Slavko Komarnytsky 1,2, John Overall 1,3, Mickey Wilson 1 and Debora Esposito 1,2 (2016). Diverse bioenergetic profiles of M1/M2 macrophages exposed to anthocyanins and their phenolic metabolites. The FASEB Journal, 30(1).
1 Plants for Human Health Institute, NC State University, Kannapolis, NC
2 Food, Bioprocessing and Nutrition Sciences, NC State University, Raleigh, NC
3 Davidson College, Davidson, NC
Differentiation of monocytes occurs at the site of inflammation into the pro-inflammatory (M1, glycolytic) or anti-inflammatory (M2, oxidative) phenotype. Chronic disorders associated with low-grade inflammatory responses are characterized by presence of pro-inflammatory mediators that induce the recruitment and activation of predominantly M1 macrophages in the metabolically active tissues. In this study, we show that anthocyanin-treated macrophages developed a distinct metabolic profile with respect to glycolysis versus oxidative phosphorylation, in part by increasing spare respiratory capacity and therefore shifting to mitochondria as their main source of ATP. Decreased glycolysis in anthocyanin-treated macrophages was accompanied by decrease in 2-NBDG deoxyglucose uptake and expression changes of Glut-1, Hk-1, and Hk-2 proteins involved in transmembrane glucose transport. Different effects exerted by individual anthocyanins suggested that the presence of the methylated hydroxyls on the B ring might be critical for their greater biological activity. Numerous anthocyanin metabolites significantly reduced various cytokine and chemokine biomarkers of inflammation, with syringic and ferulic acids producing the greatest effects. Similar effects were observed in the murine gastrointestinal and mesenteric adipose tissues exposed to portal circulation. These data clearly indicate that exposure of macrophages to anthocyanins and their metabolites changes cellular bioenergetics in these cells and may be partially responsible for changes in their biological function in response to chronic metabolic stress.