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-a 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 (TNF alpha), 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.