Grape-Seed Procyanidin Extract (GSPE) Seasonal-Dependent Modulation of Glucose and Lipid Metabolism in the Liver of Healthy F344 Rats

Romina M Rodríguez; Marina Colom-Pellicer; Jordi Blanco; Enrique Calvo; Gerard Aragonès; Miquel Mulero

doi:10.3390/biom12060839

Grape-Seed Procyanidin Extract (GSPE) Seasonal-Dependent Modulation of Glucose and Lipid Metabolism in the Liver of Healthy F344 Rats

Biomolecules. 2022 Jun 17;12(6):839. doi: 10.3390/biom12060839.

Authors

Romina M Rodríguez¹, Marina Colom-Pellicer¹, Jordi Blanco², Enrique Calvo¹, Gerard Aragonès¹, Miquel Mulero¹

Affiliations

¹ Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Campus Sescelades, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain.
² Research in Neurobehavior and Health (NEUROLAB), Laboratory of Toxicology and Environmental Health, Physiology Unit, Institute of Health Research Pere Virgili (IISPV), School of Medicine, Universitat Rovira i Virgili (URV), 43202 Tarragona, Spain.

Abstract

Seasonality is gaining attention in the modulation of some physiological and metabolic functions in mammals. Furthermore, the consumption of natural compounds, such as GSPE, is steadily increasing. Consequently, in order to study the interaction of seasonal variations in day length over natural compounds' molecular effects, we carried out an animal study using photo-sensitive rats which were chronically exposed for 9 weeks to three photoperiods (L6, L18, and L12) in order to mimic the day length of different seasons (winter/summer/and autumn-spring). In parallel, animals were also treated either with GSPE 25 (mg/kg) or vehicle (VH) for 4 weeks. Interestingly, a seasonal-dependent GSPE modulation on the hepatic glucose and lipid metabolism was observed. For example, some metabolic genes from the liver (SREBP-1c, Gk, Acacα) changed their expression due to seasonality. Furthermore, the metabolomic results also indicated a seasonal influence on the GSPE effects associated with glucose-6-phosphate, D-glucose, and D-ribose, among others. These differential effects, which were also reflected in some plasmatic parameters (i.e., glucose and triglycerides) and hormones (corticosterone and melatonin), were also associated with significant changes in the expression of several hepatic circadian clock genes (Bmal1, Cry1, and Nr1d1) and ER stress genes (Atf6, Grp78, and Chop). Our results point out the importance of circannual rhythms in regulating metabolic homeostasis and suggest that seasonal variations (long or short photoperiods) affect hepatic metabolism in rats. Furthermore, they suggest that procyanidin consumption could be useful for the modulation of the photoperiod-dependent changes on glucose and lipid metabolism, whose alterations could be related to metabolic diseases (e.g., diabetes, obesity, and cardiovascular disease). Furthermore, even though the GSPE effect is not restricted to a specific photoperiod, our results suggest a more significant effect in the L18 condition.

Keywords: AMPK; GSPE; clock genes; liver; photoperiod; seasonal.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Glucose / metabolism
Grape Seed Extract* / pharmacology
Lipid Metabolism
Liver / metabolism
Mammals / metabolism
Proanthocyanidins* / pharmacology
Rats
Rats, Inbred F344
Seasons
Vitis* / metabolism

Substances

Grape Seed Extract
Proanthocyanidins
Glucose

Grants and funding

This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO), AGL2016-77105-R (CHRONOFOOD project). R.M.R. is recipient of a predoctoral fellowship from Universitat Rovira i Virgili—Martí i Franquès, grant number 2018PMF-PIPF-11. M.C.P. is recipient of a predoctoral fellowship from the Catalan Government, grant number 2021FI_B2 00150. J.B., G.A. and M.M. are Serra-Hunter fellows.