Conjugated linoleic acid upregulates LDL receptor gene expression in HepG2 cells.
Conjugated linoleic acid (CLA) exerts anticarcinogenic and antiatherosclerotic effects in animals. The present study was conducted to examine the effects of CLA on LDL receptor (LDLr) expression in HepG2 cells, and to evaluate whether the sterol response element binding protein 1 (SREBP-1) and acyl CoA:cholesterol acyltransferase (ACAT) were involved in the regulation of LDLr expression by CLA. When HepG2 cells were cultured with serum-free DMEM for 48 h, there was a three- to fivefold (P<0.05) increase in LDLr protein and mRNA levels. Incubation of HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH, 5 mg/L) for 24 h decreased LDLr protein and mRNA by 50-70% (P<0.05) and mature SREBP-1 by 20-40% (P<0.05). CLA, but not linoleic acid, antagonized the depressive effects of 25OH and increased both LDLr protein and mRNA abundance twofold (P<0.05). LDLr protein and mRNA abundance were not different when HepG2 cells were cultured with CLA (0.4 mmol/L) plus 25OH in the presence or absence of an ACAT inhibitor (58-035, 1 mg/L). Furthermore, CLA had no effect on SREBP-1 abundance. These results suggest that CLA upregulates LDLr expression via a mechanism that is independent of ACAT and SREBP-1.
Yu-Poth
Shaomei
S
Graduate Program in Nutrition, The Pennsylvania State University, University Park, PA 16802, USA.
Yin
Dezhong
D
Zhao
Guixiang
G
Kris-Etherton
Penny M
PM
Etherton
Terry D
TD
D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000737:chemistry; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000032:analysis; D005227:Fatty Acids / Q000032:analysis / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000032:analysis / Q000235:genetics*; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D006888:Hydroxycholesterols; D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; D011973:Receptors, LDL; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C007997:25-hydroxycholesterol; D002785:Sterol O-Acyltransferase