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New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver

Nicolas Loiseau1, Arnaud Polizzi, Aude Dupuy

  • 1INRA, UMR1331 Toxalim, Research Centre in Food Toxicology, 31027, Toulouse, France, Nicolas.Loiseau@toulouse.inra.fr.

Archives of Toxicology
|August 27, 2014
PubMed

Insights

Fumonisin B1 (FB1) toxin affects sphingolipid biosynthesis by inhibiting ceramide synthases (CerS). Its organ-specific toxicity in piglets is linked to differential interactions with CerS isoforms, impacting lung and liver ceramide levels.

Area of Science:

  • Biochemistry
  • Toxicology
  • Molecular Biology

Background:

  • Fumonisin B1 (FB1) inhibits sphingolipid biosynthesis by targeting ceramide synthases (CerS).
  • FB1 causes multi-organ dysfunction in mammals, but the molecular mechanism of CerS inhibition is unclear.
  • Mammalian CerS exist as six isoforms with tissue-specific expression, suggesting a role in FB1's organ specificity.

Purpose of the Study:

  • To investigate the molecular mechanism behind Fumonisin B1's organ-specific toxicity.
  • To determine how FB1 affects different ceramide synthase (CerS) isoforms in vivo.
  • To elucidate the relationship between FB1 exposure, CerS activity, and sphingolipid profiles in lung and liver tissues.

Main Methods:

  • Piglets were exposed to Fumonisin B1 (1.5 mg/kg/day for 9 days).
  • Sphingolipid content (ceramides and sphingomyelins) was analyzed in lung and liver tissues.
  • The effects on individual ceramide synthase (CerS) isoforms were deduced from changes in specific ceramide and sphingomyelin species.

Main Results:

  • Total ceramide levels decreased by 50% in the lungs but increased 3.5-fold in the livers of FB1-exposed piglets.
  • FB1 preferentially inhibited CerS4 and CerS2, leading to ceramide depletion in the lungs.
  • FB1 interacted with CerS1, CerS2, and CerS4 to alter ceramide profiles, enriching d18:1/C20:0 and d18:1/C22:0 ceramides in the liver and d18:1/C18:0 ceramides via CerS1.

Conclusions:

  • The tissue-specific effects of Fumonisin B1 are attributed to its differential interactions with CerS4, CerS2, and CerS1.
  • FB1's impact on ceramide synthase isoforms explains its distinct toxicological outcomes in different organs.
  • Understanding these molecular interactions is crucial for predicting and mitigating FB1 toxicity.

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