Search

Seasonal rhythms drive metabolic adaptations that influence body weight and adiposity. Adipose tissue is a key regulator of energy homeostasis in the organism, and its healthiness is needed to prevent the major consequences of overweight and obesity. In this context, supplementation with proanthocyanidins has been postulated as a potential strategy to prevent the alterations caused by obesity. Moreover, the effects of these (poly)phenols on metabolism are photoperiod dependent. In order to describe the impact of grape-seed proanthocyanidins extract (GSPE) on important markers of adipose tissue functionality under an obesogenic environment, we exposed Fischer 344 rats to three different photoperiods and fed them a cafeteria diet for five weeks. Afterwards, we supplemented them with 25 mg GSPE/kg/day for four weeks. Our results revealed that GSPE supplementation prevented excessive body weight gain under a long photoperiod, which could be explained by increased lipolysis in the adipose tissue. Moreover, cholesterol and non-esterified fatty acids (NEFAs) serum concentrations were restored by GSPE under standard photoperiod. GSPE consumption slightly helped combat the obesity-induced hypertrophy in adipocytes, and adiponectin mRNA levels were upregulated under all photoperiods. Overall, the administration of GSPE helped reduce the impact of obesity in the adipose tissue, depending on the photoperiod at which GSPE was consumed and on the type of adipose depots.

Hypertension (HTN) is one of the leading causes of death in the world. Agri-food by-products are emerging as a novel source of natural antihypertensive agents allowing for their valorization and making food and agricultural industries more environmentally friendly. In this regard, wine making process generates large amounts of by-products rich in phenolic compounds that have shown potential to exert several beneficial effects including antihypertensive properties. The aim of this study was to review the blood pressure-lowering effects of winery by-products. In addition, molecular mechanisms involved in their bioactivity were also evaluated. Among the winery by-products, grape seed extracts have widely shown antihypertensive properties in both animal and human studies. Moreover, recent evidence suggests that grape stem, skin and pomace and wine lees may also have great potential to manage HTN, although more studies are needed in order to confirm their potential in humans. Improvement of endothelial dysfunction and reduction of oxidative stress associated with HTN are the main mechanisms involved in the blood pressure-lowering effects of these by-products.

A plant’s stress response involves the production of phytochemicals, including phenolic compounds. Their synthesis can be modulated by organic (ORG) or non-organic (NORG) farming systems in which they are grown. To examine this issue, thirteen plant-based foods cultivated in ORG and NORG systems were compared in terms of antioxidant capacity, total content of phenolics, anthocyanins, flavan-3-ols and flavonols. The results showed that NORG fruits tended to have higher phenolic compounds content, whereas ORG fruits had more antioxidant capacity. NORG legume stood out for having higher values from all the parameters analyzed in comparison to its ORG equivalent. ORG nuts showed more flavan-3-ols and flavonols than their NORG counterparts, nonetheless, tended to be less antioxidant. ORG vegetables displayed higher phenolics and anthocyanins, which reflected in higher antioxidant capacity than NORG ones. These findings suggest that farming systems differentially modulate phenolic compound composition and antioxidant capacity based on the plant species studied.

Background Phenolic compounds are one of the most heterogeneous group of plant secondary metabolites with over 50,000 diverse molecules identified so far. Despite the low bioavailability of native forms, they have been shown to exert several beneficial effects against chronic diseases such as diabetes, cardiovascular disease, and neurodegenerative diseases. There are different factors that may affect their absorption and distribution in tissues, but the exact mechanisms remain unclear. Recently, the time of the day and the season of the year in which they are consumed have emerged as another factor that may significantly impact on their metabolism and bioactivities. Scope and approach This review emphasizes the importance of the interaction between phenolic compounds and biological rhythms and its impact on the bioactivities of these metabolites. This may have implications for the food industry as food rich in phenolic compounds may exert different effects depending on the time of consumption. Key findings and conclusions Phenolic compounds broad activity could be explained by their extensive transformation, including metabolization in the colon by the gut microbiota, which leads to the production of multitude of different metabolites. Biological rhythms play a significant role in this metabolism affecting their bioactivities and, at the same time, phenolic compounds may exert their effects by promoting homeostasis at a basal signalling level through interactions with the biological clock system. This is in accordance with the xenohormesis hypothesis, which explains that chemical cues synthetized by plants are able to allow animals to favourably adapt to changing environmental conditions.

Do you think that eating fruit in summer has the same effect on your body as does eating it in winter? Scientific evidence says no. Fruits contain polyphenols, which are substances produced by plants in response to the growing conditions. When animals eat these fruits, polyphenols signal animals’ bodies to adapt to the seasons. For example, bears eat berries in late summer because these fruits provide essential substances needed during hibernation. It has been observed that the effect of these fruit substances is affected by biological rhythms, which are chemical cycles that animals’ bodies follow that vary throughout the year. Thus, eating fruit in- or out-of-season generates different effects in your body. Eating fruit in-season is associated with optimal health effects. Hence, we must eat fruits in-season so that the rhythms of our lives are synchronized with the seasons.

Tomatoes (Lycopersicon esculentum Mill.) constitute an important source of health-promoting compounds including bioactive antioxidants, such as flavonoids, that can differ in terms of composition and quantity depending on the conditions that tomatoes are cultivated. Otherwise, biological rhythms modulate oxidative stress. Therefore, the aim of this study was to evaluate the antioxidant properties of seasonally consumed tomatoes from two different geographical origins (local LT or non-local NLT) in Fischer 344 rats. The results show that LT and NLT have a specific phenolic signature and that each tomato gives a particular response toward biomarkers evaluated, which in turn showed a photoperiod-dependent effect. Remarkably, when tomatoes were administered in-season they improved or sustained antioxidant biomarkers, thus reducing oxidative stress values. It is noteworthy that the protective effect of tomatoes against oxidative stress depends on the geographical origin of the crop. Therefore, tomatoes consumed in-season may improve health by preventing oxidative stress.

Variations in the light/dark cycle and obesogenic diets trigger physiological and behavioral disorders. Proanthocyanidins, in addition to their healthy properties, have recently demonstrated a modulating effect on biological rhythms. Therefore, the aim of this study was to evaluate the administration of a grape seed proanthocyanidin-rich extract (GSPE) to mitigate the disruption caused by a sudden photoperiod change in healthy and cafeteria (CAF)-diet obese rats. For this, 48 photoperiod-sensitive Fischer 344 rats were fed standard or CAF diets for 6 weeks under a standard (12 h light/day, L12) conditions. Then, rats were switched to a long (18 h light/day, L18) or short (6 h light/day, L6) photoperiod and administered vehicle or GSPE (25 mg/kg) for 1 week. Body weight (BW) and food intake (FI) were recorded weekly. Animal activity and serum hormone concentrations were studied before and after the photoperiod change. Hormone levels were measured both at 3 h (ZT3) and 15 h (ZT15) after the onset of light. Results showed the impact of the CAF diet and photoperiod on the BW, FI, activity, and hormonal status of the animals. GSPE administration resulted in an attenuation of the changes produced by the photoperiod disruption. Specifically, GSPE in L6 CAF-fed rats reduced serum corticosterone concentration, restoring its circadian rhythm, increased the T3-to-T4 ratio, and increased light phase activity, while under L18, it decreased BW and testosterone concentration and increased the animal activity. These results suggest that GSPE may contribute to the adaptation to the new photoperiods. However, further studies are needed to elucidate the metabolic pathways and processes involved in these events.

Cardiovascular diseases (CVD) are the leading cause of deaths worldwide and their prevalence is continuously increasing. Available treatments may present several side effects and therefore the development of new safer therapeutics is of interest. Phenolic compounds have shown several cardioprotective properties helpful in reducing different CVD risk factors such as inflammation, elevated blood pressure, hyperlipidemia, or endothelial dysfunction. These factors are significantly influenced by biological rhythms which are in fact emerging as key modulators of important metabolic and physiological processes. Thus, increased events of CVD have been observed under circadian rhythm disruption or in winter versus other seasons. These rhythms can also affect the functionality of phenolic compounds. Indeed, different effects have been observed depending on the administration time or under different photoperiods. Therefore, in this review the focus will be on the potential of phenolic compounds as therapeutics to prevent CVD via biological rhythm modulation.

International audience; Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies.

Grape-seed proanthocyanidin extract (GSPE) improve white adipose tissue (WAT) expansion during diet-induced obesity. However, because adipose metabolism is synchronized by circadian rhythms, it is plausible to speculate that the bioactivity of dietary proanthocyanidins could be influenced by the time-of-day in which they are consumed. Therefore, the aim of the present study was to determine the interaction between zeitgeber time (ZT) and GSPE consumption on the functionality of WAT in rats with diet-induced obesity.Male Wistar rats were fed a cafeteria diet for 9 weeks. After 5 weeks, the animals were supplemented with 25 mg GSPE/kg for 4 weeks at the beginning of the light/rest phase (ZT0) or of the dark/active phase (ZT12). Body fat content was determined by nuclear magnetic resonance and histological analyses were performed in the epididymal (EWAT) and inguinal (IWAT) fat depots to determine adipocyte size and number. In addition, the expression of genes related to adipose metabolism and circadian clock function were analyzed by qPCR.GSPE consumption at ZT0 was associated with a potential antidiabetic effect without affecting adiposity and energy intake and downregulating the gene expression of inflammatory markers in EWAT. In contrast, GSPE consumption at ZT12 improved adipose tissue expansion decreasing adipocyte size in IWAT. In accordance with this adipogenic activity, the expression of genes involved in fatty acid metabolism were downregulated at ZT12 in IWAT. In turn, GSPE consumption at ZT12, but not at ZT0, repressed the expression of the clock gene Cry1 in IWAT.The interaction between ZT and GSPE consumption influenced the metabolic response of WAT in a tissue-specific manner. Understanding the impact of circadian clock on adipose metabolism and how this is regulated by polyphenols will provide new insights for the management of obesity.

Circadian rhythm is an endogenous and self-sustained timing system, responsible for the coordination of daily processes in 24-h timescale. It is regulated by an endogenous molecular clock, which is sensitive to external cues as light and food. This study has previously shown that grape seed proanthocyanidins extract (GSPE) regulates the hepatic molecular clock. Moreover, GSPE is known to interact with some microRNAs (miRNAs). Therefore, the aim of this study is to evaluate if the activity of GSPE as modulator of hepatic clock genes can be mediated by miRNAs.250 mg kgmiRNA regulation of peripheral clocks via GSPE may be part of a complex mechanism that involves the crosstalk with the central system rather than a direct effect.

International audience; Cardiovascular and metabolic disorders present major causes of mortality in the ageing population. Polyphenols present in human diets possess cardiometabolic protective properties, however their underlying molecular mechanisms in humans are still not well identified. Even though preclinical and in vitro studies advocate that these bioactives can modulate gene expression, most studies were performed using targeted approaches. With the objective to decipher the molecular mechanisms underlying polyphenols cardiometabolic preventive properties in humans, we performed integrative multi-omic bioinformatic analyses of published studies which reported improvements of cardiometabolic risk factors following polyphenol intake, together with genomic analyses performed using untargeted approach. We identified 5 studies within our criteria and nearly 5000 differentially expressed genes, both mRNAs and miRNAs, in peripheral blood cells. Integrative bioinformatic analyses (e.g. pathway and gene network analyses, identification of transcription factors, correlation of gene expression profiles with those associated with diseases and drug intake) revealed that these genes are involved in the processes such as cell adhesion and mobility, immune system, metabolism, or cell signaling. We also identified 27 miRNAs known to regulate processes such as cell cytoskeleton, chemotaxis, cell signaling, or cell metabolism. Gene expression profiles negatively correlated with expression profiles of cardiovascular disease patients, while a positive correlation was observed with gene expression profiles following intake of drugs against cardiometabolic disorders. These analyses further advocate for health protective effects of these bioactives against age-associated diseases. In conclusion, polyphenols can exert multigenomic modifications in humans and use of untargeted methods coupled with bioinformatic analyses represent the best approach to decipher molecular mechanisms underlying healthy-ageing effects of these bioactives.

The antihypertensive effect of wine lees powder (WLPW) from a Cabernet grape variety was related to its high content in flavanols and anthocyanins compounds. This study investigates the involvement of endothelial-derived factors and SIRT1 in its bioactivity. Spontaneously hypertensive rats (SHR) were orally administered water or WLPW (125 mg/kg bw). Posteriorly, both groups were intraperitoneally administered saline, Nω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthesis inhibitor, indomethacin, a prostacyclin synthesis inhibitor, or sirtinol, an inhibitor of sirtuins. Blood pressure (BP) was recorded before and 6 h after WLPW administration. In an additional experiment, SHR were administered water or WLPW and endothelial expressions of eNos, Sirt1, Nox4, and Et1 were determined. The BP-lowering properties of WLPW were abolished by L-NAME and partially reduced by indomethacin, demonstrating that WLPW antihypertensive effect was mediated by changes in NO availability, although prostacyclin also contributed to this activity. Moreover, BP-lowering effect was reduced by sirtinol, indicating that WLPW decreased BP in a SIRT1-dependent manner. Furthermore, WLPW upregulated eNos and Sirt1 and downregulated Nox4 and Et1 endothelial gene expression. These results evidence the vasoprotective effect of WLPW and show that its antihypertensive effect in SHR is endothelium dependent and mediated by SIRT1.

The aim of this study was to evaluate the effect of long-term administration of the protein hydrolysate from chicken feet Hpp11 in diet-induced hypertensive rats. Rats were fed standard or cafeteria (CAF) diets for 12 weeks, and during the final 3 weeks, CAF animals were administered vehicle, Captopril or Hpp11. Systolic blood pressure (SBP) was recorded weekly. Body weight and plasmatic lipid and glucose levels were determined. Moreover, liver-reduced glutathione (GSH) levels, plasmatic angiotensin converting enzyme (ACE) activity and the endothelial gene expression of eNOS, KLF-2, Sirt-1, NOX4 and ET-1 were studied. A definite decrease in SBP was recorded in the rats that were administered Hpp11. Hpp11 downregulated gene expression of the vasoconstrictor ET-1 and induced the upregulation of NOX4 and NO enhancer Sirt-1, suggesting the vasoprotective effect of Hpp11. Moreover, Hp11 increased hepatic GSH. The present findings suggest that Hpp11 is a good candidate to ameliorate diet-induced hypertension.

Enzymatic-assisted extraction using Flavourzyme® has been demonstrated to be a useful methodology to obtain wine lees (WL) enriched in phenolic compounds and with enhanced antihypertensive activity. Nevertheless, taking into account that Flavourzyme® possess proteolytic activity, the release of bioactive peptides should not be ruled out. In this study, we investigate the presence of antihypertensive peptides in the WL hydrolysate. Peptides were separated into fractions by ultrafiltration and RP‐HPLC. Next, peptide identification by nano-HPLC-(Orbitrap)MS/MS was performed in the fractions showing the highest angiotensin-converting enzyme inhibitory (ACEi) activities. Six peptides were identified; three of them showing ACEi (IC50) values lower than 20 µM. The peptide antihypertensive effect was evaluated in spontaneously hypertensive rats at an oral dose of 10 mg/kg bw. Peptides FKTTDQQTRTTVA, NPKLVTIV, TVTNPARIA, LDSPSEGRAPG and LDSPSEGRAPGAD exhibited antihypertensive activity, confirming that they could contribute to the blood pressure-lowering effect of the WL hydrolysate. These peptides have a great potential as functional ingredients to manage hypertension.

The antihypertensive effect of the soluble fraction of wine lees (WL) from Cabernet variety grapes was recently reported by our group. This blood pressure (BP)-lowering effect was attributed to the presence of flavanols and anthocyanins. In this context, phenolic-enriched wine lees (PWL) could potentially exhibit a stronger bioactivity. Therefore, the aim of this study was to obtain a soluble fraction of WL with increased phenolic content and evaluate its functionality. The PWL were obtained using an enzyme-assisted extraction based on the hydrolysis of WL proteins with Flavourzyme®. They contained 57.20% more total phenolic compounds than WL, with anthocyanins and flavanols being the largest families present. In addition, PWL also showed greater angiotensin-converting enzyme inhibitory and antioxidant activities. Finally, the antihypertensive activity of the PWL was evaluated in spontaneously hypertensive rats. A single dose of 5 mL/kg body weight of PWL showed a greater BP-lowering effect than the one shown by WL. Moreover, this antihypertensive effect was more prolonged than the one produced by the antihypertensive drug Captopril. These results demonstrate that enzymatic protein hydrolysis is a useful method to maximize the extraction of phenolic compounds from WL and to obtain extracts with enhanced functionalities.

The antihypertensive effect of wine lees (WL) has been previously evidenced. In this study, the antihypertensive properties of different doses of WL were evaluated in spontaneously hypertensive rats (SHR). In addition, the blood pressure (BP)-lowering effect of dried (dealcoholized) WL powder (WLPW) and the mechanisms involved in its functionality were investigated. Furthermore, a possible hypotensive effect of WLPW was discarded in Wistar–Kyoto (WKY) rats. The administration of WL at different doses caused a dose-dependent decrease in BP of SHR up to 5.0 mL/kg bw, exhibiting the maximum decrease at 6 h post-administration. WLPW caused a greater drop in BP than WL, showing an antihypertensive effect higher and more prolonged than the drug Captopril. Moreover, the BP-lowering effect of WLPW was specific to the hypertensive state since an undesirable hypotensive effect in normotensive WKY rats was ruled out. Finally, WLPW improved oxidative stress and increased the activity of the antioxidant endogen system of SHR. These results suggest that WLPW could be used as functional ingredient for foods or nutraceuticals to ameliorate hypertension. Nevertheless, further clinical studies are needed to evaluate its long-term antihypertensive efficiency.

Wine lees (WL) are by-products generated in the winemaking process. The aim of this study was to investigate the angiotensin-converting enzyme inhibitory (ACEi) activity, and the blood pressure (BP) lowering effect of WL from individual grape varieties. The relationship among their activities and phenolic profiles was also studied. Three WL, from Cabernet, Mazuela, and Garnacha grape varieties, were firstly selected based on their ACEi properties. Their phenolic profiles were fully characterized by UHPLC-ESI-Q-TOF-MS. Then, their potential antihypertensive effects were evaluated in spontaneously hypertensive rats (SHR). BP was recorded before and after their oral administrations (2, 4, 6, 8, 24, and 48 h) at a dose of 5 mL/kg bw. Cabernet WL (CWL) exhibited a potent antihypertensive activity, similar to that obtained with the drug Captopril. This BP-lowering effect was related to the high amount of anthocyanins and flavanols present in these lees. In addition, a potential hypotensive effect of CWL was discarded in normotensive Wistar–Kyoto rats. Finally, the ACEi and antihypertensive activities of CWL coming from a different harvest were confirmed. Our results suggest the potential of CWL for controlling arterial BP, opening the door to commercial use within the wine industry.

The body weight-lowering properties of a multifunctional ingredient (MIX) based on conjugated linoleic acid at low doses, the flavonoids proanthocyanidins and anthocyanidins and the chicken feet hydrolysate Hpp11 have been previously reported. The aim of this study was to evaluate the effect of long-term administration of MIX on other cardiometabolic risk factors associated with metabolic syndrome (MetS) in rats fed a cafeteria diet (CAF). Male Wistar rats were fed CAF for 11 weeks, and during the last 3 weeks, animals were orally administered MIX or vehicle. Lipid tolerance tests were performed before and after MIX administration. At the end of the experimental period, serum and inguinal white adipose tissue (iWAT) metabolism were analyzed by metabolomics and biochemical approaches. The metabolite signature of serum and iWAT significantly changed after 3 weeks of MIX administration, suggesting an improvement in lipid and glucose homeostasis in these animals. In addition, MIX also exhibited significant antihypertensive properties. These results suggest that MIX could be a good candidate to ameliorate the cardiometabolic risk factors related to MetS.

The development of hypertension (HTN) in cafeteria (CAF) diet-fed rats was demonstrated to be attenuated after grape seed proanthocyanidin extract (GSPE) administration. However, the long-term antihypertensive effect of GSPE in animals with established HTN has not been investigated. Thus, the aim of this study was to evaluate if GSPE shows a blood pressure-lowering effect in hypertensive rats after its administration for 3 weeks. Wistar rats were fed a standard or CAF diet for 12 weeks, and during the last 3 weeks, animals were administered vehicle, captopril or a low dose of GSPE (25 mg per kg body weight, bw). Both systolic and diastolic blood pressure (SBP and DBP) were monitored weekly. The liver reduced glutathione (GSH) levels, plasma angiotensin converting enzyme activity and endothelial gene expression of eNOS, KLF-2, Sirt-1, NOX4 and ET-1 were studied at the end-point. The results demonstrated that 3 weeks of CAF diet administration with 25 mg per kg bw GSPE significantly reduced SBP and DBP in hypertensive rats. GSPE induced the upregulation of Sirt-1 gene expression and downregulated the vasoconstrictor ET-1, suggesting the vasoprotective effect of GSPE and increased the antioxidant GSH activity. The administration of 25 mg per kg bw GSPE for 3 weeks significantly reduced BP in CAF diet fed animals with established HTN.

Background & aims: The peptide and protein composition of olive oil is mostly unknown and the few studies available have not focused on the study of its low molecular weight peptides. We hypothesised that olive oil could naturally contain low molecular weight peptides with antihypertensive effect. Methods: We produced virgin olive oil (unfiltered, var. Picual) and obtained a water-soluble peptide extract. We fractionated the peptide extract by FPLC and studied its angiotensin converting enzyme (ACE) inhibitory activity. We studied the antihypertensive effect of olive oil peptides on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) using an animal model of hypertension (spontaneously hypertensive rats, SHR). The animals were randomly distributed into 3 study groups (n = 8 per group) and received an oral dose of olive oil peptides (0.425 mg/kg of BW), or a dose of Captopril (50 mg/kg of BW) or water. SBP and DBP were registered in the rats before administration and a at 2, 4, 6, 8, 24 and 48 h post-administration of the corresponding dose. Results: The peptide extract and FPLC purified fractions possessed angiotensin converting enzyme (ACE) inhibitory activity. Acute oral administration of olive oil water-soluble extract produced an average blood pressure reduction of 10 mmHg at 4 h (P < 0.01) and reached a maximum antihypertensive effect of 20 mmHg at 6 h, compared with baseline. Conclusion: Unfiltered virgin olive oil contains peptides and a water-soluble extract obtained from this oil possesses ACE inhibitory activity and in vivo antihypertensive effect., This project has been supported by European Regional Development Funds under the agreement signed between MINECO and CSIC for the realization of the RECUPERA 2020 project. Competing financial interests: the authors declare that they have no conflict of interest with the contents of this article.

Flavanol intake positively influences several cardiometabolic risk factors in humans. However, the specific molecular mechanisms of action of flavanols, in terms of gene regulation, in the cell types relevant to cardiometabolic disease have never been systematically addressed. On this basis, we conducted a systematic literature review and a comprehensive bioinformatic analysis of genes whose expression is affected by flavanols in cells defining cardiometabolic health: hepatocytes, adipocytes, endothelial cells, smooth muscle cells and immune cells. A systematic literature search was performed using the following pre-defined criteria: treatment with pure compounds and metabolites (no extracts) at low concentrations that are close to their plasma concentrations. Differentially expressed genes were analyzed using bioinformatics tools to identify gene ontologies, networks, cellular pathways and interactions, as well as transcriptional and post-transcriptional regulators. The systematic literature search identified 54 differentially expressed genes at the mRNA level in in vitro models of cardiometabolic disease exposed to flavanols and their metabolites. Global bioinformatic analysis revealed that these genes are predominantly involved in inflammation, leukocyte adhesion and transendothelial migration, and lipid metabolism. We observed that, although the investigated cells responded differentially to flavanol exposure, the involvement of anti-inflammatory responses is a common mechanism of flavanol action. We also identified potential transcriptional regulators of gene expression: transcriptional factors, such as GATA2, NFKB1, FOXC1 or PPARG, and post-transcriptional regulators: miRNAs, such as mir-335-5p, let-7b-5p, mir-26b-5p or mir-16-5p. In parallel, we analyzed the nutrigenomic effects of flavanols in intestinal cells and demonstrated their predominant involvement in the metabolism of circulating lipoproteins. In conclusion, the results of this systematic analysis of the nutrigenomic effects of flavanols provide a more comprehensive picture of their molecular mechanisms of action and will support the future setup of genetic studies to pave the way for individualized dietary recommendations., COST (European Cooperation in Science and Technology) Action FA1403.

To correlate the beneficial effects of cherry consumption with their phenolic composition, a full and precise characterization is required. However, there is not a specific method to fully extract all phenolic compounds from sweet cherries. Thus, this study aimed to optimize the extraction of sweet cherry phenolics by response surface methodology and fully characterize the phenolic profile of Royal Dawn sweet cherries by HPLC-ESI-MS/MS. Extraction conditions were evaluated and optimized to 55 °C, MeOH 72%, 12 mL/g in two extraction steps. Royal Dawn sweet cherries presented rutin as the predominant phenolic compound, unlike most sweet cherry varieties. Additionally, ethanol was evaluated as a replacement solvent, obtaining lower extraction rates, especially for anthocyanins. However, in terms of total amounts, non-anthocyanin compounds were similarly extracted. The developed methodology was fast and can be routinely used in the evaluation of the phenolic profile of sweet cherries and to produce phenolic-rich extracts for the food industry.

Scope Phenolic compounds are bioactive molecules that are associated with several health benefits. Metabolization and absorption are the main determinants of their bioavailability and bioactivity. Thus, the study of the factors that modulate these processes, such as sex or diet is essential. Recently, it has been shown that biological rhythms may also play a key role. Hence, the aim of this study was to evaluate if the bioavailability of a grape proanthocyanidin extract (GSPE) is affected by the administration time in an animal model of metabolic syndrome (MetS). Methods and results Female and male Fischer 344 rats were fed either a standard or a cafeteria diet (CAF) for 9 weeks, and an oral dose of GSPE (25 mg/kg) was daily administered either at 8:00 am (ZT-0) or at 8:00 pm (ZT-12) during the last 4 weeks. Plasma phenolic compounds were then quantified by HPLC-ESI-MS / MS. Phase-II and gut microbiota-derived phenolic metabolites were affected by ZT in all conditions or only in obese rats, respectively. CAF feeding affected the bioavailability of phenolic acids and free flavan-3-ols. Differences due to sex were also observed. Conclusion These findings demonstrate that ZT, diet and sex are key factors influencing phenolic compounds bioavailability. This article is protected by copyright. All rights reserved.

Objectives: White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with insulin resistance and dyslipidemia independently of body composition and fat distribution. In contrast, hyperplasia protects against metabolic alterations. Proanthocyanidins, which are the most abundant flavonoids in the human diet, improve metabolic disturbances associated with diet-induced obesity without reducing body weight or adiposity. The aim of this study was to determine whether grape seed proanthocyanidin extract (GSPE) can modulate WAT expandability. Because GSPE also contains gallic acid, we also studied the capacity of gallic acid to remodel WAT. Design: Male Wistar rats were fed a standard chow diet (n=6) or a cafeteria diet (CAF) for 11 weeks. After 8 weeks, the CAF-fed animals were supplemented with 25 mg GSPE/kg body weight (n=6), 7 mg gallic acid/kg body weight (n=6) or the vehicle (n=6) for 3 weeks. Histological analyses were performed in the retroperitoneal (rWAT) and inguinal (iWAT) WAT to determine adipocyte size and number. Specific markers for adipogenesis and WAT functionality were analysed in rWAT using quantitative RT-PCR. Results: GSPE or gallic acid supplementation did not reduce weight gain or reverse and adiposity. However, GSPE reduced adipocyte size significantly in rWAT and moderately in iWAT and tripled the adipocyte number in rWAT. Gallic acid slightly reduced adipocyte size in rWAT and iWAT and doubled the adipocyte number in both WATs. In accordance with this adipogenic activity, Pref-1 and PPARγ tended to be overexpressed in rWAT of rats supplemented with GSPE. Moreover, GSPE supplementation increased Plin1 and Fabp4 expression and restored adiponectin expression completely, indicating a better functionality of visceral WAT. Conclusions: GSPE supplementation has anti-hypertrophic and hyperplasic activities in rats with established obesity, mainly in visceral WAT inducing a healthier expansion of WAT to match the surplus energy provided by the cafeteria diet.

Biological rhythms can influence the activity of bioactive compounds, and at the same time, the intake of these compounds can modulate biological rhythms. In this context, chrononutrition has appeared as a research field centered on the study of the interactions among biological rhythms, nutrition, and metabolism. This review summarizes the role of phenolic compounds in the modulation of biological rhythms, focusing on their effects in the treatment or prevention of chronic diseases. Heterotrophs are able to sense chemical cues mediated by phytochemicals such as phenolic compounds, promoting their adaptation to environmental conditions. This is called xenohormesis. Hence, the consumption of fruits and vegetables rich in phenolic compounds exerts several health benefits, mainly attributed to the product of their metabolism. However, the profile of phenolic compounds present in plants differs among species and is highly variable depending on agricultural and technological factors. In this sense, the seasonal consumption of polyphenol-rich fruits could induce important changes in the regulation of physiology and metabolism due to the particular phenolic profile that the fruits contain. This fact highlights the need for studies that evaluate the impact of these specific phenolic profiles on health to establish more accurate dietary recommendations. España MINISTERIO DE ECONOMÍA, INDUSTRIA Y COMPETITIVIDAD (AGL2016-77105-R)

Fruits are rich in phenolic compounds with health-promoting activities. However, phenolic profiles vary between fruits. Hence, specific extraction methods are required for accurate profiling of the functional compounds. This study aims to develop an optimised method by response surface methodology to extract phenolics from apricots (Prunus armeniaca) and correctly characterise apricots' phenolic profile. For this, the effects of the solid-to-liquid ratio, temperature, extraction solvent, extraction time and sequential extraction steps on the extraction of major phenolic families were investigated. Methanol- and ethanol-based extractions were suitable, although methanol was the optimal solvent. The optimised extraction conditions were 20 g mL-1, 38 °C and 72% methanol (1% formic acid). When this method was used in apricots, the characterisation of their phenolic profile by HPLC-ESI-MS/MS showed a higher extraction of phenolic compounds than other studies in the literature that use non-specific extraction methods. The developed method is fast and economically feasible for accurate characterisation of the phenolic profile of apricot fruits and thus can be routinely used to extract apricot phenolic compounds for their characterisation.