Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala

Mol Nutr Food Res. 2015 Nov;59(11):2209-24. doi: 10.1002/mnfr.201500499. Epub 2015 Sep 3.

Abstract

Scope: Fumonisin (FB) occurs in maize and is an inhibitor of ceramide synthase (CerS). We determined the urinary FB1 (UFB1 ) and sphingoid base 1-phosphate levels in blood from women consuming maize in high and low FB exposure communities in Guatemala.

Methods and results: FB1 intake was estimated using the UFB1 . Sphinganine 1-phosphate (Sa 1-P), sphingosine 1-phosphate (So 1-P), and the Sa 1-P/So 1-P ratio were determined in blood spots collected on absorbent paper at the same time as urine collection. In the first study, blood spots and urine were collected every 3 months (March 2011 to February 2012) from women living in low (Chimaltenango and Escuintla) and high (Jutiapa) FB exposure communities (1240 total recruits). The UFB1 , Sa 1-P/So 1-P ratio, and Sa 1-P/mL in blood spots were significantly higher in the high FB1 intake community compared to the low FB1 intake communities. The results were confirmed in a follow-up study (February 2013) involving 299 women living in low (Sacatepéquez) and high (Santa Rosa and Chiquimula) FB exposure communities.

Conclusions: High levels of FB1 intake are correlated with changes in Sa 1-P and the Sa 1-P/So 1-P ratio in human blood in a manner consistent with FB1 inhibition of CerS.

Keywords: Ceramide synthase; Fumonisin; Maize; Sphinganine 1-phosphate; Urinary fumonisin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Enzyme Inhibitors / pharmacology*
  • Erythrocytes / chemistry
  • Female
  • Fumonisins / toxicity*
  • Fumonisins / urine
  • Humans
  • Lysophospholipids / blood
  • Middle Aged
  • Oxidoreductases / antagonists & inhibitors*
  • Sphingosine / analogs & derivatives
  • Sphingosine / blood
  • Zea mays / microbiology*

Substances

  • Biomarkers
  • Enzyme Inhibitors
  • Fumonisins
  • Lysophospholipids
  • sphingosine 1-phosphate
  • fumonisin B1
  • Oxidoreductases
  • dihydroceramide desaturase
  • Sphingosine