Olive oil phenolic constituents have been shown, in vitro, to be endowed with potent biological activities including, but not limited to, an antioxidant action. To date, there is no information on the absorption and disposition of such compounds in humans. We report that olive oil phenolics, namely tyrosol and hydroxytyrosol, are dose-dependently absorbed in humans after ingestion and that they are excreted in the urine as glucuronide conjugates. Furthermore, an increase in the dose of phenolics administered increased the proportion of conjugation with glucuronide.z 2000 Federation of European Biochemical Societies.

EVOO consumption by mildly dyslipidemic patients is associated with favorable changes in circulating markers of cardiovascular condition. Based on current knowledge, these effects may be associated with cardioprotection.

Bile acid metabolism plays an essential role in cholesterol homeostasis and is critical for the initiation of atherosclerotic disease. However, despite the recent advances, the molecular mechanisms whereby bile acids regulate gene transcription and cholesterol homeostasis in mammals still need further investigations. Here, we show that bile acids suppress transcription of the gene (CYP7A1) encoding cholesterol 7␣-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, also through an unusual mechanism not involving the bile acid nuclear receptor, farnesoid X receptor. By performing cell-based reporter assays, protein/protein interaction, and chromatin immunoprecipitation assays, we demonstrate that bile acids impair the recruitment of peroxisome proliferator-activated receptor-␥ coactivator-1␣ and cAMP response element-binding protein-binding protein by hepatocyte nuclear factor-4␣, a master regulator of CYP7A1. We also show for the first time that bile acids inhibit transcription of the gene (PEPCK) encoding phosphoenolpyruvate carboxykinase, the rate-limiting enzyme in gluconeogenesis, through the same farnesoid X receptor-independent mechanism. Chromatin immunoprecipitation assay revealed that bile acid-induced dissociation of coactivators from hepatocyte nuclear factor-4␣ decreased the recruitment of RNA polymerase II to the core promoter and downstream in the 3-untranslated regions of these two genes, reflecting the reduction of gene transcription. Finally, we found that Cyp7a1 expression was stimulated in fasted mice in parallel to Pepck, whereas the same genes were repressed by bile acids. Collectively, these results reveal a novel regulatory mechanism that controls gene transcription in response to extracellular stimuli and argue that the transcription regulation by bile acids of genes central to cholesterol and glucose metabolism should be viewed dynamically in the context of the fasted-to-fed cycle.

Bile acids regulate the cholesterol 7␣-hydroxylase gene (CYP7A1), which encodes the rate-limiting enzyme in the classical pathway of bile acid synthesis. Here we report a novel mechanism whereby bile acid feedback regulates CYP7A1 transcription through the nuclear receptor hepatocyte nuclear factor-4 (HNF-4), which binds to the bile acid response element (BARE) at nt ؊149/ ؊118 relative to the transcription start site.

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Interest in the in vivo biological activities of olive oil phenolics is rapidly growing, and different models and vehicles of administration are used worldwide. Matters of practicality determine the use of rats rather than humans as the model of choice. Also, growing interest in nutraceuticals is leading to the formulation of compounds containing olive oil phenols. In this study, we compared metabolism and urinary excretion of hydroxytyrosol [(HT), the most representative phenol of olive oil] between rats and humans by evaluating excretion of HT and its major metabolite, homovanillyl alcohol. Also, we compared human excretion of HT when consumed as a natural component of extra virgin olive oil, when added to refined olive oil, or when added to yogurt (as an approximation of functional food). Urinary excretion of HT was greater in humans than in rats, a species with a high basal excretion of HT and its metabolites. The high (234% of HT administered) excretion of free HT suggests that hydrolysis of oleuropein administered in humans (still an unresolved issue) occurs in vivo. Moreover, human HT excretion was much higher after its administration as a natural component of olive oil (44.2% of HT administered) than after its addition to refined olive oil (23% of HT administered) or yogurt (5.8% of dose or approximately 13% of that recorded after virgin olive oil intake). These data suggest that the rat is not the appropriate model for the study of HT metabolism and that HT-containing functional foods should be carefully formulated.

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Envirotyping is an essential technique used to unfold the non-genetic drivers associated with the phenotypic adaptation of living organisms. Here we introduce the EnvRtype R package, a novel toolkit developed to interplay large-scale envirotyping data (enviromics) into quantitative genomics. To start a user-friendly envirotyping pipeline, this package offers: (1) remote sensing tools for collecting (get_weather and extract_GIS functions) and processing ecophysiological variables (processWTH function) from raw environmental data at single locations or worldwide; (2) environmental characterization by typing environments and profiling descriptors of environmental quality (env_typing function), in addition to gathering environmental covariables as quantitative descriptors for predictive purposes (W_matrix function); and (3) identification of environmental similarity that can be used as an enviromic-based kernel (env_typing function) in whole-genome prediction (GP), aimed at increasing ecophysiological knowledge in genomic best-unbiased predictions (GBLUP) and emulating reaction norm effects (get_kernel and kernel_model functions). We highlight literature mining concepts in fine-tuning envirotyping parameters for each plant species and target growing environments. We show that envirotyping for predictive breeding collects raw data and processes it in an eco-physiologically-smart way. Examples of its use for creating global-scale envirotyping networks and integrating reaction-norm modeling in GP are also outlined. We conclude that EnvRtype provides a cost-effective envirotyping pipeline capable of providing high quality enviromic data for a diverse set of genomic-based studies, especially for increasing accuracy in GP across untested growing environments.