Project Number: 1935-41000-066-02
Project Type: Nonfunded Cooperative Agreement

Start Date: Apr 01, 2007
End Date: Aug 31, 2009

Objective:
The goal of the research is to reduce the risk of cardiovascular diseases (CVD) and type 2 diabetes by studying the effect of trans fatty acids on the peroxisome proliferator-activated receptors (PPARs) and adipokines in mammalian cells. Epidemiological studies have demonstrated that trans fat intake is associated with a higher risk of cardiovascular disease and type 2 diabetes. The causes of this adverse health effect of dietary trans fat are not well understood, however, and there have been few studies on their mode of action at the molecular or cellular level.

Approach:
Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear transcription factors. They activate the transcription of target gene upon binding with ligand. Adipokines are a group of proteins produced mainly by adipocytes, including the leptin, adiponectin and resistin. The PPARs and adipokines modulate lipid metabolism, glucose homeostasis, and are involved in the development of CVD and diabetes. Fatty acids are the ligand of PPARs and can also affect the secretion of adipokines. The effect of trans fatty acids on plasma lipid profile suggested that trans fat plays a significant role in lipid metabolism. These facts lead us to hypothesize that trans fatty acids may increase the risk of CVD and diabetes through PPARs and adipokines- mediated mechanisms. Trans fatty acids bind the PPARs and cause the change of PPARs activity. In addition, trans fatty acids might affect the secretion of adipokines in adipose tissue. Changes of PPARs activity and adipokines level will eventually affect the lipid metabolism, insulin sensitivity, and vascular biology, leading to the higher risk of CVD and diabetes. To test the hypothesis, we will: 1) Analyze the distribution of trans fatty acids in tissues of hamsters fed with trans fatty acids; 2) investigate the effect of trans fatty acids on the PPARs activity, and 3) Investigate the effect of trans fatty acids on level of adipokines (leptin, adiponectin and resistin) in the plasma of the hamsters. This study will aid in revealing the mechanisms of the effect of trans fatty acids on cardiovascular diseases and type 2 diabetes.