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Strontium Alleviates Endoplasmic Reticulum Stress in a Nonalcoholic Fatty Liver Disease Model

Journal of Medicinal Food 2018년 21권 12호 p.1228 ~ 1237
Jiang Huiling, Guan Qiaowei, Xiao Yewei, Feng Zhiqiang, Yu Guang, Pan Qiangwen,
소속 상세정보
 ( Jiang Huiling ) - Southwest Medical University Department of Physiology
 ( Guan Qiaowei ) - Shaoguan University Medical College Department of Basic Medicine
 ( Xiao Yewei ) - Southwest Medical University Department of Physiology
 ( Feng Zhiqiang ) - Southwest Medical University Department of Physiology
 ( Yu Guang ) - Southwest Medical University Department of Physiology
 ( Pan Qiangwen ) - Southwest Medical University Department of Physiology

Abstract


The purpose of this study was to explore the effects of strontium on fatty liver, and to clarify the possible mechanisms by which strontium improves nonalcoholic fatty liver disease (NAFLD). We also evaluated how strontium affected the endoplasmic reticulum stress (ERS) pathways. We established an in vitro model of NAFLD using a human hepatocyte cell line (L02) treated with 0.2?mM palmitic acid. The Sprague-Dawley rats were fed with a high-fat diet (HFD) to establish NAFLD model in vivo. After strontium treatment, the total cholesterol (TC), triglyceride (TG), and lipid deposition in L02 cells and liver tissues were determined. Strontium treatment suppressed intracellular TC and TG levels and lipid accumulation in L02 cells, and the effect of high concentrations of strontium were more obvious. Strontium significantly reduced the mRNA and protein expression of glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1), SREBP cleavage activator protein (SCAP), sterol regulatory element binding protein 1c (SREBP-1c), and SREBP-2 in L02 cells. In HFD-fed rats, strontium treatment reduced serum TC, TG, and low density lipoprotein cholesterol (LDL-C) levels, concurrent with a decrease in hepatic lipid accumulation. Furthermore, strontium treatment reduced the expression of GRP78 and SREBP-2 protein in liver tissues. Overall, strontium alleviated hepatic steatosis by decreasing ERS-related protein expression in vivo and in vitro models. The results indicated that strontium has the potential to become a new therapy for the prevention and treatment of NAFLD.

키워드

endoplasmic reticulum stress; nonalcoholic fatty liver disease; strontium; unfolded protein response

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