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Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet.

ABSTRACT: Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune cells, its activation regulating inflammatory cytokines and chemotactic factor secretion. Recently, a Lox-1 truncated protein isoform lacking the ox-LDL binding domain named LOXIN has been described. We have previously shown that LOXIN overexpression blocked Lox-1-mediated ox-LDL internalization in human endothelial progenitor cells in vitro. However, the functional role of LOXIN in targeting inflammation or tissue injury in vivo remains unknown. In this study, we investigate whether LOXIN modulated the expression of Lox-1 and reduced the inflammatory response in a high-fat-diet mice model. Results indicate that human LOXIN blocks Lox-1 mediated uptake of ox-LDL in H4-II-E-C3 cells. Furthermore, in vivo experiments showed that overexpression of LOXIN reduced both fatty streak lesions in the aorta and inflammation and fibrosis in the liver. These findings were associated with the down-regulation of Lox-1 in endothelial cells. Then, LOXIN prevents hepatic and aortic tissue damage in vivo associated with reduced Lox-1 expression in endothelial cells. We encourage future research to understand better the underlying molecular mechanisms and potential therapeutic use of LOXIN.

SUBMITTER: Reyes C

PROVIDER: S-EPMC9266330 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Blue honeysuckle (BH, Lonicera caerulea) is used as a traditional medicine in Russia, Japan and China, but is not commonly considered as an edible berry in Europe, USA or Korea. BH has been revealed to decrease serum cholesterol and triacylglycerol (triglyceride or TG) levels through the activation of AMP‑activated protein kinase (AMPK), thus it is expected to be a health functional food and pharmaceutical agent for the prevention of non‑alcoholic liver damage, in addition to effects as a suppressor of hyperlipidemia and as an anti‑obesity agent. In the present study, the pharmacological activity of BH extract (BHe) was observed in high‑fat diet (HFD)‑fed mice. Significant increases in fat pad weight, body weight, fat accumulation (body and abdominal fat density, and thickness of the periovarian and abdominal wall) and serum biochemical levels (aspartate transaminase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ‑glutamyltransferase, total cholesterol, low‑density lipoprotein and TG, with the exception of high‑density lipoprotein) were observed in HFD‑fed mice. In addition, increases in adipocyte hypertrophy, the area of steatohepatitis and hepatocyte hypertrophy were observed, whereas decreased zymogen content was identified upon histopathological observation. Increased deterioration of the endogenous antioxidant defense system (liver catalase, glutathione and superoxide dismutase) and hepatic lipid peroxidation was observed. In addition, there were decreases in hepatic glucokinase activity, AMPKα1 and AMPKα2 mRNA expression, adipose tissue uncoupling protein 2 expression, and adiponectin mRNA expression, increases in phosphoenolpyruvate carboxykinase and glucose‑6‑phosphatase activity, hepatic acetyl‑CoA carboxylase 1 mRNA expression, and the expression of leptin, CCAAT/enhancer‑binding protein (C/EBP) α, C/EBPβ and sterol‑regulatory‑element‑binding protein 1c mRNA in the periovarian tissue. Furthermore, non‑alcoholic fatty liver disease (NAFLD) and obesity were significantly inhibited by the continuous administration of BHe for 84 days. These results revealed that BHe may be a promising novel drug or functional food candidate for the treatment of obesity and NAFLD.

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Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet.

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