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Depression: 21st Century Solutions + The Dark Side of Wheat

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Article Publish Status: FREE
Abstract Title:

Betulinic acid is a PPARγ antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis.

Abstract Source:

Sci Rep. 2017 Jul 18 ;7(1):5777. Epub 2017 Jul 18. PMID: 28720829

Abstract Author(s):

Gloria Brusotti, Roberta Montanari, Davide Capelli, Giulia Cattaneo, Antonio Laghezza, Paolo Tortorella, Fulvio Loiodice, Franck Peiretti, Bernadette Bonardo, Alessandro Paiardini, Enrica Calleri, Giorgio Pochetti

Article Affiliation:

Gloria Brusotti

Abstract:

PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, and they serve as an alternative treatment for metabolic diseases. In this work, an affinity-based bioassay was found to be effective for selecting PPAR ligands from the dried extract of an African plant (Diospyros bipindensis). Among the ligands, we identified betulinic acid (BA), a compound already known for its anti-inflammatory, anti-tumour and antidiabetic properties, as a PPARγ and PPARα antagonist. Cell differentiation assays showed that BA inhibits adipogenesis and promotes osteogenesis; either down-regulates or does not affect the expression of a series of adipogenic markers; and up-regulates the expression of osteogenic markers. Moreover, BA increases basal glucoseuptake in 3T3-L1 adipocytes. The crystal structure of the complex of BA with PPARγ sheds light, at the molecular level, on the mechanism by which BA antagonizes PPARγ, and indicates a unique binding mode of this antagonist type. The results of this study show that the natural compound BA could bean interesting and safe candidate for the treatment of type 2 diabetes and bone diseases.

Study Type : In Vitro Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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