title: Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Ximena
authors.initials: X
authors.lastname: Terra
authors.forename: Gemma
authors.initials: G
authors.lastname: Montagut
authors.forename: Mario
authors.initials: M
authors.lastname: Bustos
authors.forename: Niurka
authors.initials: N
authors.lastname: Llopiz
authors.forename: Anna
authors.initials: A
authors.lastname: Ardèvol
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
authors.forename: Juan
authors.initials: J
authors.lastname: Fernández-Larrea
authors.forename: Gerard
authors.initials: G
authors.lastname: Pujadas
authors.forename: Josepa
authors.initials: J
authors.lastname: Salvadó
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
authors.forename: Mayte
authors.initials: M
authors.lastname: Blay
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects*; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D044945:Proanthocyanidins / Q000627:therapeutic use*; D051381:Rats; D011924:Rats, Zucker; D027843:Vitis / Q000737:chemistry
chemical_list: D052242:Adiponectin; D016207:Cytokines; D004041:Dietary Fats; D015850:Interleukin-6; D044945:Proanthocyanidins; D002097:C-Reactive Protein; D005978:Glutathione