Oxylipins (OXLs) are bioactive lipid metabolites derived from polyunsaturated fatty acids (PUFAs) which act as signaling molecules and are involved in inflammatory processes such as those that occur in obesity. On the other hand, gut microbiota plays an essential role in regulating inflammatory responses. However, little is known about the potential impact of gut bacteria on OXLs metabolism. Thus, the objective of this study was to investigate the effect of gut microbiota dysbiosis on plasma oxylipins profile in healthy and diet-induced obese animals. Eight-week-old male Wistar rats were fed with either a standard or cafeteria diet (CAF) for 5 weeks and administered an antibiotic cocktail (ABX) in the drinking water (Ampicillin: 1 g/ml, Vancomycin: 0.5 g/ml, Imipenem: 0.25 g/ml) for the last 2 weeks in order to induce gut microbiota dysbiosis. Metabolomics analysis of OXLs in plasma was performed by HPLC-MS analysis. No antibiotic treated animals were included as controls. Plasma OXLs profile was significantly altered due to both CAF feeding and ABX administration. ABX effect was more pronounced under obesogenic conditions. Several significant correlations between different bacteria taxa and these lipid mediators were observed. Among these, the positive correlation of Proteobacteria with LTB4, a proinflammatory OXL involved in obesity-related disorders, was especially remarkable. Gut microbiota plays a key role in regulating these lipid metabolites and, therefore, affecting oxylipins-mediated inflammatory processes. These results are the first evidence to our knowledge of gut microbiota impact on OXLs metabolism. Moreover, this can set the basis for developing new obesity markers based on OXLs and gut microbiota profiles.

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.

Major susceptibility to alterations in liver function (e.g., hepatic steatosis) in a prone environment due to circadian misalignments represents a common consequence of recent sociobiological behavior (i.e., food excess and sleep deprivation). Natural compounds and, more concisely, polyphenols have been shown as an interesting tool for fighting against metabolic syndrome and related consequences. Furthermore, mitochondria have been identified as an important target for mediation of the health effects of these compounds. Additionally, mitochondrial function and dynamics are strongly regulated in a circadian way. Thus, we wondered whether some of the beneficial effects of grape-seed procyanidin extract (GSPE) on metabolic syndrome could be mediated by a circadian modulation of mitochondrial homeostasis. For this purpose, rats were subjected to “standard”, “cafeteria” and “cafeteria diet + GSPE” treatments (n = 4/group) for 9 weeks (the last 4 weeks, GSPE/vehicle) of treatment, administering the extract/vehicle at diurnal or nocturnal times (ZT0 or ZT12). For circadian assessment, one hour after turning the light on (ZT1), animals were sacrificed every 6 h (ZT1, ZT7, ZT13 and ZT19). Interestingly, GSPE was able to restore the rhythm on clock hepatic genes (Bmal1, Per2, Cry1, Rorα), as this correction was more evident in nocturnal treatment. Additionally, during nocturnal treatment, an increase in hepatic fusion genes and a decrease in fission genes were observed. Regarding mitochondrial complex activity, there was a strong effect of cafeteria diet at nearly all ZTs, and GSPE was able to restore activity at discrete ZTs, mainly in the diurnal treatment (ZT0). Furthermore, a differential behavior was observed in tricarboxylic acid (TCA) metabolites between GSPE diurnal and nocturnal administration times. Therefore, GSPE may serve as a nutritional preventive strategy in the recovery of hepatic-related metabolic disease by modulating mitochondrial dynamics, which is concomitant to the restoration of the hepatic circadian machinery.

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.

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.