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Thursday 4 August 2016

Cranberry extract attenuates hepatic inflammation in high fat-fed obese mice



Abstract

Cranberry (Vaccinium macrocarpon) consumption has been associated with health beneficial effects. Non-alcoholic fatty liver disease (NAFLD) is a co-morbidity of obesity. In the present study, we investigated the effect of a polyphenol-rich cranberry extract (CBE) on hepatic inflammation in high fat-fed obese C57BL/6 J mice. Following dietary treatment with 0.8% CBE for 10 weeks, we observed no change in body weight or visceral fat mass in CBE supplemented mice compared to high fat-fed control mice. We did observe a significant decrease in plasma alanine aminotransferase (31%) and histological severity of NAFLD (33% decrease in area of involvement, 29% decrease in lipid droplet size) compared to high fat-fed controls. Hepatic protein levels of tumor necrosis factor alpha and C-C chemokine ligand 2 were reduced by 28% and 19%, respectively, following CBE supplementation. CBE significantly decreased hepatic mRNA levels of toll-like receptor 4 (TLR4, 63%) and nuclear factorκB (NFκB, 24%), as well as a number of genes related to the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome. In conclusion, CBE reduced NAFLD and hepatic inflammation in high fat-fed obese C57BL/6 J mice. These effects appear to be related to mitigation of TLR4-NFκB related signaling, however further studies into the underlying mechanisms of these hepatoprotective effects are needed.

Abbreviations

  • ALT, alanine aminotransferase;
  • CASP1, caspase 1;
  • CBE, polyphenol-rich cranberry extract;
  • CCL2, chemokine (C-C motif) ligand 2;
  • CCR2, C-C chemokine receptor type 2;
  • COX-2, cyclooxygenase 2;
  • DP, degree of polymerization;
  • EMR1, EGF-like module-containing mucin-like hormone receptor-like 1;
  • HF, high fat diet;
  • HOMA-IR, homeostatic model assessment-insulin resistance;
  • IL-1β, interleukin 1β;
  • MCP-1, monocyte chemotactic protein 1;
  • MIP-1α, macrophage inflammatory protein 1α;
  • NAFLD, non-alcoholic fatty liver disease;
  • NASH, non-alcoholic steatohepatitis;
  • NFκB, nuclear factor κB;
  • NLRP3, NACHT, LRR and PYD domains-containing protein 3;
  • NOS2, inducible nitric oxide;
  • PAC, proanthocyanidin;
  • ROS, reactive oxygen species;
  • TLR4, toll like receptor 4;
  • TNFα, tumor necrosis factor α;
  • TXNIP, thioredoxin interacting protein;
  • UCP2, uncoupling protein 2

Keywords

  • Vaccinium macrocarpon;
  • cranberry;
  • non-alcoholic fatty liver disease;
  • inflammation;
  • polyphenols
Funding Source: This study was supported in part by grant from the National Institutes of Health (No. AT004678) and a United States Department of Agriculture Hatch Project (No. 4565) to JDL. SLG was supported by a United States Department of Agriculture National Needs Fellowship.
Corresponding author at: Department of Food Science, The Pennsylvania State University, 332 Rodney A. Erickson Food Science Building, University Park, PA 16802. Tel.: +1 814 865 5223; fax: + 1 814 863 6132.