Mixtures of seasonal fruit extracts enriched with (poly)phenols modulate hepatic lipid metabolism in a sex and photoperiod dependent manner in obese rats.

Biological rhythms allow mammals to adapt to environmental light-dark cycles, with photoperiod being a key modulator of metabolism and behavior, influencing body weight, and hepatic lipid metabolism in a sex-dependent manner. In this context, fruit (poly)phenols have been shown to regulate lipid metabolism, improving dyslipidemia in obese rats. Importantly, the metabolic effects of fruits rich in (poly)phenols are strongly influenced by the season of the fruits and the photoperiod. In this study, we evaluated the impact of sex and photoperiod and their interaction on the effects of two mixtures of seasonal fruit extracts enriched with (poly)phenols on hepatic lipid metabolism in obese rats. To this end, a summer mixture (SM; plum and cherry) and a winter mixture (WM; grape and pomegranate) were chronically administered to male and female Fischer 344 rats exposed to short (L6; 6 h light per day) or long (L18; 18 h light per day) photoperiods. Both SM and WM influenced the plasma lipid profile and hepatic expression of genes related to lipogenesis, β-oxidation, and fatty acid transport in a photoperiod- and sex-dependent manner. In male rats, the effects of the SM, characterized by a high content of anthocyanins and hydrolysable tannins, were strongly dependent on the photoperiod. Under L18 conditions, which mimic the fruits' growing season, the SM improved lipid handling and reduced hepatic Ppar-α expression, whereas under L6 conditions, it increased total hepatic cholesterol. Overall, these findings highlight that the bioactivity of dietary (poly)phenols is modulated by temporal and biological factors such as sex and photoperiod, providing new insights into chrononutrition and the development of personalized nutritional strategies to improve metabolic health.