Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest

寻找外来代谢物的目标:从海洋害虫中获取新型过氧化物酶体增殖激活受体 (PPAR) 激动剂

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作者:Rosa Maria Vitale, Enrico D'Aniello, Stefania Gorbi, Andrea Martella, Cristoforo Silvestri, Maria Elisa Giuliani, Tariq Fellous, Alessandra Gentile, Marianna Carbone, Adele Cutignano, Laura Grauso, Laura Magliozzi, Gianluca Polese, Biagio D'Aniello, Fanny Defranoux, Serena Felline, Antonio Terlizzi,

Abstract

Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)-a bioactive component of the green alga Caulerpa cylindracea that has invaded the entire Mediterranean basin-is an agonist of peroxisome proliferator-activated receptors (PPARs). Our interdisciplinary study started with the in silico prediction of the ligand-protein interaction, which was then validated by in vivo, ex vivo and in vitro assays. On the basis of these results, we candidate CAU as a causal factor of the metabolic and behavioural disorders observed in Diplodus sargus, a native edible fish of high ecological and commercial relevance, feeding on C. cylindracea. Moreover, given the considerable interest in PPAR activators for the treatment of relevant human diseases, our findings are also discussed in terms of a possible nutraceutical/pharmacological valorisation of the invasive algal biomasses, supporting an innovative strategy for conserving biodiversity as an alternative to unrealistic campaigns for the eradication of invasive pests.

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