Leptin Insensitivity in NAFLD Is Produced by Oxidative Stress and Cytokine Overexpression

Nonalcoholic fatty liver disease (NAFLD) pathogenesis is caused by an imbalance in the biochemistry and immunology of the liver. The aim of the present study was to evaluate the role of oxidative stress and inflammatory factors in the serum concerning leptin concentration.

This study was carried out on 67 females, including 20 healthy and 47 patients diagnosed by liver scan. Anthropometric analysis and routine biochemical tests, including alanine and aspartate transaminase, triglycerides, cholesterol, fasting blood sugar, low-density lipoprotein, high-density lipoprotein, and their ratio, were carried out. Also, the concentration of malondialdehyde and total antioxidant capacity concentration as well as the activity of catalase, superoxide dismutase, and glutathione peroxidase, were estimated. In addition, the concentration of leptin, interleukin-6, and tumor necrosis factor-α was analyzed. Data were analyzed using one-way ANOVA followed by Tukey's post-hoc test, with P<0.05 considered statistically significant.

Patients with NAFLD had significantly higher BMI (33.63±6.37 kg/m² vs. 25.33±2.53 kg/m²), waist circumference (90.6±9.85 cm vs. 81.38±5.44 cm), and hip circumference (93.43±10.06 cm vs. 86.14±5.57 cm) compared with controls (P<0.05). Their lipid profile showed elevated triglycerides (209.12±73.41 mg/dl vs. 121.19±38.51 mg/dl) and cholesterol (229.73±43.42 mg/dl vs. 171.19±22.91 mg/dl), as well as a higher prevalence of diabetes mellitus (30%). Although total antioxidant capacity did not differ (P>0.05), MDA levels were significantly increased from controls (1.01±0.22 nmol/L) to Grade 1 (1.24±0.41 nmol/L), Grade 2 (1.33±0.32 nmol/L), and Grade 3 NAFLD (1.43±0.44 nmol/L), while SOD, CAT, and GPx activities were reduced (all P<0.05). IL 6, TNF α, and leptin concentrations were markedly elevated from grade 1 to 3, with the highest at Grade 3 (17.63±10.19 pg/mL, 104.63 ± 14.43 ng/mL, and 2.23±0.92 μg/mL, respectively, for each one; P<0.05).

Although leptin controls fat metabolism via satiety, results revealed that the overproduction of leptin might be a consequence of oxidative stress and inflammatory response to fat accumulation in the liver. Therefore, measuring leptin along with IL-6 and TNF-α might help to diagnose liver injury.