Comparison of serum Farnesoid X Receptor (FXR) levels and their associations with obesity-related metabolic parameters: A clinical study

Abstract

Background: Farnesoid X Receptor (FXR) regulates the enterohepatic circulation of bile acids and influences nutrient metabolism. These functions position FXR as a potential therapeutic target for obesity and related conditions, although its association with BMI in healthy individuals remains inadequately defined. Objective: To investigate serum FXR levels in normal-weight, overweight, and obese individuals, considering their sociodemographic profiles, anthropometry, physical activity frequency, sleep patterns, eating behaviors, and laboratory findings. Methods: This prospective cross-sectional study included 80 healthy participants (43 women [53.75%] and 37 men [46.25%]) who presented to the Family Medicine Clinic or Nutrition and Diet Polyclinic at Bezmialem Vakıf University Faculty of Medicine Hospital between January 2024 and June 2024. Participants were categorized into four groups including 20 individuals based on body mass index (BMI); Group 1: 18.5–24.9 kg/m² (normal weight), Group 2: 25–29.9 kg/m² (overweight), Group 3: 30–34.9 kg/m² (obesity class I), Group 4: 35–39.9 kg/m² (obesity class II). Participants completed the Three-Factor Eating Questionnaire (TFEQ) to assess dietary habits. Biochemical parameters and FXR levels were analyzed from blood samples. All statistical analyses were conducted using SPSS version 26.0, with statistical significance defined as p < 0.05. Results: Gender distribution and lifestyle factors did not differ significantly between groups. Higher BMI was associated with increased levels of glucose (p = 0.018), HOMA-IR (p = 0.008), LDL (p = 0.011), triglycerides (p = 0.013), and WBC (p = 0.015). Emotional eating scores in Group 1 were significantly lower than in Group 4 (p = 0.046). The mean serum FXR level was 10.93 ± 9.56 ng/mL, with significant differences across BMI groups (p = 0.014), being higher in obese individuals. FXR levels were positively associated with a family history of obesity (p = 0.031), the use of topical agents (p = 0.024), and serum zinc levels (p = 0.025), whereas no significant associations were observed with gender (p = 0.721) or eating behavior scores (cognitive restraint, p = 0.483; uncontrolled eating, p = 0.581; emotional eating, p = 0.814). Conclusions: The observed associations between serum FXR levels and obesity-related metabolic parameters suggest that FXR may be involved in the metabolic dysregulation accompanying increased adiposity. Although experimental and translational studies have implicated FXR in glucose and lipid homeostasis, the present findings provide only preliminary clinical evidence and do not establish causality. Accordingly, FXR should be regarded as a mechanistic pathway of interest rather than a confirmed therapeutic or preventive target. Further longitudinal and interventional studies are needed to determine whether modulation of FXR activity or monitoring serum FXR levels has practical clinical relevance in obesity management.