Insulin‐like growth factor binding protein 1 ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease

作者：J. Pan, Cen Li, Tianyu Zhou, Mengli Yu, Xueyang Chen, Wenxi Jiang, Youming Li, Chaohui Yu, Zhe Shen · 发表于：Journal of Gastroenterology and Hepatology · 年份：2021 · DOI：10.1111/jgh.15627 · 被引用次数：33 · 研究领域：Growth Hormone and Insulin-like Growth Factors、Liver Disease Diagnosis and Treatment、Diabetes, Cardiovascular Risks, and Lipoproteins

BACKGROUND AND AIMS: Insulin-like growth factor binding protein 1 (IGFBP1) is recently proved to be associated with glucose regulation and insulin resistance. However, little is known about its direct impact on nonalcoholic fatty liver disease (NAFLD). This study aims to investigate the effect and potential mechanism of IGFBP1 in NAFLD. METHODS: We first measured the expression level of IGFBP1 in NAFLD patients, mice, and cells. Then in in vivo study, C57BL/6 mice were fed with a methionine/choline-deficient (MCD) diet for 4 weeks to establish the model of NAFLD. And for the last 2 weeks, the mice were injected intraperitoneally with vehicle or recombinant mouse IGFBP1 0.015 mg/kg/d. The L02 cells were treated with free fatty acids (FFA) or palmitate acids (PA) and recombinant IGFBP1 for 48 h. Integrin-linked kinase (ILK) inhibitor and small interfering RNA were used to explore the potential interactions between IGFBP1 and integrin β1 (ITGB1). RESULTS: The expression of IGFBP1 was increased in NAFLD patients, mice, and cells. IGFBP1 treatment significantly ameliorated lipid accumulation and hepatic injury in MCD-fed mice. IGFBP1 downregulated hepatic lipogenesis and upregulated lipid β-oxidation. In addition, IGFBP1 attenuated the nuclear factor-kappa B (NF-κB) and extracellular regulated protein kinases (ERK) signaling pathways. In vitro, we proved that IGFBP1 relieved FFA-induced lipid accumulation via interacting with ITGB1 and alleviated inflammation by inhibiting NF-κB a...