Human Serum Levels of Fetal Antigen 1 (FA1/Dlk1) Increase with Obesity, Are Negatively Associated with Insulin Sensitivity and Modulate Inflammation in Vitro

Objective: To investigate fetal antigen 1 (FA1) protein within the context of human obesity and its relation with insulin sensitivity.

Subjects: Cross-sectional study that analyses circulating levels of FA1 in two selected human cohorts: n=127 men for the study of FA1 circulating levels in the context of obesity and insulin sensitivity (S(i)); and n=61 severely obese women before and after bariatric surgery. The response in vitro to FA1 protein on human cell lines of monocytes, preadipocytes and mature adipocytes was studied.

Measurements: Anthropometrical parameters: body mass index, waist-to-hip ratio, waist circumference, fat-free mass and fat mass. Clinical parameters: lipid profile (high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides), glycemic profile (fasting glucose, insulin, S(i), HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), cytokines (sIL-6), adipokines (adiponectin) and circulating soluble fractions of tumor necrosis factor-alpha receptors 1 and 2 (sTNFR1 and sTNFR2).

Results: IN the obesity study, levels of FA1 in serum were found to increase with obesity. The S(i) index was negatively dependent on FA1 levels. In severe obesity, serum levels of FA1 decreased 1.4-fold 6 months after bariatric surgery. In vitro assays with FA1 protein on human monocytes and adipocytes cell lines modified the expression of pro-inflammatory cytokines and adipokines (tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), IL-6 (interleukin-6) and adiponectin).

Conclusion: FA1 serum levels were increased in obese subjects and might influence S(i). The stimulatory effect of FA1 protein on pro-inflammatory cytokines on both immune and adipose cell types could contribute to worsening the inflammatory environment observed in obesity.