Grape-Seed Proanthocyanidin Extract (GSPE) Modulates Diurnal Rhythms of Hepatic Metabolic Genes and Metabolites, and Reduces Lipid Deposition in Cafeteria-Fed Rats in a Time-of-Day-Dependent Manner

Scope: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health issue with increasing prevalence. Polyphenols, such as grape seed proanthocyanidin extract (GSPE), are bioactive compounds present in plants and represent an interesting therapeutical approach for MASLD. Methods and results: This study questioned whether the timing of GSPE administration impacts liver diurnal metabolism and steatosis in a rat obesity model. Results from hepatic lipid profiling and diurnal metabolic gene expression and metabolomics reveal that rats fed with a cafeteria (CAF) diet show impaired glucose homeostasis and enhanced lipogenesis in the liver, contributing to liver steatosis. Chronic consumption of GSPE in the inactive or active phase is associated with beneficial effects as the restoration of rhythms of transcripts and metabolites is observed. However, only when given in the active phase, GSPE treatment decreases hepatic triglyceride levels. Using an in vitro hepatocyte model, the study identifies that catechin, one of the main phenolic compounds found in the GSPE extract, is a potential mediator in ameliorating the effects of CAF-induced liver steatosis. Conclusion: Taken altogether, the findings show that the beneficial effects of GSPE on MASLD development depend on the treatment time.