Virginia Commonwealth University School of Medicine researchers have identified that the removal of cholesterol by a key enzyme called CEH can attenuate inflammation and subsequently affect the development of diabetes, paving the way for new target therapies that may one day prevent diabetes and help predict a patient's susceptibility to the disease.
In the study led by Shobha Ghosh, Ph.D., professor of internal medicine, pulmonary division in the VCU School of Medicine, the team used a transgenic mouse model to examine the role of a key enzyme called CEH, which regulates the removal of cholesterol from cells and makes it available to HDL, or "good cholesterol." By increasing this process, CEH enhances the removal of cholesterol from the body.
Specifically, the team observed that in CEH transgenic mice there is reduced inflammation of the fat tissue. They tested whether this decrease in inflammation due to expression of human CEH gene leads to a decrease in inflammation-linked diseases such as diabetes.
According to Ghosh, the results show that when the CEH transgene is expressed, the mice had improved insulin sensitivity, which suggests a decreased development of Western diet-induced diabetes. This improvement was noted despite equal weight gain in these mice.
"Although diabetes and heart disease often co-exist, current management of diabetes does not necessarily include cholesterol and/or inflammation control," explained Ghosh.
"These studies provide the first evidence that targeting fat tissue inflammation as well as elimination of cholesterol from the body may be emerging new strategies to prevent diabetes," she said.
In previous work, Ghosh's team showed that when the gene for this enzyme was introduced in mice, it significantly reduced Western diet-induced heart disease in the transgenic model.
The work was supported by grants from the National Heart, Lung and Blood Institute and the American Diabetes Association.
The study was published in the April 2010 issue of the Journal of Biological Chemistry.
Ghosh's team included Jinghua Bie, Ph.D., Bin Zhao, Ph.D., and Jingmei Song, M.S., from the VCU Department of Internal Medicine.
- J. Bie, B. Zhao, J. Song, S. Ghosh. Improved Insulin Sensitivity in High Fat- and High Cholesterol-fed Ldlr-/- Mice with Macrophage-specific Transgenic Expression of Cholesteryl Ester Hydrolase: Role of Macrophage Inflammation and Infiltration into Adipose Tissue. Journal of Biological Chemistry, 2010; 285 (18): 13630 DOI: 10.1074/jbc.M109.069781
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