High basal fractional cholesterol synthesis is associated with nonresponse of plasma LDL cholesterol to plant sterol therapy  

Oleh:

Rideout, Todd C. ; Harding, Scott V. ; Mackay, Dylan

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The American Journal of Clinical Nutrition vol. 92 no. 01 (Jul. 2010), page 41-46.
Topik: CHOLESTEROL SYNTHESIS AND ABSORPTION; LDL CHOLESTEROL

Ketersediaan

Perpustakaan FK Nomor Panggil: A07.K.2010.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Background: The cholesterol-lowering effectiveness of plant sterol (PS) therapy is hindered by wide-ranging variability in LDL-cholesterol responsiveness across individuals. To capitalize on the LDL-cholesterol-lowering potential of PS in the clinical setting, it is paramount to characterize the metabolic factors that underlie this heterogeneity of responsiveness. Objective: The objective was to investigate the relation between cholesterol synthesis and plasma LDL-cholesterol reductions in response to PS consumption. Design: We evaluated previously conducted clinical PS interventions incorporating stable-isotope measures of cholesterol synthesis and conducted feeding studies in animal models of response (Syrian Golden hamsters) and nonresponse (C57BL/6J mice) to PS consumption. Results: From our clinical study population (n = 113), we identified 47 nonresponders (3.73 ± 1.10% change in LDL cholesterol) and 66 responders (–15.16 ± 1.04% change in LDL cholesterol) to PS therapy. The basal cholesterol fractional synthesis rate (FSR) as measured by direct deuterium incorporation was 23% higher (P = 0.003) in the nonresponder subgroup than in responders to PS therapy. The basal cholesterol FSR correlated (r = 0.22, P = 0.02) with the percentage change in LDL cholesterol after PS intervention. In support of our clinical observations, nonresponding mice showed a 77% higher (P = 0.001) basal cholesterol FSR than that of responding hamsters. Compared with control mice, PS-fed mice showed an increase in hepatic nuclear sterol regulatory element binding protein 2 abundance (1.3-fold of control, P = 0.04) and ß-hydroxy-ß-methylglutaryl coenzyme A reductase–mRNA expression (2.4-fold of control, P = 0.00). Conclusion: The results suggest that subjects with high basal cholesterol synthesis are less responsive to PS treatment than are subjects with low basal cholesterol synthesis.

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