Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Non-alcoholic fatty liver disease (NAFLD), defined as deposition of fat within hepatocytes. There is an inverse association between serum levels of adiponectin, as an important adipokine, and hepatic steatosis. Also, neuregulin-4 as a novel adipokine in energy metabolism is inversely associated with insulin resistance. Naringenin is one of the main flavonoids found in citrus species exerts beneficial biological effects including antioxidant, anti-inflammatory, antiadipogenic, weight-lowering and hepatoprotective activities.
Methods: To examine the effects of naringenin on insulin resistance, inflammation, and serum levels of neuregulin-4, the present clinical trial was carried out on forty-four patients with overweight/obesity newly diagnosed with MASLD. The patients were randomly allocated into either “Naringenin group” (receiving 200 mg/day naringenin) and “Control group" (receiving 200 mg/day methylcellulose) for four weeks. Body composition, glycemic indices, as well as serum concentrations of adiponectin and neuregulin-4 were determined at baseline and after the intervention.
Results: A marginal significant decrease in fasting serum insulin levels was found in the naringenin group (P=0.05), while there was a meaningful rise in QUICKI levels (P=0.02). However, no significant between-group differences were observed for glycemic parameters after adjusting for the possible confounders, post-intervention. Fat mass and body fat percentage decreased significantly in the intervention group compared to the control group post-intervention (P=0.043 and P=0.018, respectively). Moreover, there was a significant reduction in BMI and visceral fat level in the intervention group when compared with the placebo group (P = 0.001 and P = 0.039, respectively). There was no significant within-or between-group differences for serum levels of neuregulin-4 and adiponectin, post-intervention.
Conclusions: Naringenin supplementation could significantly decrease fat mass and body fat percentage in patients with MASLD. However, it could not significantly improve glycemic parameters as well as serum concentrations of adiponectin and neuregulin-4.
