Minkyung Bae1, Yoojin Lee2, Tho X Pham2, Siqi Hu2, Young-Ki Park2, Ji-Young Lee3. 1. Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA; Department of Food and Nutrition, Changwon National University, Changwon, Gyeongsangnam-do, South Korea. 2. Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA. 3. Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA. Electronic address: ji-young.lee@uconn.edu.
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.
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.
Authors: Chrysi Koliaki; Julia Szendroedi; Kirti Kaul; Tomas Jelenik; Peter Nowotny; Frank Jankowiak; Christian Herder; Maren Carstensen; Markus Krausch; Wolfram Trudo Knoefel; Matthias Schlensak; Michael Roden Journal: Cell Metab Date: 2015-05-05 Impact factor: 27.287
Authors: Yuping Chen; Steve S Choi; Gregory A Michelotti; Isaac S Chan; Marzena Swiderska-Syn; Gamze F Karaca; Guanhua Xie; Cynthia A Moylan; Francesca Garibaldi; Richard Premont; Hagir B Suliman; Claude A Piantadosi; Anna Mae Diehl Journal: Gastroenterology Date: 2012-08-08 Impact factor: 22.682