ABSTRACT
Objective:To investigate the levels of serum pyrolysis-related factors cysteine protease-1 (caspase-1) and interleukin-18 (IL-18) in patients with gestational diabetes mellitus (GDM) and their relationship with insulin resistance (IR) .Methods:A total of 102 GDM patients admitted to Kaifeng Traditional Chinese Medicine Hospital from Apr. 2019 to Mar. 2021 were selected as the GDM group, and 102 healthy pregnant women undergoing obstetric examination in the same period were included as the normal group. The age, gestational week, fasting insulin (FINS) , pre-pregnancy body mass index (BMI) , triglycerides (TG) , fasting blood glucose (FBG) , total cholesterol (TC) , and homeostatic model insulin resistance index (HOMA-IR) and other materials were compared between the GDM group and the normal group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum caspase-1 and IL-18; Pearson method was used to analyze the correlation between serum caspase-1 and IL-18 levels and HOMA-IR in GDM patients; Logistic regression method was used to analyze the influencing factors of GDM.Results:The levels of TG [ (2.94±0.99) mmol/L vs (2.09±0.70) mmol/L], FBG [ (5.87±1.94) mmol/L vs (4.90±1.67) mmol/L], TC [ (5.72±1.92) mmol/L vs (5.03±1.68) mmol/L], FINS [ (11.45±3.87) mIU/L vs (6.92±2.34) mIU/L], HOMA-IR [ (3.05±0.78) vs (1.51±0.40) ] and levels serum caspase-1 [ (86.27±28.78) pg/mL vs (40.98±13.54) pg/mL] and IL-18 [ (44.26±14.56) pg/L vs (30.45±10.12) pg/L] in the GDM group were higher than those in the normal group (t=7.080, 3.827, 2.731, 10.116, 17.743, 14.381, 7.866, P<0.05) ; the levels of serum caspase-1 and IL-18 in GDM patients were positively correlated with HOMA-IR ( r=0.518, 0.555, P<0.05) ; FBG, TG, FINS, HOMA-IR, caspase-1, IL-18 were risk factors affecting the occurrence of GDM (95% CI=1.578-3.826, 1.454-3.311, 1.477-3.405, 1.678-4.265, 1.406-3.141, 1.511-3.551, P<0.05) . Conclusions:The levels of serum caspase-1 and IL-18 in patients with GDM are relatively high, which are significantly related to IR. Caspase-1 and IL-18 may be potential targets for the treatment of GDM.
ABSTRACT
Objective@#To investigate the dynamic expression of hepatic carnitine palmitoyltransferase-II (CPT-II) in the mitochondrial inner membrane during hepatocyte malignant transformation induced by lipid accumulation.@*Methods@#Male Sprague-Dawley rats were divided randomly into control, fatty liver, and induced cancer groups, which were fed with normal, high-fat (HF), and HF containing 2-fluorenylacetamide (0.05%, 2-FAA) diets, respectively, for 14 weeks. One rat from each group was sacrificed every two weeks and the blood and liver samples were collected. Liver morphological changes were evaluated with hematoxylin and eosin staining, and the liver tissue samples were divided into control, fatty liver, degeneration, precancerous, and cancerous groups accordingly. Hepatic lipids were dyed by the oil red O method. The CPT-II expression was measured by immunohistochemistry and compared with the specific CPT-II concentration (ng/mg liver protein, ng/mg P) among different groups. Serum levels of circulating total cholesterol (Tch), triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were quantitatively analyzed.@*Results@#Massive lipid accumulation hepatocytes was seen in rats on HF and HF containing 2-FAA diets. The lipid levels in the control group were significantly lower than those in the fatty liver (t = -11.556, P < 0.001), degeneration (t = -4.847, P = 0.04), precancerous (t = -13.652, P = 0.005), and cancerous groups (t = -10.896, P = 0.008). The serum TG and Tch levels in the degeneration, precancerous, and cancerous groups were 2-3 times higher than those in the control group (P < 0.05). After 2-FAA treatment, the morphological changes of rat hepatocytes showed the progression from degeneration and precancerosis to cancerosis, with hepatocyte injury. The serum AST and ALT levels in the degeneration, precancerous, and cancerous groups were significantly higher (4-8 times) than those in the control group (P < 0.05). The specific concentration of liver CPT-II expression was significantly reduced during hepatocyte malignant transformation, as confirmed by immunohistochemistry, with the CPT-II levels significantly lower in the cancerous group than in any of other groups (P < 0.05).@*Conclusion@#Low hepatic CPT-II expression might lead to abnormal lipid accumulation in hepatocytes, which should promote the malignant transformation of hepatocytes.
ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse macrovesicular steatosis and excessive lipid accumulation in the liver due to nonalcoholic reasons and other specific factors for liver injury, including simple fatty liver, nonalcoholic steatohepatitis, and liver cirrhosis. With the increasing incidence of NAFLD, the risk of hepatocellular carcinoma (HCC) is also increasing, but the exact mechanism remains unknown. This paper summarizes the roles of lipid accumulation, related cells, proteins, hormones, and metabolites in malignant transformation of hepatocytes, as well as the relationship between NAFLD, HCC, and lipid metabolism, and provides a new perspective for the prevention of HCC in clinical practice.