Verónica Arreaza-Gil

(Poly)phenols are plant-derived bioactive molecules that are associated with several health benefits. Therefore, it is essential to study the factors that affect the bioavailability of these phenolic compounds. Recently, circannual rhythms have been identified as one of the factors that may affect the bioavailability of these compounds. Hence, this study evaluates the impact of circannual rhythms on grape seed proanthocyanidins extract (GSPE) bioavailability in healthy and obesogenic contexts. Male Fischer 344 rats, fed standard (ST) or cafeteria (CAF) diets, were housed under different photoperiod conditions (6, 12, or 18 h of light per day) during 9 weeks and an oral dose of GSPE (25 mg/kg) was daily administered for the last 4 weeks. Serum GSPE-derived metabolites were then quantified by HPLC-ESI-MS/MS. A higher bioavailability was observed in rats exposed to a 12 h photoperiod and fed ST diet. However, this pattern was altered in CAF-fed rats, suggesting an attenuated influence of photoperiod under obesogenic conditions. These findings contribute to a better understanding of the complex relationships between diet, photoperiod, and serum metabolites.

Grape seed proanthocyanidins effects on metabolome are strongly influenced by sex and diet according to the time of administration.

Scope: Polyphenols health effects on obesity are mainly attributed to their metabolites generated after their gastrointestinal digestion, in which gut microbiota plays an important role. Moreover, gut microbiota composition and polyphenols bioavailability are influenced by differences in day light length (photoperiod). Thus, this study evaluates if a grape seed proanthocyanidins (GSPEs) extract bioavailability is influenced by different photoperiod exposure via gut microbiota modulation in an obesogenic context.Methods and results: Cafeteria diet‐induced obese Fischer 344 rats are housed under different photoperiod conditions (6, 12, or 18 h of light per day) during 9 weeks and administered with GSPE (25 mg kg⁻¹) or GSPE and an antibiotic cocktail (ABX) for the last 4 weeks. Serum GSPE‐derived metabolites are quantified by HPLC‐MS/MS.Conclusion: A higher bioavailability is observed under 6 h light/18 h darkness (L6) compared to 18 h light/6 h darkness (L18). Individual metabolites, especially those from the gut microbiota, are affected by photoperiods. ABX treatment alters these photoperiod‐mediated changes. Therefore, these results suggest that gut microbiota plays a key role in the photoperiod effects on GSPE bioavailability in obese rats.

Seasonal rhythms are emerging as a key factor influencing gut microbiota and bioactive compounds functionality as well as several physiological processes such as inflammation. In this regard, their impact on the modulation of oxylipins (OXLs), which are important lipid mediators of inflammatory processes, has not been investigated yet. Hence, we aimed to investigate the effects of photoperiods on OXLs metabolites in healthy and obesogenic conditions. Moreover, we evaluated if the impact of proanthocyanidins and gut microbiota on OXLs metabolism is influenced by photoperiod in obesity. To this purpose, Fischer 344 rats were housed under different photoperiod conditions (L6: 6 h light, L12: 12 h light or L18:18 h light) and fed either a standard chow diet (STD) or a cafeteria diet (CAF) for 9 weeks. During the last 4 weeks, obese rats were daily administered with an antibiotic cocktail (ABX), an oral dose of a grape seed proanthocyanidin extract (GSPE), or with their combination. CAF feeding and ABX treatment affected OXLs in a photoperiod dependent-manner. GSPE significantly altered prostaglandin E2 (PGE2) levels, only under L6 and mitigated ABX-mediated effects only under L18. In conclusion, photoperiods affect OXLs levels influenced by gut microbiota. This is the first time that the effects of photoperiod on OXLs metabolites have been demonstrated.

GSPE anti-obesity effects are modulated by the gut microbiota in a photoperiod-dependent manner.

Gut microbiota and biological rhythms are emerging as key factors in the modulation of several physiological and metabolic processes. However, little is known about their interaction and how this may affect host physiology and metabolism. Several studies have shown oscillations of gut microbiota that follows a circadian rhythmicity, but, in contrast, variations due to seasonal rhythms have not been sufficiently investigated yet. Thus, the goal of this study was to investigate the impact of different photoperiods, which mimic seasonal changes, on fecal microbiota composition and how this interaction affects diet-induced obesity development. To this aim, Fisher 344 male rats were housed under three photoperiods (L6, L12 and L18) and fed with standard chow diet or cafeteria diet (CAF) for 9 weeks. The 16S ribosomal sequencing of collected fecal samples was performed. The photoperiod exposure significantly altered the fecal microbiota composition under L18, especially in CAF-fed rats. Moreover, these alterations were associated with changes in body weight gain and different fat parameters. These findings suggest a clear impact of seasonal rhythms on gut microbiota, which ultimately translates into different susceptibilities to diet-induced obesity development. This is the first time to our knowledge that the photoperiod impact on gut microbiota composition has been described in an obesity context although further studies are needed in order to elucidate the mechanisms involved.

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 is 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 are fed either a standard or a cafeteria diet (CAF) for 9 weeks, and an oral dose of GSPE (25 mg kg⁻¹) is daily administered either at 8:00 am (zeitgeber time (ZT)‐0) or at 8:00 pm (ZT‐12) during the last 4 weeks. Plasma phenolic compounds are then quantified by liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC‐ESI‐MS/MS). Phase‐II and gut microbiota‐derived phenolic metabolites are 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 are also observed.Conclusion: These findings demonstrate that ZT, diet, and sex are key factors influencing phenolic compounds bioavailability.