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Dietary procyanidins lower triglyceride levels signaling through the nuclear receptor small heterodimer partner
Author(s) -
Del Bas Josep Maria,
Ricketts Marie Louise,
Baiges Isabel,
Quesada Helena,
Ardevol Anna,
Salvadó Maria Josepa,
Pujadas Gerard,
Blay Mayte,
Arola Lluis,
Bladé Cinta,
Moore David D.,
FernandezLarrea Juan
Publication year - 2008
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200800054
Subject(s) - apolipoprotein b , small heterodimer partner , chemistry , endocrinology , medicine , receptor , mediator , signal transduction , microbiology and biotechnology , nuclear receptor , biochemistry , cholesterol , biology , transcription factor , gene
Hypertriglyceridemia is an independent risk factor in the development of cardiovascular diseases, and we have previously reported that oral administration of a grape seed procyanidin extract (GSPE) drastically decreases plasma levels of triglycerides (TG) and apolipoprotein B (ApoB) in normolipidemic rats, with a concomitant induction in the hepatic expression of the nuclear receptor small heterodimer partner (NR0B2/SHP). Our objective in this study was to elucidate whether SHP is the mediator of the reduction of TG‐rich ApoB‐containing lipoproteins triggered by GSPE. We show that GSPE inhibited TG and ApoB secretion in human hepatocarcinoma HepG2 cells and had and hypotriglyceridemic effect in wild‐type mouse. The TG‐lowering action of GSPE was abolished in HepG2 cells transfected with a SHP‐specific siRNA and in a SHP‐null mouse. Moreover, in mouse liver, GSPE downregulated several lipogenic genes, including steroid response element binding protein 1c (SREBP‐1c), and upregulated carnitine palmitoyltransferase‐1A (CPT‐1A) and apolipoprotein A5 (ApoA5), in a SHP‐dependent manner. In HepG2 cells GSPE also inhibited ApoB secretion, but in a SHP‐independent manner. In conclusion, SHP is a key mediator of the hypotriglyceridemic response triggered by GSPE. This novel signaling pathway of procyanidins through SHP may be relevant to explain the health effects ascribed to the regular consumption of dietary flavonoids.