Astaxanthin inhibits the reduction of glycolysis during the activation of hepatic stellate cells.

Abstract Aims Hepatic stellate cells (HSCs) play an essential role in the development of liver fibrosis by producing extracellular matrix proteins, growth factors, and pro-inflammatory and pro-fibrogenic cytokines once activated. We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, attenuates HSC activation. The objective of this study was to investigate whether there is a difference in glycolysis between quiescent and activated HSCs and the effect of ASTX on glycolysis during HSC activation. Materials and methods Mouse primary HSCs were activated for 7 days in the presence or absence of 25 μM of ASTX. Quiescent HSCs (qHSCs), 1 day after isolation, and activated HSCs (aHSCs) treated with/without ASTX were plated in a Seahorse XF24 cell culture microplate for Glycolysis Stress tests. Key findings aHSCs had significantly lower glycolysis, but higher glycolytic capacity, maximum capacity of glycolysis, and non-glycolytic acidification than qHSCs. Importantly, ASTX markedly increased glycolysis during HSC activation with a concomitant increase in lactate formation and secretion. Compared with qHSCs, aHSCs had significantly lower expression of glucose transporter 1, the major glucose transporter in HSCs, and its transcription factor hypoxia-inducible factor 1α, which was markedly increased by ASTX in aHSCs. Significance Our data suggest that ASTX may prevent the activation of HSCs by altering glycolysis and the expression of genes involved in the pathways.