Novel effects of prohibitin 1 expression level on cholesterol and lipid homeostasis.

Publisher: Elsevier Science Country of Publication: United States NLM ID: 9010081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4847 (Electronic) Linking ISSN: 09552863 NLM ISO Abbreviation: J Nutr Biochem Subsets: MEDLINE

Publication: <1996->: New York, NY : Elsevier Science
Original Publication: Stoneham, MA, USA : Butterworths, c1990-

Prohibitins* ; Repressor Proteins*/genetics ; Repressor Proteins*/metabolism; Animals ; Humans ; Mice ; Cholesterol/metabolism ; Homeostasis ; Lipid Metabolism ; Lipids ; RNA, Messenger/genetics ; RNA, Messenger/metabolism

Prohibitin 1 (PHB1) plays an important role in maintaining liver health and function. The PHB1 level is decreased in patients with various liver diseases. In this study, liver cancer was induced in liver-specific Phb1 knock-out mice, which were then subjected to hepatic gene and metabolomic analysis. The reduced expression of mRNA expression level of Phb1 induced down-regulation of cholesterol and lipid metabolism. This result was confirmed in a cell model. The expression of Hmgcr and Srebp2 in normal cells decreased when they were treated with cholesterol. In HepG2 cells in which the expression of Phb1 was lowered using siPhb1, the mRNA expression of Hmgcr and Srebp2 also decreased when the cells were treated with cholesterol. Furthermore, in the Phb1 knock-out group, the expression of Fasn and Srebp1 related to lipid metabolism increased but the expression of Ldlr decreased. The expression of Cat and Gpx in cells increased when the expression of Phb1 decreased. Altogether, a decreased expression of Phb1 induces down-regulation of cholesterol- and lipid metabolism-related genes and cholesterol homeostasis is not achieved, particularly in a cholesterol-rich environment. The decrease in Phb1 expression causes excessive oxidative stress in cholesterol and lipid metabolism. Therefore, maintaining a normal level of PHB1 expression is crucial for maintaining cholesterol homeostasis in the liver. Thus, PHB1 may become an important target for non-alcoholic fatty liver disease and lipid metabolism in the future.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

97C5T2UQ7J (Cholesterol)
0 (Lipids)
0 (Prohibitins)
0 (Repressor Proteins)
0 (RNA, Messenger)
0 (prohibitin 1, mouse)

Date Created: 20240104 Date Completed: 20240214 Latest Revision: 20240628

20240628

10.1016/j.jnutbio.2023.109561

38176624