Grape Seed Flavanols Restore Peripheral Clock of White Adipose Tissue in Obese Rats Under Circadian Alterations.

Background: White adipose tissue (WAT) exhibits diurnal oscillations regulated by clock genes, which autonomously control its functionality. These rhythms are modulated by the central clock and external factors, such as light exposure and diet. Flavanols, phenolic compounds known for their beneficial metabolic effects, have been shown to modulate the expression of clock genes. This study explored the impact of flavanols on clock gene expression in WAT explants from lean and obese rats under changes in light/dark cycles. Methods: WAT explants were obtained from 24 Fischer rats fed a standard diet (STD) or cafeteria diet (CAF) for seven weeks. During the final week, rats were changed to short (6 h of light, L6) or long (18 h of light, L18) photoperiods. CAF-fed rats were also administered a grape seed (poly)phenol-rich extract (GSPE) (25 mg/kg) or vehicle (VH). After sacrifice, WAT explants were collected every 6 h starting at 8 a.m. the following day (CT0, CT6, CT12, CT18, and CT24). Results: The results showed that under L18 conditions, STD-fed rats displayed oscillations in Bmal1, Cry1, Per1, and Rev-erbα clock gene expression, whereas many of these rhythms were disrupted under L6 conditions. Moreover, the administration of the CAF diet also resulted in the loss of clock gene circadian oscillations in the WAT explants. GSPE administration restored the oscillation of these clock genes under L18 and L6 conditions. Conclusions: These findings highlight the potential zeitgeber role of flavanols in modulating WAT peripheral clocks and their capacity to improve metabolic and circadian regulation under conditions of diet- and photoperiod-induced disruption.