Lingonberry (Vaccinium vitis-idaea L.) supplementation protects against chronic kidney disease and improves fatty liver

Abstract

Chronic kidney disease (CKD) is the structural or functional loss of the kidney over time. Unless properly managed, it would progress to its final stage, end-stage renal disease (ESRD). Chronic low-grade inflammation caused by lipotoxicity is a central pathological mediator of nephron damage in obesity-related CKD. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor of CKD and a commonly observed complication in obese CKD patients. Impaired hepatic lipid metabolism is a hallmark of NAFLD. NAFLD triggers lipotoxicity and systemic inflammation, further aggravating the progression of CKD. Therefore, attenuation of nephron injury caused by lipotoxicity-triggered inflammation and reduction of dyslipidemia by improving fatty liver and hepatic lipid metabolism might be pertinent strategies in managing obesity-related CKD.

Lingonberry (Vaccinium vitis-idaea L.) is an anthocyanin-rich berry with promising antioxidant, anti-inflammatory, and lipid-lowering properties. The general objective of this project was to investigate the effect of Manitoba wild lingonberry supplementation on high-fat diet (HFD) induced CKD and impaired hepatic lipid metabolism in C57BL/6J male mice. Supplementation of Manitoba wild lingonberry powder (5% w/w) significantly reduced HFD-induced kidney damage and renal inflammation. Further, pretreatment of renal proximal tubular cells (HK-2) with lingonberry extract significantly diminished palmitic acid-induced expression of inflammatory cytokines inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling.

Lingonberry supplementation improved fatty liver by reducing plasma and liver lipid levels, hepatic injury and inflammation, and strengthening hepatic antioxidant defense by restoring nuclear factor-erythroid factor 2-related factor 2 (Nrf2)/glutathione (GSH) signaling. Notch signaling has been identified as an important mediator of hepatic lipid metabolism and its activation is associated with NAFLD. Lingonberry attenuated HFD-induced expression of Notch1 and elevated genes related to fatty acid b-oxidation in the liver and hepatocytes (HepG2). Further, cyanidin-3-glucoside, an anthocyanin found in lingonberry, could be one of the potential bioactive compounds responsible for the observed reno- and hepatoprotective effects. Taken together, the results of this thesis suggest that regular consumption of lingonberry might be an effective alternative treatment option to prevent CKD and improve NAFLD in obese individuals.