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Correlation between PPAR-α methylation level in peripheral blood and inflammatory factors of NAFLD patients with DM
Jianghua Ju1, Qingxian Huang1, Jing Sun1
1Department of Endocrinology, Qilu Hospital of Shandong University, Qingdao, Shandong 266035, P.R. China.
Abstract:
The correlation between the methylation levels of peroxisome proliferator-activated receptor-α (PPAR-α) in the peripheral blood and the inflammatory factors associated with non-alcoholic fatty liver disease (NAFLD) patients with diabetes mellitus (DM) was investigated. Thirty-two samples of normal liver tissues (group N) and 35 samples of liver tissues from NAFLD patients with DM (group M) were used for the present study. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured using commercially available kits. The accumulation of lipid droplets and glycogen in the two groups was determined through Oil Red O staining and Sudan III staining. mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-lβ (IL-1β) and IL-6 in liver tissues of groups N and M were detected using reverse transcription-polymerase chain reaction (RT-PCR). In addition, western blotting was used to detect the protein expression of PPAR-α in liver tissues of both groups. The Statistical Product and Service Solutions (SPSS) 17.0 statistical software was used to analyze the expression difference of PPAR-α in liver tissues in the groups. The high levels of ALT and AST indicated severe liver injury in group M. Oil Red O staining and Sudan III staining showed a large number of lipid droplets and glycogen accumulation in the liver of group M patients. RT-PCR showed that the expression of inflammatory factors was extremely high and that the inflammatory injury was severe in the liver of group M patients. Western blotting showed that the expression of PPAR-α in group N was significantly higher than that in group M. ANOVA results showed that the expression of PPAR-α in liver tissues of groups N and M patients were statistically significantly different (P<0.01). Therefore, the abnormal expression of PPAR-α is closely associated with the occurrence and development of NAFLD complicated with DM, and that the abnormal expression of PPAR-α is closely related to inflammatory factors. Results from the present study suggest PPAR-α has important value in the study on NAFLD complicated with DM. The expression of PPAR-α can be used as a new basis for the diagnosis and treatment of NAFLD complicated with DM.
Insights
Abnormal peroxisome proliferator-activated receptor-α (PPAR-α) expression is linked to non-alcoholic fatty liver disease (NAFLD) in diabetic patients. Lower PPAR-α levels correlate with increased inflammation, suggesting its diagnostic and therapeutic potential.
Area of Science:
- Hepatology and Metabolic Diseases
- Molecular Biology and Genetics
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a growing concern, particularly when co-occurring with diabetes mellitus (DM).
- The role of peroxisome proliferator-activated receptor-α (PPAR-α) in the pathogenesis of NAFLD with DM requires further elucidation.
- Inflammatory factors are implicated in the progression of liver damage in NAFLD.
Purpose of the Study:
- To investigate the correlation between PPAR-α methylation levels and inflammatory factors in NAFLD patients with DM.
- To compare PPAR-α expression in normal liver tissues versus those from NAFLD patients with DM.
- To assess the potential of PPAR-α as a biomarker for NAFLD complicated with DM.
Main Methods:
- Analysis of liver tissue samples from normal (N=32) and NAFLD with DM (N=35) groups.
- Measurement of liver enzymes (ALT, AST), lipid/glycogen accumulation (Oil Red O, Sudan III staining).
- Detection of inflammatory cytokine mRNA (TNF-α, IL-1β, IL-6) via RT-PCR and PPAR-α protein expression via Western blotting.
Main Results:
- NAFLD with DM patients exhibited significantly elevated ALT and AST levels, indicating severe liver injury.
- Increased lipid droplets, glycogen accumulation, and high expression of inflammatory factors were observed in the NAFLD with DM group.
- Significantly lower PPAR-α protein expression was found in the liver tissues of NAFLD with DM patients compared to normal controls (P<0.01).
Conclusions:
- Abnormal PPAR-α expression is closely associated with the occurrence and development of NAFLD complicated with DM.
- PPAR-α expression is significantly related to inflammatory factors in the context of NAFLD and DM.
- PPAR-α holds potential as a novel diagnostic and therapeutic target for NAFLD with DM.
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