Sulforaphane suppresses the activity of sterol regulatory element-binding proteins (SREBPs) by promoting SREBP precursor degradation
Journal
Scientific reports
Journal Volume
12
Journal Issue
1
Date Issued
2022-05-24
Author(s)
Miyata, Shingo
Kodaka, Manami
Kikuchi, Akito
Matsunaga, Yuki
Shoji, Kenta
Iwase, Masamori
Takeda, Keita
Katsuta, Ryo
Ishigami, Ken
Matsumoto, Yu
Suzuki, Tsukasa
Yamamoto, Yuji
Sato, Ryuichiro
Inoue, Jun
Abstract
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate various genes involved in cholesterol and fatty acid synthesis. In this study, we describe that naturally occurring isothiocyanate sulforaphane (SFaN) impairs fatty acid synthase promoter activity and reduces SREBP target gene (e.g., fatty acid synthase and acetyl-CoA carboxylase 1) expression in human hepatoma Huh-7 cells. SFaN reduced SREBP proteins by promoting the degradation of the SREBP precursor. Amino acids 595-784 of SREBP-1a were essential for SFaN-mediated SREBP-1a degradation. We also found that such SREBP-1 degradation occurs independently of the SREBP cleavage-activating protein and the Keap1-Nrf2 pathway. This study identifies SFaN as an SREBP inhibitor and provides evidence that SFaN could have major potential as a pharmaceutical preparation against hepatic steatosis and obesity.
Subjects
DIET-INDUCED OBESITY; METABOLIC SYNDROME; LIPID-METABOLISM; SMALL-MOLECULE; CELLS; ACTIVATION; INSULIN; INHIBITION; PATHWAY; IDENTIFICATION
SDGs
Publisher
NATURE PORTFOLIO
Type
journal article