Serum hepcidin levels are associated with obesity but not liver disease

Abstract

Objective: Hepcidin is regulated by anemia and inflammation. It is primarily expressed in the liver but studies have reported its expression in adipose tissue. The relationship between BMI and serum hepcidin and the relationship between liver histology and serum hepcidin in the morbidly obese was investigated.

Methods: Serum and liver tissue from patients undergoing bariatric surgery (bariatric cohort, n = 105) and serum from healthy blood donors (n = 60) were used to conduct this study. Serum hepcidin was measured using sandwich ELISA, highly specific for hepcidin-25. Serum ferritin, IL-6, IL-1β and liver function biochemistries were also measured.

Results: After controlling for covariates, BMI ≥ 35 kg/m(2) was significantly associated with higher serum hepcidin level compared to individuals with lower BMI groups (17.7 ± 11.5 vs. 3.3 ± 4.7 ng/ml, P = 0.002). The presence of NAFLD was not associated with higher serum levels of hepcidin (multivariate P = 0.37). There was no association between serum hepcidin levels and liver histology (presence of steatohepatitis, advanced fibrosis, or NAFLD activity score) in the bariatric cohort.

Conclusions: Obesity, but not the presence of NAFLD was associated with serum hepcidin levels. There was no association between serum hepcidin and liver histology in the morbidly obese undergoing bariatric surgery.

Figure1

The study participants were stratified based on International Classification of adult overweight and obesity according to BMI cut-off points: Normal range <25 (n=14); Overweight: 25-29.9 (n=22); Obese class I: 30-34.9 (n=16); Obese class II: 35-39.9 (n=24); and Obese class III ≥40 (n=89) as per the WHO 1998 classification. ANOVA showed a significant relationship between BMI and serum hepcidin levels (P<0.001). Post-hoc multiple comparison test showed significantly higher serum hepcidin levels in the obesity class II and III (BMI ≥ 35) compared to individuals with normal BMI and obesity class 1 (P<0.001). There was no difference between obesity classes II and III (P=1.0).

Figure2

Significant correlation between serum hepcidin level and BMI as a continuous variable (r=0.51, P<0.001).

Figure3

Individuals with NAFLD in bariatric cohort (n=57) were categorized based on the histological severity into hepatic steatosis (n=13), NASH with no evidence of fibrosis (n=20) and NASH with any fibrosis (F1-F4) (n=24). Serum ferritin (P=0.013) was statistically significantly higher in NASH with fibrosis group (Figure 3 A) compared to the other subgroups. However, levels of serum hepcidin in these subgroups were not significantly different (Figure 3B).