Insulin resistance modulates iron-related proteins in adipose tissue.
OBJECTIVE Circulating markers of iron overload are associated with insulin resistance. Less is known about the impact of iron overload on adipose tissue (AT). We hypothesized that gene expression markers of iron metabolism in AT could be associated with insulin action. RESEARCH DESIGN AND METHODS The AT expression of ferroportin (SLC40A1), transferrin (TF), TF receptor (TFRC), ferritin (FT) heavy polypeptide 1 (FTH1), and FT light polypeptide (FTL) was analyzed cross-sectionally in three independent cohorts and also after weight loss-induced changes in insulin sensitivity (clamp M value) in an independent fourth cohort. RESULTS In human AT, TF mRNA and protein levels were decreased with obesity and insulin resistance in the three cohorts and were positively associated with adipogenic mRNAs and insulin action. Otherwise, FTL mRNA and protein and SLC40A1 transcripts were positively associated with BMI and negatively linked to adipogenic genes and insulin action. Bariatric surgery-induced weight loss led to increased TF and decreased TFRC, FTH1, FTL, and SLC40A1 in subcutaneous AT in parallel to improved insulin action. CONCLUSIONS These results suggest that iron overload impacts on AT in association with insulin resistance.
Corresponding author: José Manuel Fernández-Real, jmfreal@idibgi.org.
José María
JM
Moreno-Navarrete
Marta G
MG
Novelle
Victoria
V
Catalán
Francisco
F
Ortega
Maria
M
Moreno
Javier
J
Gomez-Ambrosi
Gemma
G
Xifra
Marta
M
Serrano
Ester
E
Guerra
Wifredo
W
Ricart
Gema
G
Frühbeck
Carlos
C
Diéguez
José Manuel
JM
Fernández-Real
D000328:Adult; D050110:Bariatric Surgery; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D033862:Iron-Binding Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism*; D015431:Weight Loss
D007328:Insulin; D033862:Iron-Binding Proteins; D011990:Receptors, Transferrin