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, Hiroyuki Arai

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)2642-2644
Number of pages3
JournalFASEB Journal
Volume20
Issue number14
DOIs
Publication statusPublished - 2006 Dec
Externally publishedYes

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Biosynthesis
Cholesterol
Liver
Proteins
Fasting
Plasmas
Fibric Acids
PPAR alpha
Pharmaceutical Preparations
Triglycerides
Protein Biosynthesis
Small Intestine
Up-Regulation
Enzymes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis. / Shibata, Norihito; Jishage, Kou Ichi; Arita, Makoto; Watanabe, Miho; Kawase, Yosuke; Nishikawa, Kiyotaka; Natori, Yasuhiro; Inoue, Hiroyasu; Shimano, Hitoshi; Yamada, Nobuhiro; Tsujimoto, Masafumi; Arai, Hiroyuki.

In: FASEB Journal, Vol. 20, No. 14, 12.2006, p. 2642-2644.

Research output: Contribution to journalArticle

Shibata, N, Jishage, KI, Arita, M, Watanabe, M, Kawase, Y, Nishikawa, K, Natori, Y, Inoue, H, Shimano, H, Yamada, N, Tsujimoto, M & Arai, H 2006, 'Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis.', FASEB Journal, vol. 20, no. 14, pp. 2642-2644. https://doi.org/10.1096/fj.06-6368fje
Shibata, Norihito ; Jishage, Kou Ichi ; Arita, Makoto ; Watanabe, Miho ; Kawase, Yosuke ; Nishikawa, Kiyotaka ; Natori, Yasuhiro ; Inoue, Hiroyasu ; Shimano, Hitoshi ; Yamada, Nobuhiro ; Tsujimoto, Masafumi ; Arai, Hiroyuki. / Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis. In: FASEB Journal. 2006 ; Vol. 20, No. 14. pp. 2642-2644.
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