The intake of a high-fat diet and grape seed procyanidins induces gene expression changes in peripheral blood mononuclear cells of hamsters: capturing alterations in lipid and cholesterol metabolisms

Abstract

We previously demonstrated that hamsters that were fed either a standard diet (STD) or a high-fat diet (HFD) and treated with a grape seed procyanidin extract (GSPE) showed decreased adiposity and circulating levels of free fatty acids compared with hamsters treated with a vehicle (Caimari et al. in Int J Obes 37:576-83, 2013, doi:10.1038/ijo.2012). Here, we tested whether the gene expression changes in peripheral blood mononuclear cells (PBMCs) can reflect these metabolic effects and the dyslipidaemia produced by the HFD feeding in the same cohort of animals. The mRNA levels of a subset of genes were also studied in the liver in order to evaluate the capacity of PBMCs to reflect the metabolic adaptations that occur in this organ. In PBMCs, we reported a simultaneous up-regulation of the lipid-related genes involved in both the anabolic (pparc, acc1 and gpat) and the catabolic (ppara, ucp2, atgl and hsl) pathways in response to the GSPE treatment, similar but no identical to previous observations in retroperitoneal white adipose tissues of these animals. Furthermore, the key cholesterol metabolism genes srebp2 and ldlr were significantly down-regulated in PBMCs of both HFD-fed groups compared with the STD groups. Although the expression of srebp2 in the liver followed a similar pattern to that obtained in PBMCs, no comparable changes were found between the liver and PBMCs in the expression of most of the studied genes. In conclusion, our results highlight the potential of PBMCs as a high accessible tissue for the indirect study of cholesterol and adipose tissue metabolism dynamics.

Peripheral Blood Mononuclear Cell Metabolism Acutely Adapted to Postprandial Transition and Mainly Reflected Metabolic Adipose Tissue Adaptations to a High-Fat Diet in Minipigs

“…In contrast, the metabolic profile of PBMC evaluated at the molecular and biochemical levels was particularly close to the one observed in the AT. This is in line with similar conclusions draws in several studies in humans [ 45 ] and laboratory animals [ 16 , 44 ], specially concerning lipid metabolism [ 46 ]. In contrast to this, other metabolic features, like pentose phosphate potential seems to have a PBMC-specific behaviour, with a strong dependence on glucose uptake and phosphorylation and a lower induction capacity when compared to the AT.…”

“…When compared to the results discussed above, the metabolic response observed in the PBMCs in the obese minipig at the fasting state seems to be coherent with the adaptations reported in the major organs involved in the intermediary metabolism. As in a previous study in hamsters [ 44 ] our results show that PBMC metabolism does not reflect that of the liver. In contrast, the metabolic profile of PBMC evaluated at the molecular and biochemical levels was particularly close to the one observed in the AT.…”

Extract Enriched in Flavan-3-ols and Mainly Procyanidin Dimers Improves Metabolic Alterations in a Mouse Model of Obesity-Related Disorders Partially via Estrogen Receptor Alpha

“…In particular, the in vivo hypotriglyceridemic effect of dietary procyanidins involves the activation of the farnesoid X receptor, the subsequent upregulation of the nuclear receptor small heterodimer partner expression and the downregulation of SREBP1 expression ( Del Bas et al, 2009 ). Another study also reports that the reduction of the lipid content in white adipose tissue and the improvement of plasma lipid profile induced by grape seed procyanidin traitement involve the activation of both β-oxidation and the glycerolipid/free fatty acid cycle ( Caimari et al, 2013 ).…”

“…Flavanols (cathechins and procyanidins) have antioxidant/free radical scavenging abilities ( Galleano et al, 2010 ) and anti-inflammatory effects ( Terra et al, 2011 ). They correct lipid abnormalities associated with obesity ( Quesada et al, 2009 ; Caimari et al, 2013 ), prevent insulin resistance ( Al-Awwadi et al, 2005 ; Montagut et al, 2010 ) and exert protective effects against cardiovascular diseases ( Rasmussen et al, 2005 ; Corder et al, 2006 ). Anthocyanins limit weight gain, and improve lipid profiles, hepatic function ( Wu et al, 2013 ) and insulin resistance ( Nizamutdinova et al, 2009 ) associated with obesity.…”

Procyanidins from hawthorn (Crataegus pinnatifida) alleviate lipid metabolism disorder via inhibiting insulin resistance and oxidative stress, normalizing the gut microbiota structure and intestinal barrier, and further suppressing hepatic inflammation and lipid accumulation

“…22 In particular, the study of Castell-Auvi et al 23 found that grape seed procyanidins had a lipid-lowering effect by improving beta-cell functionality. And Caimari et al 24 found the up-regulation of lipid-related genes involved in both the anabolic and catabolic pathways in response to procyanidin treatment. In addition, Rong et al 25 also reported that the litchi pericarp procyanidins could relieve the lipid disorder in Apo E-mice by regulating gene expressions involved in hepatic lipid homeostasis.…”