Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-13T03:49:16.619Z Has data issue: false hasContentIssue false
  • English
  • Français

The cholesterolaemic effects of dietary fats in cholesteryl ester transfer protein transgenic mice

Published online by Cambridge University Press:  09 March 2007

Chen-Kang Chang  and
Jean T. Snook
Chen-Kang Chang
Affiliation:
The OSU Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
Jean T. Snook*
Affiliation:
The OSU Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
*
†Corresponding author: Professor J. T. Snook, fax +1 614 292 8880, email snook.3@osu.edu
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

In order to investigate the role of cholesteryl ester transfer protein (CETP) in the cholesterolaemic response to dietary fats, we analysed plasma lipid profiles of CETP-transgenic and control C57BL/6 mice fed standard chow (AIN-93G; AIN), a low-fat diet, and diets high in butter (saturated fatty acids; SFA), high-oleic acid safflower oil (monounsaturated fatty acids; MUFA), and safflower oil (polyunsaturated fatty acids; PUFA) for 5 weeks. Each group contained four or five mice. There were significant diet and diet×genotype effects on plasma total cholesterol (TC; P = 0·035 and P = 0·008 respectively), liver TC (P < 0·001 and P = 0·002 respectively), and esterified cholesterol (EC; P = 0·002 and P = 0·001 respectively); diet effects on plasma triacylglycerol (P = 0·007), liver free cholesterol (P < 0·001), and body weight (P = 0·027); a genotype effect on body-weight gain (P = 0·014); and a diet×genotype effect on energy intake (P = 0·006). In transgenic mice the SFA diet caused significantly higher plasma TC than the PUFA diet (P < 0·05). In control mice MUFA and PUFA diets, but not the SFA diet, caused significantly higher plasma TC than the low-fat and AIN diets (P < 0·05). Transgenic mice fed PUFA had lower plasma TC (P = 0·040), while transgenic mice fed MUFA had lower LDL+VLDL-cholesterol (P = 0·013) than controls in the same dietary groups. Transgenic mice fed MUFA and PUFA diets also had significantly higher liver TC (P = 0·020 and P = 0·002 respectively) and EC (P = 0·040 and P = 0·036 respectively) than controls fed the same diets. In the present study we showed that: (1) CETP transgenic mice had a cholesterolaemic response to dietary fats similar to that in human subjects; (2) CETP transgenic mice fed PUFA showed significantly lower plasma TC, while those fed MUFA had lower LDL+VLDL-cholesterol than controls; (3) hepatic accumulation of cholesterol, possibly resulting from the combination of the enhanced cholesteryl ester transfer to apolipoprotein B-containing lipoproteins and increased hepatic uptake of cholesterol, may contribute to the cholesterol-lowering effect of MUFA and PUFA in CETP-transgenic mice; (4) CETP may play a role in appetite and/or energy regulation.

Keywords

Cholesteryl ester transfer proteinCholesterolTransgenic mice
Type
Short communication
Information
British Journal of Nutrition , Volume 85 , Issue 6 , May 2001 , pp. 643 - 648
Copyright
Copyright © The Nutrition Society 2001

References

Bucci, C, Seru, R, Annella, T, Vitelli, R, Lattero, D, Bifulco, M, Mondola, P & Santillo, M (1998) Free fatty acids modulate LDL receptor activity in BHK-21 cells. Atherosclerosis 137, 329–340.CrossRefGoogle ScholarPubMed
Carlson, SE & Goldfarb, S (1977) A sensitive enzymatic method for determination of free and esterified tissue cholesterol. Clinica Chimica Acta 79, 575–582.CrossRefGoogle ScholarPubMed
Chang, CK, Tso, TK, Snook, JT, Zipf, WB & Lozano, RA (1999) Sandwich enzyme-linked immunosorbent assay for plasma cholesteryl ester transfer protein. Clinical Biochemistry 32, 257–262.CrossRefGoogle ScholarPubMed
Clee, SM, Zhang, H, Bissada, N, Miao, L, Ehrenborg, E, Benlian, P, Shen, GX, Angel, A, LeBoeuf, RC & Hayden, MR (1997) Relationship between lipoprotein lipase and high density lipoprotein cholesterol in mice: modulation by cholesteryl ester transfer protein and dietary status. Journal of Lipid Research 38, 2079–2089.Google Scholar
Gauthier, B, Robb, M, Gaudet, F, Ginsburg, GS & McPherson, R (1999) Characterization of a cholesterol response element (CRE) in the promoter of the cholesteryl ester transfer protein gene: functional role of the transcription factors SREBP-1a, -2, and YY1. Journal of Lipid Research 40, 1284–1293.Google Scholar
Grass, DS, Saini, U, Felkner, RH, Wallace, RE, Lago, WJ, Young, SG & Swanson, ME (1995) Transgenic mice expressing both human apolipoprotein B and human CETP have a lipoprotein cholesterol distribution similar to that of normolipidemic humans. Journal of Lipid Research 36, 1082–1091.CrossRefGoogle ScholarPubMed
Jiang, XC, Agellon, LB, Walsh, A, Breslow, JL & Tall, A (1992) Dietary cholesterol increases transcription of the human cholesteryl ester transfer protein gene in transgenic mice. Dependence on natural flanking sequences. Journal of Clinical Investigation 90, 1290–1295.Google Scholar
Katan, MB, Zock, PL & Mensink, RP (1994) Effects of fats and fatty acids on blood lipids in humans: an overview. American Journal of Clinical Nutrition 60, 1017S–1022S.CrossRefGoogle ScholarPubMed
Kurushima, H, Hayashi, K, Toyota, Y, Kambe, M & Kajiyama, G (1995) Comparison of hypocholesterolemic effects induced by dietary linoleic acid and oleic acid in hamsters. Atherosclerosis 114, 213–221.Google Scholar
LeBoeuf, RC, Puppione, DL, Schumaker, VN & Lusis, AJ (1983) Genetic control of lipid transport in mice. I. Structural properties and polymorphisms of plasma lipoproteins. Journal of Biological Chemistry 258, 5063–5070.CrossRefGoogle ScholarPubMed
Mata, P, Alvarez-Sala, LA, Rubio, MJ, Nuno, J & De Oya, M (1992 a) Effects of long-term monounsaturated- vs polyunsaturated-enriched diets on lipoproteins in healthy men and women. American Journal of Clinical Nutrition 55, 846–850.Google Scholar
Mata, P, Garrido, JA, Ordovas, JM, Blazquez, E, Alvarez-Sala, LA, Rubio, MJ, Alonso, R & de Oya, M (1992 b) Effect of dietary monounsaturated fatty acids on plasma lipoproteins and apolipoproteins in women. American Journal of Clinical Nutrition 56, 77–83.Google Scholar
Peterson, J, Bengtsson-Olivecrona, G & Olivecrona, T (1986) Mouse preheparin plasma contains high levels of hepatic lipase with low affinity for heparin. Biochimica et Biophysica Acta 878, 65–70.CrossRefGoogle ScholarPubMed
Reeves, PG, Nielsen, FH & Fahey, GC (1993 a) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. Journal of Nutrition 123, 1939–1951.CrossRefGoogle Scholar
Reeves, PG, Rossow, KL & Lindlauf, J (1993 b) Development and testing of the AIN-93 purified diets for rodents: results on growth, kidney calcification and bone mineralization in rats and mice. Journal of Nutrition 123, 1923–1931.CrossRefGoogle ScholarPubMed
Snedecor, GW & Cochran, WG (1980) Statistical methods, 7th ed. Ames, IA: The Iowa State University Press.Google Scholar
Sorci-Thomas, M, Prack, MM, Dashti, N, Johnson, F, Rudel, LL & Williams, DL (1989) Differential effects of dietary fat on the tissue-specific expression of the apolipoprotein A-I gene: relationship to plasma concentration of high density lipoproteins. Journal of Lipid Research 30, 1397–1403.CrossRefGoogle ScholarPubMed
Tall, A (1995) Plasma lipid transfer protein. Annual Review of Biochemistry 64, 235–257.CrossRefGoogle Scholar