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 language | English |
|---|---|
| Pages (from-to) | 2642-2644 |
| Number of pages | 3 |
| Journal | FASEB Journal |
| Volume | 20 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - 2006 Dec |
| Externally published | Yes |
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ASJC Scopus subject areas
- Medicine(all)
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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 journal › Article
}
TY - JOUR
T1 - Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis.
AU - Shibata, Norihito
AU - Jishage, Kou Ichi
AU - Arita, Makoto
AU - Watanabe, Miho
AU - Kawase, Yosuke
AU - Nishikawa, Kiyotaka
AU - Natori, Yasuhiro
AU - Inoue, Hiroyasu
AU - Shimano, Hitoshi
AU - Yamada, Nobuhiro
AU - Tsujimoto, Masafumi
AU - Arai, Hiroyuki
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=39049183721&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39049183721&partnerID=8YFLogxK
U2 - 10.1096/fj.06-6368fje
DO - 10.1096/fj.06-6368fje
M3 - Article
C2 - 17077281
AN - SCOPUS:33845639955
VL - 20
SP - 2642
EP - 2644
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 14
ER -