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.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Chacón
M R
MR
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas, University Hospital of Tarragona Joan XXIII, Pere Virgili Institute, Universitat Rovira i Virgili, Tarragona, Spain.
Miranda
M
M
Jensen
C H
CH
Fernández-Real
J M
JM
Vilarrasa
N
N
Gutiérrez
C
C
Näf
S
S
Gomez
J M
JM
Vendrell
J
J
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D054392:Adipokines / Q000032:analysis / Q000378:metabolism; D000328:Adult; D050110:Bariatric Surgery; D002135:Calcium-Binding Proteins; D002460:Cell Line; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins / Q000097:blood* / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood* / Q000276:immunology; D009767:Obesity, Morbid / Q000097:blood / Q000276:immunology; D050177:Overweight / Q000097:blood / Q000276:immunology; D011184:Postoperative Period
D054392:Adipokines; D002135:Calcium-Binding Proteins; D016207:Cytokines; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins