store excess calories in obesity is associated with adipose tissue (fat) inflammation, fatty liver disease, insulin resistance, diabetes and increased cardiovascular diseases," said Chatterjee.

"We know that dysfunctional fat tissue is the underlying culprit in obesity-related diseases; however, we do not know why fat tissue becomes dysfunctional when a person becomes obese," he added.hatterjee said researchers in this study first identified HDAC9 regulator of fat cell differentiation within the living organism.

"Caloric intake promotes HDAC9 down-regulation to allow the conversion of precursor fat cells to 'functional' fat cells, capable of efficiently storing excess calories for future use and also maintaining whole body lipid and glucose stability," he said.

"Ideally, fat cells should function as a reversible storage site of excess calories and as an endocrine organ to maintain systemic lipid and glucose stability. Unfortunately, during chronic over-feeding, we find HDAC9 level is up-regulated in fat tissue, thereby blocking the conversion which leads to adipose tissue dysfunction and the onset of diseases such as diabetes, liver disease, high blood pressure and heart disease-the nation's No. 1 killer," Chatterjee added.

Researchers examined various members of the HDAC family of proteins and found that only HDAC9 showed a direct correlation to differentiation of precursor fat cells, both from human and mouse fat tissues.

"HDAC9 down-regulation is necessary for the differentiation of precursor fat cells to mature fat cells; forced up-regulation of HDAC9 by genetic manipulation blocks the differentiation of the precursor fat cells," said Chatterjee.

"On the other hand, precursor fat cells from HDAC9 genetic knockout mice showed accelerated differentiation. We believe that HDAC9 keeps precursor fat cells in the undifferentiated state; metabolic cues trigger HDAC9 down-regulation allowing conversion of the precursor cells to mature fat cells," he added.

The researchers are pursuing studies to understand how diet regulates HDAC9 levels in fat tissue and how HDAC9 up-regulation can be prevented during diet-induced obesity through pharmacological means.

"Our findings may help lead researchers to targeted therapies that may prevent the development of obesity-related disorders in humans," Chatterjee said.

The research was presented recently at the American Heart Association's Scientific Session in Chicago.

Source: ANI