We have previously reported that procyanidins, a class of flavonoids, improve glycemia and exert an incretin-like effect, which was linked to their proven inhibitory effect on the dipeptidyl-peptidase 4 (DPP4) activity. However, their actual effect on incretin levels has not been reported yet. Therefore, in the present study we have evaluated whether a grape seed extract enriched in procyanidins (GSPE) modulates plasma incretin levels and attempted to determine the mechanisms involved. An acute GSPE treatment in healthy Wistar female rats prior to an oral glucose load induced an increase in plasma active glucagon-like peptide-1 (GLP-1), which was accompanied by an increase in the plasma insulin/glucose ratio and a simultaneous decrease in glucose levels. In agreement with our previous studies, the intestinal DPP4 activity was inhibited by the GSPE treatment. We have also assayed in vitro whether this inhibition occurs in inner intestinal tissues close to GLP-1-producing cells, such as the endothelium of the capillaries. We have found that the main compounds absorbed by intestinal CaCo-2 cells after an acute treatment with GSPE are catechin, epicatechin, B2 dimer and gallic acid, and that they inhibit the DPP4 activity in endothelial HUVEC cells in an additive way. Moreover, an increase in plasma total GLP-1 levels was found, suggesting an increase in GLP-1 secretion. In conclusion, our results show that GSPE improves glycemia through its action on GLP-1 secretion and on the inhibition of the inner intestinal DPP4 activity, leading to an increase in active GLP-1 levels, which, in turn, may affect the insulin release.

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. 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. 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. 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.

The consumption of sweet oranges has been linked to several health benefits, many of which are attributed to hesperidin, a flavanone that is present in high amounts in these fruits. However, other phenolic compounds can contribute to the bioactivity of sweet orange. To link those effects to their phenolic profile, the complete characterization of the phenolic profile is mandatory. Although many studies have profiled the phenolic composition of orange juices, their pulps, which retain phenolic compounds, are overlooked. This fact is particularly relevant because dietary guidelines recommend the consumption of whole fruits. Therefore, this study aimed to develop a specific method for the optimal extraction of phenolics from orange pulp and to use this method to characterize these fruits grown at different locations by HPLC-ESI-MS/MS. The extraction conditions that reported the highest total polyphenol content (TPC) and hesperidin contents were 20 mL/g, 55 °C, and 90% methanol. The extraction time and number of sequential steps were further evaluated and optimized as 20 min and two extraction steps, respectively. Although lower extraction rates were achieved when using ethanol as the extraction solvent, high TPC and hesperidin yields were obtained, suggesting the potential use of this methodology to produce phenolic-rich extracts for the food industry. By applying the optimized methodology and analyzing the extracts by HPLC-ESI-MS/MS, geographic cultivation regions were demonstrated to affect the phenolic profiles of oranges. In short, we developed a quick, easy-to-perform methodology that can be used to extract orange phenolics from pulp for their identification and quantification and to evaluate the factors that affect the phenolic profile in sweet orange pulps.

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.