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  • Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster.

Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster.

The Journal of nutritional biochemistry (2015-08-26)
Elizabeth L Cordonier, Riem Adjam, Daniel Camara Teixeira, Simone Onur, Richard Zbasnik, Paul E Read, Frank Döring, Vicki L Schlegel, Janos Zempleni
ABSTRACT

Holocarboxylase synthetase (HLCS) is the sole protein-biotin ligase in the human proteome. HLCS has key regulatory functions in intermediary metabolism, including fatty acid metabolism, and in gene repression through epigenetic mechanisms. The objective of this study was to identify food-borne inhibitors of HLCS that alter HLCS-dependent pathways in metabolism and gene regulation. When libraries of extracts from natural products and chemically pure compounds were screened for HLCS inhibitor activity, resveratrol compounds in grape materials caused an HLCS inhibition of >98% in vitro. The potency of these compounds was piceatannol>resveratrol>piceid. Grape-borne compounds other than resveratrol metabolites also contributed toward HLCS inhibition, e.g., p-coumaric acid and cyanidin chloride. HLCS inhibitors had meaningful effects on body fat mass. When Drosophila melanogaster brummer mutants, which are genetically predisposed to storing excess amounts of lipids, were fed diets enriched with grape leaf extracts and piceid, body fat mass decreased by more than 30% in males and females. However, Drosophila responded to inhibitor treatment with an increase in the expression of HLCS, which elicited an increase in the abundance of biotinylated carboxylases in vivo. We conclude that mechanisms other than inhibition of HLCS cause body fat loss in flies. We propose that the primary candidate is the inhibition of the insulin receptor/Akt signaling pathway.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
4-Hydroxybenzoic acid, ReagentPlus®, ≥99%
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2-Hydroxybutyric acid sodium salt, 97%
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3-Hydroxybenzoic acid, ReagentPlus®, 99%
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4-Hydroxybenzoic acid, ReagentPlus®, 99%
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trans-Ferulic acid, ≥99%
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4-Hydroxybenzoic acid, ≥99%, FG
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Fumaric acid, FCC, FG
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Citric acid, BioUltra, anhydrous, ≥99.5% (T)
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Citric acid, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.5%
SAFC
Fumaric acid
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