Inhibition of Inflammatory Cytokine Expression Prevents High-Fat Diet-Induced Kidney Injury: Role of Lingonberry Supplementation

Susara Madduma Hewage; Suvira Prashar; Samir C Debnath; Karmin O; Yaw L Siow

doi:10.3389/fmed.2020.00080

Inhibition of Inflammatory Cytokine Expression Prevents High-Fat Diet-Induced Kidney Injury: Role of Lingonberry Supplementation

Front Med (Lausanne). 2020 Mar 27:7:80. doi: 10.3389/fmed.2020.00080. eCollection 2020.

Authors

Susara Madduma Hewage^{1

2}, Suvira Prashar^{1

3}, Samir C Debnath⁴, Karmin O^{1

2

5}, Yaw L Siow^{1

2

3}

Affiliations

¹ Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada.
² Department of Physiology & Pathophysiology, University of Manitoba, Winnipeg, MB, Canada.
³ Agriculture and Agri-Food Canada, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada.
⁴ Agriculture and Agri-Food Canada, St. John's Research and Development Centre, St. John's, NL, Canada.
⁵ Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada.

Abstract

Chronic low-grade inflammation is a major stimulus for progression of chronic kidney disease (CKD) in individuals consuming high-fat diet. Currently, there are limited treatment options for CKD other than controlling the progression rate and its associated complications. Lingonberry (Vaccinium vitis-idaea L.) is rich in anthocyanins with demonstrated anti-inflammatory effect. In the current study, we investigated the potential renal protective effect of lingonberry and its anthocyanin (cyanidin-3-glucoside) in high-fat diet fed obese mice and in human proximal tubular cells. Prolonged consumption of high-fat diets is strongly associated with obesity, abnormal lipid and glucose metabolism. Mice (C57BL/6J) fed a high-fat diet (62% kcal fat) for 12 weeks developed renal injury as indicated by an elevation of blood urea nitrogen (BUN) level as well as an increase in renal kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and renin expression. Those mice displayed an activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and increased expression of inflammatory cytokines-monocyte chemoattractant-1 (MCP-1), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) in the kidneys. Mice fed a high-fat diet also had a significant elevation of inflammatory cytokine levels in the plasma. Dietary supplementation of lingonberry for 12 weeks not only attenuated high-fat diet-induced renal inflammatory response but also reduced kidney injury. Such a treatment improved plasma lipid and glucose profiles, reduced plasma inflammatory cytokine levels but did not affect body weight gain induced by high-fat diet feeding. Lingonberry extract or its active component cyanidin-3-glucoside effectively inhibited palmitic acid-induced NF-κB activation and inflammatory cytokine expression in proximal tubular cells. These results suggest that lingonberry supplementation can reduce inflammatory response and prevent chronic kidney injury. Such a renal protective effect by lingonberry and its active component may be mediated, in part, through NF-κB signaling pathway.

Keywords: NF-κB; chronic kidney disease; cytokines; high-fat diet; inflammation; lingonberry.