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


Madduma Hewage, S., Prashar, S., Debnath, S.C., Karmin, O., Siow, Y.L. (2020). Inhibition of Inflammatory Cytokine Expression Prevents High-Fat Diet-Induced Kidney Injury: Role of Lingonberry Supplementation. Frontiers in Medicine, [online] 7

Plain language summary

When individuals regularly consume high-fat diet, they can develop chronic kidney disease. Chronic kidney disease is also a frequent complication resulting from uncontrolled diabetes. Currently, treatment options for chronic kidney disease patients are limited. These options are to control the progression rate of the disease and its associated complications. This study presents an alternative approach to the management of chronic kidney disease. We used a mouse model of kidney injury where a group of mice was fed a high-fat diet for 12 weeks. Their kidney function and kidney-related blood tests were measured after this feeding period. These high-fat consuming mice became obese and had abnormal levels of fat and glucose in their blood. In addition, they had high levels of kidney disease indicators and inflammation-promoting molecules, damaging the function of their kidneys. In another group of mice that were fed the same diet with added lingonberry, their test results and kidney functions were substantially improved. Lingonberry supplementation did not affect body weight. This study provides evidence for the potential use of an agri-food product to address chronic kidney disease, a global public health burden.


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.