Mediating Roles of hsCRP, TNF-α and Adiponectin on the Associations between Body Fat and Fatty Liver Disease among Overweight and Obese Adults

SIMPLE SUMMARY: Body fat has been reported to be related to a higher risk of fatty liver disease (FLD). However, few studies have explored the mediating roles of inflammatory biomarkers or adipokines on the relationships. This study examined the potential mediating effects of high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and adiponectin (APN) in relationships between body fat and FLD in overweight and obese adults. Additionally, gender and age differences were demonstrated. It was concluded that hsCRP has a significant mediating effect on the association between body fat percentage and FLD in females independent of potential covariates. It was also demonstrated that the mediation effect of hsCRP was only significant and more profound in relatively older adults (36–56 years, 38.3%), not significant in the young ones (19–35 years). TNF-α and APN were not significantly associated with body fat percentage or FLD, with no mediating effect on the association between body fat percentage and FLD observed in either gender. In conclusion, hsCRP was a potential mediator on the association between adiposity and FLD, and this mediation is gender-specific and age-specific. The authors hope that the findings could contribute to the further exploration of the inflammatory-related mechanism of obesity-associated FLD. ABSTRACT: Body fat has been reported to be associated with a higher risk of fatty liver disease (FLD). However, few studies have explored the mediating roles of an inflammatory biomarker or adipokine on the relationships. Here, we examined the potential mediating roles of high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and adiponectin (APN) in relationships between body fat and FLD in overweight and obese adults. Additionally, gender differences will be investigated. In total, 1221 participants aged 19–56 years were included in our study. Body fat percentage was measured with Dual Energy X-ray Absorptiometry (DEXA) and FLD by abdominal ultrasound. Mediation analysis was performed to assess the mediating effect of hsCRP, TNF-α and APN on the associations between BF (%) and FLD by gender differences. We found that hsCRP was significantly associated with body fat percentage in both genders (b = 0.2014, p < 0.0001 and b = 0.1804, p < 0.0001 for male and female, respectively), while hsCRP was associated with FLD only in the female group (b = 0.1609, p = 0.0109) but not in male group (b = 0.4800, p = 0.0603). We observed that hsCRP has a significant mediating effect on the association between body fat percentage and FLD (b = 0.0290, p = 0.0201, mediation ratio: 13.6%) in the female group independent of potential covariates (age, smoking, alcohol drinking and physical activity). TNF-α was not significantly associated with body fat percentage or FLD, with no mediating effect on the association between body fat percentage and FLD in either gender. In conclusion, there is a gender-specific mediation role of hsCRP in the association between body fat and FLD. HsCRP was a potential mediator on the association between adiposity and FLD in the female gender, but not in the male gender. Higher body fat was associated with a higher risk of FLD, and the inflammation level might play a potential mediating role in the association between body fat and FLD among female overweight and obese adults.