Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet

Department of Biochemistry and Biotechnology, Unitat d'Enologia del Centre de Referència en Tecnologia dels Aliments de la Generalitat de Catalunya, Universitat Rovira i Virgili, Tarragona, Spain.
The Journal of Nutritional Biochemistry (Impact Factor: 3.79). 08/2008; 20(3):210-8. DOI: 10.1016/j.jnutbio.2008.02.005
Source: PubMed


The main objective of this study was to evaluate the effect of procyanidin intake on the level of inflammatory mediators in rats fed a hyperlipidic diet, which are a model of low-grade inflammation as they show an altered cytokine production.
Male Zucker Fa/fa rats were randomly grouped to receive a low-fat (LF) diet, a high-fat (HF) diet or a high-fat diet supplemented with procyanidins from grape seed (HFPE) (3.45 mg/kg feed) for 19 weeks and were then euthanized. We determined biochemical parameters, C-reactive protein (CRP) and IL-6 levels in plasma. Adipose tissue depots and body weight were also determined. We assessed CRP, IL-6, TNF-alpha and adiponectin gene expression in liver and white adipose tissue (WAT).
As expected, rats fed the HF diet show an enhanced production of CRP. Our results demonstrate that the HFPE diet decreases rat plasma CRP levels but not IL-6 levels. The decrease in plasma CRP in HFPE rats is related to a down-regulation of CRP mRNA expression in the liver and mesenteric WAT. We have also shown a decrease in the expression of the proinflammatory cytokines TNF-alpha and IL-6 in the mesenteric WAT. In contrast, adiponectin mRNA is increased in this tissue due to the procyanidin treatment. As previously reported, CRP plasma levels correlate positively with its expression in the mesenteric WAT, suggesting that procyanidin extract (PE) modulates CRP at the synthesis level. CRP plasma levels also correlate positively with body weight. As expected, body weight is associated with the adiposity index. Also, TNF-alpha expression and IL-6 expression have a strong positive correlation. In contrast, the expression of the anti-inflammatory cytokine adiponectin correlates negatively with the expression of TNF-alpha and IL-6 in the mesenteric WAT.
These results suggest a beneficial effect of PE on low-grade inflammatory diseases, which may be associated with the inhibition of the proinflammatory molecules CRP, IL-6 and TNF-alpha and the enhanced production of the anti-inflammatory cytokine adiponectin. These findings provide a strong impetus to explore the effects of dietary polyphenols in reducing obesity-related adipokine dysregulation to manage cardiovascular and metabolic risk factors.

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Available from: Maria-Josepa Salvadó, May 04, 2014
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    • "Thus, to overcome the detrimental effects of heat stress using new plant derived additives as a natural antioxidant in poultry diets is being researched. Grape (Vitis Vinifera) seeds are considered as a good source of polyphenolic compounds which have been shown to have various beneficial pharmacological effects, including anti-hyper lipidemic (Moreno et al., 2003), anti-inflammatory (Terra et al., 2009), and anti-bacterial activities (Mayer et al., 2008). Shi et al. (2003) reported that the antioxidant potential of grape seed is twenty and fifty fold greater than vitamins E and C, respectively, arising from increased levels of polyphenols proanthocyanidins and oligomers of flavan-3-ol units, especially catechin and epicatechin. "
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    • "Determination of serum IL-6 and adiponectin The serum IL-6 and adiponectin concentrations were measured using ELISA kits supplied by Invitrogen, according to the manufacturer's instructions [26]. The optical density was read at 450 nm on a Varioskan Flash plate reader (Thermofisher Scientific, Nepean, ON, Canada). "
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    • "We also hypothesized that the addition of proanthocyanidins , which constitute the most abundant polyphenols in the human diet, could further improve postprandial metabolic flexibility because these substances are potent antioxidants [20] with hypolipidemic effects [21]. Likewise, proanthocyanidins are anti-inflammatory [22], cardioprotective [20], and decrease risk factors associated with cardiovascular diseases (CVD), such as insulin resistance [23]. Animal studies have demonstrated that proanthocyanidins reduce the plasma levels of atherogenic apolipoprotein B (ApoB) rich in TG and low density lipoprotein (LDL)-cholesterol while simultaneously increasing the levels of antiatherogenic high density lipoprotein (HDL)-cholesterol; the reduction of plasma TGs constitutes their strongest effect [21]. "
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