ROS Modulating Effects of Lingonberry (Vaccinium vitis-idaea L.) Polyphenols on Obese Adipocyte Hypertrophy and Vascular Endothelial Dysfunction

Abstract

Oxidative stress and dysregulated adipocytokine secretion accompanying hypertrophied adipose tissue induce chronic inflammation, which leads to vascular endothelial dysfunction. The present study investigated the ability of anthocyanin (ACN) and non-anthocyanin polyphenol (PP) fractions from lingonberry fruit to mitigate adipose tissue hypertrophy and endothelial dysfunction using 3T3-L1 adipocytes and human umbilical vein endothelial cells (HUVECs). This study showed that the PP fraction decreased intracellular ROS generation in hypertrophied adipocytes by enhancing antioxidant enzyme expression (SOD2) and inhibiting oxidant enzyme expression (NOX4, iNOS). Moreover, PP and ACN fractions reduced triglyceride content in adipocytes accompanied by downregulation of the expression of lipogenic genes such as aP2, FAS, and DAGT1. Treatment with both fractions modulated the mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression and secretion of leptin and adiponectin were, respectively, down- and upregulated. Furthermore, PP and ACN fractions alleviated the inflammatory response in TNF-α-induced HUVECs by inhibiting the expression of pro-inflammatory genes (IL-6, IL-1β) and adhesion molecules (VCAM-1, ICAM-1, SELE). The obtained results suggest that consuming polyphenol-rich lingonberry fruit may help prevent and treat obesity and endothelial dysfunction due to their antioxidant and anti-inflammatory actions.

Lingonberry (Vaccinium vitis-idaea L.) Fruit as a Source of Bioactive Compounds with Health-Promoting Effects—A Review

“…Hypertrophied adipocytes treated with anthocyanin and non-anthocyanin polyphenol fractions from lingonberry fruit accumulated fewer lipids and had a reduced triglyceride (TG) content. This was accompanied by the downregulated expression of the lipogenic genes involved in fatty acid and TG syntheses, such as adipocyte protein 2 (aP2), fatty acid synthase (FAS), and diacylglycerol acyltransferase-1 (DGAT1) [ 40 ]. Furthermore, in TNF-α-induced human umbilical vein endothelial cells (HUVECs), polyphenol fractions attenuated the inflammatory response by inhibiting the expression of pro-inflammatory genes (IL-6, IL-1β) and adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and selectin E (SELE) [ 40 ].…”

“…This was accompanied by the downregulated expression of the lipogenic genes involved in fatty acid and TG syntheses, such as adipocyte protein 2 (aP2), fatty acid synthase (FAS), and diacylglycerol acyltransferase-1 (DGAT1) [ 40 ]. Furthermore, in TNF-α-induced human umbilical vein endothelial cells (HUVECs), polyphenol fractions attenuated the inflammatory response by inhibiting the expression of pro-inflammatory genes (IL-6, IL-1β) and adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and selectin E (SELE) [ 40 ]. The crude extract (CE) and a polyphenol-rich fraction (PRF) from lingonberry were investigated for anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages.…”

Vaccinium vitis-idaea L. Fruits: Chromatographic Analysis of Seasonal and Geographical Variation in Bioactive Compounds

“…The high content of these constituents is thought to be linked to antioxidant, anti-inflammatory, antiproliferative, antimicrobial, antiobesity, and hepatoprotective properties of lingonberries. Therefore, they are increasingly marketed as a natural solution for the urinary tract and digestive health [18][19][20]. Lingonberry components are regarded as promising lead compounds for multi-targeting pharmaceuticals and nutraceuticals of natural origin [21].…”

Phenological and Geographical Effects on Phenolic and Triterpenoid Content in Vaccinium vitis-idaea L. Leaves

“…Lingonberry is extremely hardy, tolerating cold climate, drought, and diverse habitats-from exposed, dry slopes and peat soils to ombrotrophic bogs [1][2][3][4]. Fruits of lingonberry are gaining notoriety as "superfoods", because of health benefits deriving from their consumption and their significant economic importance [5]. However, due to the limited seasonal availability of fresh fruits, leaves have been proposed as a potential alternative raw material for functional foods [6].…”