Investigation of the relationship between İsthmin-1 protein levels and er stress and apoptosis in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a pathology characterized by lipid accumulation in the liver, occurring in the absence of chronic alcohol consumption or viral infections. The accumulation of triglycerides in the liver due to esterification leads to lipotoxicity, ER stress, oxidative stress, and inflammation, ultimately resulting in fibrosis. Isthmin-1 was identified in 2021 as an adipokine that plays an important role in glucose uptake and lipid metabolism. While this protein increases glucose uptake in adipose tissue, it inhibits lipid synthesis in hepatic tissue. It has been suggested that Isthmin-1 may play a role in various pathophysiological processes such as diabetes, obesity, and cardiovascular diseases. However, the literature on this protein is very limited. This study aims to investigate the relationship between routine tests and ER stress, apoptosis, and Isthmin-1 protein in patients with NAFLD. For this purpose, a total of 75 patients were included in the study, categorized into three groups: a control group without NAFLD, and grade-1 and grade-2 NAFLD groups based on ultrasound results. Blood samples taken from the patients were analyzed for glucose, BUN, creatinine, creatinine GFR, AST, ALT, ALP, GGT, sodium, and potassium levels using a biochemical autoanalyzer. In addition to these, routine complete blood count values were determined using a hemogram autoanalyzer. Using these values, the AST/ALT, lymphocyte/monocyte, platelet/lymphocyte, and neutrophil/lymphocyte ratios, as well as APRI and FIB4 scores, were calculated. Serum levels of GRP78, Caspase-3, and Isthmin-1 were measured using the ELISA method. The average age in the NAFLD groups was found to be higher compared to the control group. AST and ALT levels were significantly higher in both the grade-1 and grade-2 groups compared to the control group. Additionally, the GGT and AST/ALT ratios in the grade-2 group were notably higher than those in the control group. However, the levels of Caspase-3, GRP78, and Isthmin-1 did not show significant changes with the development of NAFLD. Caspase-3, GRP78, and Isthmin-1 levels were positively correlated with creatinine. Moreover, Isthmin-1 showed a positive correlation with both GRP78 (r: 0.8187; p<0.0001) and Caspase-3 (r: 0.7614; p<0.0001). Our results indicate an increase in AST, ALT, GGT, and AST/ALT ratio during the progression of NAFLD. Although Caspase-3, GRP78, and Isthmin-1 did not change significantly with disease development, Isthmin-1 was found to have a significant correlation with both Caspase-3 and GRP78.