HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) All Versions of this Article: fj.06-6368fjev1 20/14/2642    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shibata, N. Articles by Arai, H. Search for Related Content PubMed PubMed Citation Articles by Shibata, N. Articles by Arai, H.

Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis

Norihito Shibata^*,, Kou-ichi Jishage, Makoto Arita^*, Miho Watanabe, Yosuke Kawase, Kiyotaka Nishikawa, Yasuhiro Natori, Hiroyasu Inoue^||, Hitoshi Shimano^¶, Nobuhiro Yamada^¶, Masafumi Tsujimoto and Hiroyuki Arai^*,1

^* Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan;

Laboratory of Cellular Biochemistry, Riken, Saitama, Japan;

Pharmacology and Pathology Research Center, Chugai Research Institute For Medical Science, Inc., Shizuoka, Japan;

Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, Tokyo, Japan;

^|| Department of Food Science and Nutrition, Faculty of Human Life and Environment, Nara Women’s University, Nara, Japan; and

^¶ Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

¹Correspondence: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7–3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: harai{at}mol.f.u-tokyo.ac.jp

ABSTRACT

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 (PPAR-)-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- 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.—Shibata, N., Jishage, K.-i., Arita, M., Watanabe, M., Kawase, Y., Nishikawa, K., Natori, Y., Inoue, H., Shimano, H., Yamada, N., Tsujimoto, M., Arai, H. Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis

This article has been cited by other articles:

				M. E. Wright, U. Peters, M. J. Gunter, S. C. Moore, K. A. Lawson, M. Yeager, S. J. Weinstein, K. Snyder, J. Virtamo, and D. Albanes Association of Variants in Two Vitamin E Transport Genes with Circulating Vitamin E Concentrations and Prostate Cancer Risk Cancer Res., February 15, 2009; 69(4): 1429 - 1438. [Abstract] [Full Text] [PDF]