LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECs

• Published in: Heliyon 2022-12, Vol.8 (12), p.e12385-e12385, Article e12385
• Main Authors: Duan, Qidang, Si, Huiling, Tian, Limin, Zhang, Na, Qiu, Jumei, Yu, Jing, Liu, Jing, Zhang, Qi
• Format: Article
• Language: English
• Subjects: AMP-activated protein kinase; AMPK; atherosclerosis; Autophagy; cytoplasm; death; fatty liver; glucose; HLSECs; HNF4α; humans; liver; low density lipoprotein; LOX-1; noninsulin-dependent diabetes mellitus; oxidation; phosphorylation
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2022.e12385

Type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) is a common cause of death. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the regulation of autophagy and associated with a variety of diseases, such as atherosclerosis, diabetes, and NAFLD. This study aimed to investigate the effect of LOX-1 on autophagy induced by high glucose levels in human liver sinusoidal endothelial cells (HLSECs) and whether it regulates autophagy through the adenosine monophosphate-activated protein kinase/hepatocyte nuclear factor 4α (AMPK/HNF4α) pathway. In this study, HLSECs cultured with high glucose medium showed increased expression of LOX-1, whereas autophagy was inhibited. High glucose levels decreased the AMPK phosphorylation, increased the HNF4α phosphorylation, and retained the HNF4α in the cytoplasm. By contrast, silencing of LOX-1 reversed the phenomenon induced by high glucose levels and restored the HNF4a localization. Taken together, our findings reveal a novel mechanism of high glucose-induced autophagy in HLSECs, namely, the LOX-1-mediated AMPK/HNF4α signaling pathway. Therefore, LOX-1 is an important target molecule for the regulation of autophagy in HLSECs. [Display omitted] LOX-1; Autophagy; HLSECs; AMPK; HNF4α.