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Submitted on July 8, 2004
Accepted on January 4, 2005
Center for Human Nutrition and the Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, in the University of Colorado Health Sciences Center, Denver, CO; Departments of Biochemistry, Surgeryand Internal Medicinein the Brody School of Medicine, East Carolina University, Greenville, NC
* To whom correspondence should be addressed. E-mail: Paul.maclean{at}uchsc.edu.
Cholesteryl ester transfer protein (CETP) is a plasma enzyme that can modulate the profile of lipoproteins and is thus considered a: 1) mediator of vascular disease; and 2) therapeutic target for vascular disease. In the present study we pursued a better understanding of the effect of type 2 diabetes on the expression of CETP in obese patients. Obesity was accompanied by a 20% elevation in plasma CETP that was eliminated with the development of diabetes. These differences were observed for both men and women and were due to variations in the amount of CETP protein in the plasma. The mRNA and protein of both the full length (CETPFL) and alternatively spliced (CETP
9) forms of CETP were lower in the liver, but not in either sc or omental adipose tissue depots, of diabetic obese subjects. Sterol response element binding proteins 1 and 2 were also lower in liver homogenates, suggesting that these transcription factors may mediate the effects of type 2 diabetes on hepatic CETP expression. Thus, the suppressive effects of type 2 diabetes in obese subjects is observed in both men and women and may be due, at least in part, to a suppression of hepatic CETP expression.
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