High density lipoprotein inhibits the activation of sterol regulatory element-binding protein-1 in cultured cells.
A link between cellular uptake of high density lipoprotein (HDL) and regulation of sterol regulatory element-binding protein-1 (SREBP-1) was investigated in vitro. HDL decreased nuclear SREBP-1 levels as well as SREBP-1 target gene expression in HepG2 and HEK293 cells. However, HDL did not repress an exogenously expressed, constitutively active form of SREBP-1. HDL increased cellular cholesterol levels, and cellular cholesterol depletion by methyl-beta-cyclodextrin abolished the effects of HDL. These results suggest that HDL inhibits the activation of SREBP-1 through a cholesterol-dependent mechanism, which may play an important role in regulating lipid synthetic pathways mediated by SREBP-1.
Yoshida
Masaki
M
Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima-city, Japan. zyousyou8@yahoo.co.jp
Harada
Nagakatsu
N
Yoshida
Keiko
K
Nakagawa
Tadahiko
T
Shimohata
Takaaki
T
Mawatari
Kazuaki
K
Takahashi
Akira
A
Sakaue
Hiroshi
H
Nakaya
Yutaka
Y
D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008297:Male; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects*
D008075:Lipoproteins, HDL; D051780:Sterol Regulatory Element Binding Protein 1; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase