Background: The hypothalamic feeding circuit is highly vulnerable to obesity-inducing diets, as observed in diet-induced obesity (DIO) models. Programmed cell death factor 4 (PDCD4) is widely expressed in various tissues and organs. Depending on the context, it exhibits both pro-inflammatory and anti-inflammatory properties. This study aimed to analyze serum PDCD4 levels and investigate its correlation with hypothalamic inflammation in obesity.

Methods: A total of 195 participants were separated into two groups according to their body mass index (BMI): normal weight group (18.5 kg/m² ≤ BMI < 24 kg/m²) and obesity group (BMI ≥28 kg/m²). Serum levels of the following were measured using enzyme-linked immunosorbent assay (ELISA): PDCD4, neuropeptide Y (NPY), Ionized calcium-binding adapter molecule 1 (Iba1), and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3). Other biochemical indicators were analyzed. Statistical analyses were performed to evaluate the association between serum PDCD4 levels and other biochemical indicators.

Results: A significant increase in serum PDCD4 level was evident in the obesity group compared with the control group. A binary logistic regression analysis revealed a statistically significant relationship between PDCD4 and obesity (p < 0.05). Based on Spearman correlation analysis, a positive correlation was found between the serum PDCD4 level and BMI, and the serum PDCD4 level was positively correlated with NPY, Iba1 and NLRP3 levels (p < 0.05). Furthermore, serum PDCD4 level was found to be independently associated with Iba1 and NLRP3, indicating the role of PDCD4 in regulating hypothalamic inflammation in the obesity context.

Conclusion: In addition to a significant elevation in obese patients, serum PDCD4 level is independently correlated with Iba1 and NLRP3 levels, suggesting a mediating role of PDCD4 in the activation of Iba1 and NLRP3, which is crucial for facilitating peripheral-to-central inflammatory crosstalk and ultimately the occurrence of hypothalamic inflammation.