Background & Aims
It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca2+ signaling in fungiform taste bud cells (TBC).
Methods
We measured Ca2+ signaling in human TBC, transfected with small interfering RNAs (siRNAs) against mRNAs encoding CD36 and GPR120 (or control siRNAs). We also studied Ca2+ signaling in TBC from CD36−/− mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and GLP-1 from human and mice TBC in response to CD36 and GPR120 activation.
Results
High concentrations of linoleic acid induced Ca2+ signaling via CD36 and GPR120 in human and mice TBC as well as in STC-1 cells, whereas low concentrations induced Ca2+ signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid downregulated CD36 and upregulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca2+ and serotonin responses but increased release of GLP1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts.
Conclusions
CD36 and GPR120 have non-overlapping roles in TBC signaling during oro-gustatory perception of dietary lipids; these are differentially regulated by obesity.
Liverworts produce a great variety of lipophilic terpenoids, aromatic compounds, and acetogenins. Many of these constituents have characteristic scents, pungency, and bitterness, and display a quite extraordinary array of bioactivities and medicinal properties. These expressions of biological activity are summarized and discussed, and examples are given of the potential of certain lead compounds for structure-activity studies and synthesis.
Comparatively little attention has been paid to the bryophytes for use in the human diet or medicine in spite of the presence of 23 000 species globally. Several hundred new compounds have been isolated from the liverworts (Marchantiophyta), and more than 40 new carbon skeletons of terpenoids and aromatic compounds were found. Most of the liverworts studied elaborate characteristic odiferous, pungent, and bitter-tasting compounds, of which many show antimicrobial, antifungal, antiviral, allergic contact dermatitis, cytotoxic, insecticidal, anti-HIV, plant growth regulatory, neurotrophic, NO production and superoxide anion radical release inhibitory, muscle relaxing, antiobesity, piscicidal, and nematocidal activities. The biological effects ascribed to the liverworts are mainly due to lipophilic sesqui- and diterpenoids, phenolic compounds, and polyketides, which are the principal constituents of their oil bodies. Some mosses and liverworts produce significant levels of vitamin B and tocopherols, as well as prostaglandin-like highly unsaturated fatty acids. The most characteristic chemical phenomenon of the liverworts is that most of the sesqui- and diterpenoids are enantiomers of those found in higher plants. In this review, the chemical constituents and potential medicinal uses of bryophytes are discussed.
The Japanese marine sponge Discodermia calyx contains a major cytotoxic compound, calyculin A, which exhibits selective inhibition of protein phosphatases 1 and 2A. It has long been used as a chemical tool to evaluate intracellular signal transduction regulated by reversible protein phosphorylation. We describe the identification of the biosynthetic gene cluster of calyculin A by a metagenome mining approach. Single-cell analysis revealed that the gene cluster originates in the symbiont bacterium 'Candidatus Entotheonella' sp. A phosphotransferase encoded in the gene cluster deactivated calyculin A to produce a newly discovered diphosphate, which was actually the biosynthetic end product. The diphosphate had been previously overlooked because of the enzymatic dephosphorylation that occurred in response to sponge tissue disruption. Our work presents what is to our knowledge the first evidence for the biosynthetic process of calyculin A along with a notable phosphorylation-dephosphorylation mechanism to regulate toxicity, suggesting activated chemical defense in the most primitive of all multicellular animals.
Polyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding of gene cluster evolution provides a rationale for reprogramming of the biosynthetic machinery. Herein, we report characterization of giant modular polyketide synthases (PKSs) responsible for the production of aminopolyol polyketides. Heterologous expression of over 150 kbp polyketide gene clusters successfully afforded their products, whose stereochemistry was established by taking advantage of bioinformatic analysis. Furthermore, phylogenetic analysis of highly homologous but functionally diverse domains from the giant PKSs demonstrated the evolutionary mechanism for structural diversification of polyketides. The gene clusters characterized herein, together with their evolutionary insights, are promising genetic building blocks for de novo production of unnatural polyketides.
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