Lack of stimulation of cholesterol ester transfer protein by cholesterol in the presence of a diet high in monounsaturated fatty acids

Sukhinder Kaur Cheema, Alka Agarwal-Mawal, Cathy M. Murray, and Stephanie Tucker

Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland NL AIB 3X9

Corresponding Author: skaur{at}mun.ca

Cholesterol ester transfer protein (CETP) is a key protein involved in reverse cholesterol transport pathway. The regulation of CETP by dietary fats is not clearly understood. Transgenic mice expressing human CETP under the control of its natural flanking region were fed low or high fat diets enriched in monounsaturated (MUFA) or saturated fatty acids (SFA), in the presence or absence of cholesterol. Addition of cholesterol to the low fat MUFA diet increased CETP activity and mRNA expression, whereas addition of cholesterol to the high fat MUFA diet led to a decrease in CETP activity and mRNA expression. In SW 872 cells oleic acid and cholesterol stimulated CETP gene expression when given alone. However, addition of fatty acids along with cholesterol interfered with the stimulatory effect of cholesterol on CETP gene regulation. Cholesterol mediated stimulation of CETP involves the transcription factor LXRa. High fat MUFA diets inhibited the expression of LXRa and addition of cholesterol to the high fat MUFA diet did not rescue LXRa expression. Evidence is therefore presented for the first time that inhibition of LXRa expression by high fat MUFA diet leads to inhibition of CETP stimulation by cholesterol.

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