Cholesterol Research Today is a free monthly online journal that collates and summarizes the latest research about Cholesterol, including details on high cholesterol, hdl, ldl, diet, risks. | ||||||||
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Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis.Shibata N, Jishage K, Arita M, Watanabe M, Kawase Y, Nishikawa K, Natori Y, Inoue H, Shimano H, Yamada N, Tsujimoto M, Arai H Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Supernatant protein factor (SPF) is a novel cholesterol biosynthesis-accelerating protein expressed in liver and small intestine. Here, we report on the physiological role of SPF by using Spf-deficient mice. Although plasma cholesterol levels were similar in chow-fed Spf-/- and wild-type (WT) mice, fasting significantly decreased plasma cholesterol levels in Spf-/- mice but not in WT mice. While fasting reduced hepatic cholesterol synthesis rate in WT mice, a more pronounced reduction was observed in Spf-/- mice. The expression of cholesterogenic enzymes was dramatically suppressed by fasting both in WT and Spf-/- mice. In contrast, hepatic SPF expression of WT mice was up-regulated by fasting in peroxisome proliferator-activated receptor alpha (PPAR-alpha)-dependent manner. These results indicate that in WT mice, the decrease of hepatic cholesterol synthesis under fasting conditions is at least in part compensated by SPF up-regulation. Fibrates, which function as a PPAR-alpha agonist and are widely used as hypotriglycemic drugs, reduced hepatic cholesterol synthesis and plasma cholesterol levels by approximately one-half in Spf-/- mice but not in WT mice. These findings suggest that co-administration of fibrates and an SPF inhibitor may reduce not only plasma triglyceride but also cholesterol levels, indicating that SPF is a promising hypocholesterolemic drug target. Published 4 December 2006 in FASEB J, 20(14): 2642-4.
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