Sex- and photoperiod-dependent differences in the bioavailability of (poly)phenols from mixtures of seasonal fruit extracts in obese rats

Obesity and related metabolic disorders are highly prevalent worldwide. (Poly)phenols are bioactive compounds with health-promoting properties, but their activity depends on the processes of absorption, distribution, metabolism, and excretion (ADME), which are modulated by several individual factors, including sex, health status, and photoperiod. Previous studies revealed that photoperiod can influence the bioavailability and bioactivity of (poly)phenol-rich fruits. However, whether these effects extend to mixtures of seasonal fruit extracts remains unknown. This study evaluated how sex and photoperiod affect the bioavailability of (poly)phenols from two multi-ingredient mixtures composed of (poly)phenol-enriched fruit extracts: a winter mixture (WM; grape and pomegranate) and a summer mixture (SM; plum and cherry). Both mixtures were administered to cafeteria diet-induced obese Fischer 344 rats chronically exposed to either a short-day (L6) or a long-day (L18) photoperiod. The two mixtures exhibited markedly different (poly)phenolic profiles, with SM being richer in anthocyanins, hydroxycinnamic acids and total (poly)phenols, and WM containing higher amounts of flavan-3-ols and ellagitannins. The administration of the mixtures to the animals showed that the serum metabolite profiles were dominated by microbiota-derived metabolites. Specific microbial metabolites, unique to each mixture, were detected. Males and females had higher microbial metabolite levels under L6 and L18, respectively, and the administration of WM reduced body weight gain specifically in males under L18. In conclusion, photoperiod and sex jointly influence (poly)phenol bioavailability depending on the mixture of (poly)phenols.