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Enzyme action could be target for diabetes, heart disease treatments
Date:11/16/2010

us 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," Chatterjee says. "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. We are exploring the cellular signaling mechanism that promotes such down-regulation of this enzyme during the normal fat cell differentiation process."

Chatterjee says researchers were really interested in the tie between increased HDAC9 levels in fat tissue of mice and the caloric overload.

"Fat tissues from these obese mice showed dysfunction, with increased expression of pro-inflammatory agents and decreased expression of hormones responsible for maintaining whole body lipid and glucose stability," he says. "The fat tissues of these mice are not capable of efficiently storing excess calories and are not able to perform proper endocrine functions.

"The adaptive response fails for some reason during chronic caloric overload, leading to the generation of fat tissue mass that is dysfunctional."

Chatterjee says the HDAC9 level in fat cells is the underlying molecular culprit for dysfunctional fat tissue during obesity.

"We are currently examining HDAC9 knockout mice subjected to chronic high-fat feeding and think that HDAC9 gene removal will protect mice from obesity-linked adipose tissue dysfunction and associated metabolic disorders," he says.

"Identification of HDAC9 as a novel regulator of f
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Contact: Katie Pence
katie.pence@uc.edu
513-558-4561
University of Cincinnati Academic Health Center
Source:Eurekalert

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