Dietary procyanidins lower triglyceride levels signaling through the nuclear receptor small heterodimer partner

Abstract

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.

A trimer plus a dimer-gallate reproduce the bioactivity described for an extract of grape seed procyanidins

“…The main objective of this work was to identify the molecule(s) responsible for the bioactivity of a grape seed procyanidin extract that act in vivo as (a) an antihyperglycemic (Pinent et al, 2004), (b) an antiatherogenic (del Bas et al, 2005Bas et al, , 2008 and (c) an antiinflammatory (Terra et al, 2008) product. To meet this objective, three cell lines in which GSPE has been identified as being highly active, namely adipocytes (Pinent et al, 2005;Pinent, Bladé, Salvadó, Arola, & Ardévol, 2005a, 2005b, hepatocytes (del Bas et al, 2005;Puiggròs et al, 2005), and macrophage cells (Terra et al, 2007) were used.…”

“…Values were corrected per milligram of protein, determined using the Bradford methodology (Bradford, 1976). The medium was collected after 24 h treatment and apolipoprotein B was detected as described in del Bas et al (2008).…”

Effect ofVaccinium ashei readeLeaf Extracts on Lipid Metabolism in Obese OLETF Rats

“…34) Moreover, a grape seed procyanidin extract upregulated CPT under the regulation of the nuclear receptor small heterodimer partner in mouse liver. 35) It is therefore likely that the proanthocyanidins from the BBL hot water extract were also actively involved in lipolysis. A previous study has demonstrated that BBL extracts contained a large amount of oligomeric and polymeric anthocyanidins.…”

Dietary procyanidins enhance transcriptional activity of bile acid‐activated FXR in vitro and reduce triglyceridemia in vivo in a FXR‐dependent manner

“…In HepG2 cells, grape procyanidins require the activity of SHP to reduce secretion of TG whereas, in contrast, they reduce the secretion of ApoB in a SHP-independent way [16]. Also, SHP mediates the hypotriglyceridemic effect of grape procyanidins in wild-type mouse in the postprandial state, which is accompanied by the downregulation of hepatic expression of transcription factor SREBP1 [16], a master mediator for insulin/glucose signaling to lipogenesis (reviewed in [17, 18]).…”