S100A9 extends lifespan in insulin deficiency

Giorgio Ramadori (), Sanda Ljubicic, Serena Ricci, Despoina Mikropoulou, Xavier Brenachot, Christelle Veyrat-Durebex, Ebru Aras, Rafael M. Ioris, Jordi Altirriba, Elisabeth Malle, Dirk Foell, Thomas Vogl and Roberto Coppari ()
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Giorgio Ramadori: University of Geneva
Sanda Ljubicic: University of Geneva
Serena Ricci: University of Geneva
Despoina Mikropoulou: University of Geneva
Xavier Brenachot: University of Geneva
Christelle Veyrat-Durebex: University of Geneva
Ebru Aras: University of Geneva
Rafael M. Ioris: University of Geneva
Jordi Altirriba: University of Geneva
Elisabeth Malle: University of Geneva
Dirk Foell: University of Munster
Thomas Vogl: University of Munster
Roberto Coppari: University of Geneva

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Tens of millions suffer from insulin deficiency (ID); a defect leading to severe metabolic imbalance and death. The only means for management of ID is insulin therapy; yet, this approach is sub-optimal and causes life-threatening hypoglycemia. Hence, ID represents a great medical and societal challenge. Here we report that S100A9, also known as Calgranulin B or Myeloid-Related Protein 14 (MRP14), is a leptin-induced circulating cue exerting beneficial anti-diabetic action. In murine models of ID, enhanced expression of S100A9 alone (i.e. without administered insulin and/or leptin) slightly improves hyperglycemia, and normalizes key metabolic defects (e.g. hyperketonemia, hypertriglyceridemia, and increased hepatic fatty acid oxidation; FAO), and extends lifespan by at least a factor of two. Mechanistically, we report that Toll-Like Receptor 4 (TLR4) is required, at least in part, for the metabolic-improving and pro-survival effects of S100A9. Thus, our data identify the S100A9/TLR4 axis as a putative target for ID care.

Date: 2019
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DOI: 10.1038/s41467-019-11498-x

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