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Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity

ABSTRACT: An expression profiling was conducted to analyse the effect of the bitter tasting compounds denatonium benzoate (DB) or aloin on the transcriptome of human jejunal crypts compared to DMEM-treated crypts. These two bitter compounds are agonists for the human bitter taste receptor TAS2R43. We took advantage of a deletion polymorphism for TAS2R43, that exists in about 33% of the population to compare the effects of the TAS2R43 agonists in obese subjects that express (TAS2R43(+)) or do not express (TAS2R43(-)) TAS2R43. Primary jejunal crypts from lean (multi-organ donors) or obese (RYGB surgery) subjects were cultured for 24 hours and treated for 4 hours with either DMEM (control) or 1 mM DB or 30 µM aloin. In total 48 mRNA samples were subjected to RNAseq analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186509 | GEO | 2021/11/23

REPOSITORIES: GEO

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Project description:INTRODUCTION: Bitter melon (Momordica charantia, Cucurbitaceae) is a popular edible medicinal plant, which has been used as a botanical dietary supplement for the treatment of diabetes and obesity in Chinese folk medicine. Previously, our team has proved that cucurbitanes triterpenoid were involved in bitter melon's anti-diabetic effects as well as on increasing energy expenditure. The triterpenoids composition can however be influenced by changes of varieties or habitats.OBJECTIVES: To clarify the significance of bioactive metabolites diversity among different bitter melons and to provide a guideline for selection of bitter melon varieties, an exploratory study was carried out using a UHPLC-HRMS based metabolomic study to identify chemotypes.METHODS: Metabolites of 55 seed samples of bitter melon collected in different parts of China were profiled by UHPLC-HRMS. The profiling data were analysed with multivariate (MVA) statistical methods. Principle component analysis (PCA) and hierarchical cluster analysis (HCA) were applied for sample differentiation. Marker compounds were identified by comparing spectroscopic data with isolated compounds, and additional triterpenes were putatively identified by propagating annotations through a molecular network (MN) generated from UHPLC-HRMS & MS/MS metabolite profiling.RESULTS: PCA and HCA provided a good discrimination between bitter melon samples from various origins in China. This study revealed for the first time the existence of two chemotypes of bitter melon. Marker compounds of those two chemotypes were identified at different MSI levels. The combined results of MN and MVA demonstrated that the two chemotypes mainly differ in their richness in cucurbitane versus oleanane triterpenoid glycosides (CTGs vs. OTGs).CONCLUSION: Our finding revealed a clear chemotype distribution of bioactive components across bitter melon varieties. While bioactivities of individual CTGs and OTGs still need to be investigated in more depth, our results could help in future the selection of bitter melon varieties with optimised metabolites profile for an improved management of diabetes with this popular edible Chinese folk medicine.

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Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity

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