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

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.

Grape-Seed Proanthocyanidins Modulate Adipose Tissue Adaptations to Obesity in a Photoperiod-Dependent Manner in Fischer 344 Rats

“…Moreover, changes in the atmosphere can drive metabolic adaptations in mammals [ 26 ], meaning that seasonal rhythms can impact the effects of (poly)phenol consumption in adipose tissue. However, these effects have not been reported yet, even if evidence exists about the impact of seasonal consumption of (poly)phenols in other metabolic tissues such as the liver or the gut microbiota [ 18 , 19 ]. Our study aimed to elucidate the effects of proanthocyanidin seasonal consumption on the adaptations of the adipose tissue to an obesogenic environment.…”

“…In fact, an influence of photoperiod on the metabolic effects of grape-seed proanthocyanidin extract (GSPE) was recently demonstrated in healthy and obese animals. More specifically, GSPE modulated hepatic glucose and lipid metabolism in a photoperiod-dependent manner [ 18 ]. Moreover, GSPE effects on microbiota were dependent on photoperiod in obese animals [ 19 ].…”

Metabolism disturbance by light/dark cycle switching depends on the rat health status: the role of grape seed flavanols

“…According to this, photoperiod-dependent GSPE effects on CAF-fed rats, more significant under L18 conditions, have been recently reported. 36 Differences in energy intake in CAF-fed rats depending on the photoperiod have also been reported. Specifically, a tendency to increase the energy intake under short compared to long light conditions was observed.…”

“…The F344/IcoCrl rats were seen to be responsive to photoperiods. 31,[35][36][37][38] After two weeks of the acclimatization period, rats were weighted and randomly divided into two groups (n = 24): one group (L12-STD) was fed a STD diet (72% carbohydrates, 8% lipids, and 19% protein; Safe-A04c, Scientific Animal Food and Engineering, Barcelona, Spain), and the other group (L12-CAF) was fed a CAF diet for 6 weeks. After this time, the animals were switched from a L12 to L18 or L6 photoperiod for 1 week.…”

Oligomeric Proanthocyanidins: An Updated Review of Their Natural Sources, Synthesis, and Potentials

“…CVD is a major cause of the increase in the number of deaths, and among the many ways cause this phenomenon includes lipid metabolism and antioxidant levels [92]. GSPE is rich in dimer, trimer, and tetramer OPCs, and the research shows that GSPE can effectively reduce the damage due to free radicals from sodium fluoride in rat kidneys and the lives of healthy F344 rats [93,94]. The GSPE also may correct the imbalance between adipokines and insulin, regulate the physiological function of different adipose tissues, reduce the formation of low-density lipoprotein (LDL), regulate some pathways, and affect the process of cell differentiation to reduce the incidence of obesity, which can increase the morbidity of CVD [95], and the main application areas of oligomeric proanthocyanidins show in Figure 5.…”