Grape Seed Proanthocyanidins Improve White Adipose Tissue Expansion during Diet-Induced Obesity Development in Rats.

The development of metabolic complications associated with obesity has been correlated with a failure of white adipose tissue (WAT) to expand. Our group has previously reported that a 12-week administration of grape seed proanthocyanidin extract (GSPE) together with an obesogenic diet mitigated the development of cardiometabolic complications in rats. Using the same cohort of animals, we aim to elucidate whether the prevention of cardiometabolic complications by proanthocyanidins is produced by a healthier expansion of visceral WAT and/or an induction of the browning of WAT. For this, adipocyte size and number in retroperitoneal WAT (rWAT) were determined by histological analyses, and the gene expression levels of markers of adipogenesis, browning, and WAT functionality were quantified by RT-qPCR. The long-term administration of GSPE together with an obesogenic diet expanded rWAT via an increase in the adipocyte number and a preventive decrease in the adipocyte size in a dose-dependent manner. At the molecular level, GSPE seems to induce WAT adipogenesis through the upregulation of peroxisome proliferator-activated receptor (Pparγ) in a Sirtuin 1 (Sirt1)-dependent manner. In conclusion, the healthier visceral WAT expansion induced by proanthocyanidins supplementation may explain the improvement in the cardiometabolic risks associated with obesogenic diets.

Chronic administration of grape-seed polyphenols attenuates the development of hypertension and improves other cardiometabolic risk factors associated with the metabolic syndrome in cafeteria diet-fed rats.

The effects of grape-seed polyphenols against the development of hypertension and other cardiometabolic conditions associated with the metabolic syndrome (MetS) were studied in rats fed a high-fat, high-carbohydrate diet, known as the cafeteria (CAF) diet. Two groups of Wistar rats were fed standard (STD) or CAF diets for 12 weeks. The CAF diet-fed rats were administered different doses of a low-molecular-weight grape-seed polyphenol extract (LM-GSPE) (25, 100 and 200 mg/kg per d) or vehicle daily, and the STD diet-fed rats were administered LM-GSPE (100 mg/kg per d) or vehicle using ten animals per group. Body weight (BW), waist perimeter (WP) and systolic and diastolic blood pressures (BP) by the tail-cuff method were recorded weekly. The animals were housed in metabolic chambers every 2 weeks to estimate daily food and liquid intakes and to collect faeces and urine samples. The plasma lipid profile was analysed at time 0 and on the 4th, 7th, 10th and 12th weeks of the experiment. Moreover, plasma leptin was measured at the end of the experiment. Results demonstrated that LM-GSPE, when administered with the CAF diet, attenuated the increase in BP, BW, WP and improved lipid metabolism in these animals. However, although the 25- and 100-mg/kg per d doses were sufficient to produce beneficial effects on BP and lipid metabolism, a 200-mg/kg per d dose was necessary to have an effect on BW and WP. The present findings suggest that LM-GSPE is a good candidate for a BP-lowering agent that can also ameliorate other conditions associated with the MetS.

Acute administration of single oral dose of grape seed polyphenols restores blood pressure in a rat model of metabolic syndrome: role of nitric oxide and prostacyclin.

PURPOSE: The aims of this study were to evaluate the antihypertensive effectiveness of different doses of grape seed polyphenols in cafeteria diet-fed hypertensive rats (CHRs) and to establish the mechanism involved in the blood pressure (BP) lowering effect of these compounds in this experimental model of metabolic syndrome (MS). METHODS: Male 8-week-old Wistar rats were fed cafeteria or standard (ST) diet for 10 weeks. After this, the antihypertensive effect of a single oral administration of a polyphenol grape seed extract (GSPE) was tested at different doses (250, 375 and 500 mg/kg) in CHRs. BP was recorded before and 2, 4, 6, 8, 24 and 48 h post-administration. The hypotensive effect of GSPE was also proved in ST diet-fed rats. Additionally, in other experiment, CHRs were orally administered 375 mg/kg GSPE. Four hours post-administration, the rats were intraperitoneally administrated 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) or 5 mg/kg indomethacin [inhibitors of nitric oxide (NO) and prostacyclin synthesis, respectively]. BP was recorded initially and 6 h post-administration. RESULTS: GSPE produced a decrease in SBP and DBP, the most effective dose (375 mg/kg) showing an antihypertensive effect in CHRs similar to the drug captopril, and did not affect BP of ST diet-fed rats. The antihypertensive effect was completely abolished by L-NAME and partially inhibited by indomethacin. CONCLUSIONS: GSPE acts as an antihypertensive agent in a rat model of hypertension associated with MS. The change in endothelium-derived NO availability is one of the mechanisms involved in the antihypertensive effect of GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of GSPE on arterial BP.

Resveratrol and EGCG bind directly and distinctively to miR-33a and miR-122 and modulate divergently their levels in hepatic cells.

Modulation of miR-33 and miR-122 has been proposed to be a promising strategy to treat dyslipidemia and insulin resistance associated with obesity and metabolic syndrome. Interestingly, specific polyphenols reduce the levels of these mi(cro)RNAs. The aim of this study was to elucidate the effect of polyphenols of different chemical structure on miR-33a and miR-122 expression and to determine whether direct binding of the polyphenol to the mature microRNAs (miRNAs) is a plausible mechanism of modulation. The effect of two grape proanthocyanidin extracts, their fractions and pure polyphenol compounds on miRNA expression was evaluated using hepatic cell lines. Results demonstrated that the effect on miRNA expression depended on the polyphenol chemical structure. Moreover, miR-33a was repressed independently of its host-gene SREBP2. Therefore, the ability of resveratrol and epigallocatechin gallate to bind miR-33a and miR-122 was measured using (1)H NMR spectroscopy. Both compounds bound miR-33a and miR-122 and differently. Interestingly, the nature of the binding of these compounds to the miRNAs was consistent with their effects on cell miRNA levels. Therefore, the specific and direct binding of polyphenols to miRNAs emerges as a new posttranscriptional mechanism by which polyphenols could modulate metabolism.

Epigallocatechin gallate counteracts oxidative stress in docosahexaenoxic acid-treated myocytes.

Skeletal muscle is a key organ of mammalian energy metabolism, and its mitochondria are multifunction organelles that are targets of dietary bioactive compounds. The goal of this work was to examine the regulation of mitochondrial dynamics, functionality and cell energy parameters using docosahexaenoic acid (DHA), epigallocatechin gallate (EGCG) and a combination of both in L6 myocytes. Compounds (at 25µM) were incubated for 4h. Cells cultured with DHA displayed less oxygen consumption with higher ADP/ATP ratio levels concomitant with downregulation of Cox and Ant1 gene expression. The disruption of energetic homeostasis by DHA, increases intracellular reactive oxygen species (ROS) levels and decreases mitochondrial membrane potential. The defence mechanism to counteract the excess of ROS production was by the upregulation of Ucp2, Ucp3 and MnSod gene expression. Moreover myocytes cultured with DHA had a higher mitochondrial mass with a higher proportion of large and elongated mitochondria, whereas the fission genes Drp1 and Fiss1 and the fusion gene Mfn2 were downregulated. In myocytes co-incubated with DHA and EGCG, ROS levels and the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio were similar to untreated myocytes and the decrease of oxygen consumption, higher mitochondrial mass and the overexpression of Ucp2 and Ucp3 genes were similar to the DHA-treated cells with also a higher amount of mitochondrial deoxyribonucleic acid (DNA), and reduced Drp1 and Fiss1 gene expression levels. In conclusion the addition of EGCG to DHA returned the cells to the control conditions in terms of mitochondrial morphology, energy and redox status, which were unbalanced in the DHA-treated myocytes.

Differential effects of habitual chow-based and semi-purified diets on lipid metabolism in lactating rats and their offspring.

Diet during pregnancy and lactation is a critical factor in relation to the health of dams and their offspring. Currently, control diets used in metabolic imprinting studies differ in composition and type, i.e. semi-purified diets (SD) or chow-based diets (ND). The aim of the present study was to determine whether two widely used control diets, a SD and a ND, that mainly differ in fat content (5·08 and 3·26 %, respectively) and its sources (soyabean oil for the SD and cereals and fish for the ND), fibre (6 and 15 %, respectively), and cholesterol (26 and 69 mg/kg diet, respectively) can influence the lipid metabolism of dams and their offspring. Wistar rats were fed either the SD or the ND during pregnancy and lactation. At weaning, SD-fed dams presented severe hepatic steatosis and increased levels of circulating TAG, NEFA and insulin. Importantly, the offspring presented an altered plasma lipid profile. In contrast, the ND allowed for a normal gestation and lactation process, and did not affect the metabolism of offspring. In parallel, virgin rats fed the SD showed no metabolic alterations. A higher intake of SFA and MUFA and a lower consumption of PUFA observed in SD-fed dams during the lactation period could contribute to explaining the observed effects. In conclusion, two different control diets produced very different outcomes in the lipid metabolism of lactating rats and their offspring. The present results highlight the importance of the assessment of the metabolic state of dams when interpreting the results of metabolic programming studies.

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

Seasonal rhythms drive metabolic adaptations that influence body weight and adiposity. Adipose tissue is a key regulator of energy homeostasis in the organism, and its healthiness is needed to prevent the major consequences of overweight and obesity. In this context, supplementation with proanthocyanidins has been postulated as a potential strategy to prevent the alterations caused by obesity. Moreover, the effects of these (poly)phenols on metabolism are photoperiod dependent. In order to describe the impact of grape-seed proanthocyanidins extract (GSPE) on important markers of adipose tissue functionality under an obesogenic environment, we exposed Fischer 344 rats to three different photoperiods and fed them a cafeteria diet for five weeks. Afterwards, we supplemented them with 25 mg GSPE/kg/day for four weeks. Our results revealed that GSPE supplementation prevented excessive body weight gain under a long photoperiod, which could be explained by increased lipolysis in the adipose tissue. Moreover, cholesterol and non-esterified fatty acids (NEFAs) serum concentrations were restored by GSPE under standard photoperiod. GSPE consumption slightly helped combat the obesity-induced hypertrophy in adipocytes, and adiponectin mRNA levels were upregulated under all photoperiods. Overall, the administration of GSPE helped reduce the impact of obesity in the adipose tissue, depending on the photoperiod at which GSPE was consumed and on the type of adipose depots.

Photoperiod Conditions Modulate Serum Oxylipins Levels in Healthy and Obese Rats: Impact of Proanthocyanidins and Gut Microbiota.

Seasonal rhythms are emerging as a key factor influencing gut microbiota and bioactive compounds functionality as well as several physiological processes such as inflammation. In this regard, their impact on the modulation of oxylipins (OXLs), which are important lipid mediators of inflammatory processes, has not been investigated yet. Hence, we aimed to investigate the effects of photoperiods on OXLs metabolites in healthy and obesogenic conditions. Moreover, we evaluated if the impact of proanthocyanidins and gut microbiota on OXLs metabolism is influenced by photoperiod in obesity. To this purpose, Fischer 344 rats were housed under different photoperiod conditions (L6: 6 h light, L12: 12 h light or L18:18 h light) and fed either a standard chow diet (STD) or a cafeteria diet (CAF) for 9 weeks. During the last 4 weeks, obese rats were daily administered with an antibiotic cocktail (ABX), an oral dose of a grape seed proanthocyanidin extract (GSPE), or with their combination. CAF feeding and ABX treatment affected OXLs in a photoperiod dependent-manner. GSPE significantly altered prostaglandin E2 (PGE2) levels, only under L6 and mitigated ABX-mediated effects only under L18. In conclusion, photoperiods affect OXLs levels influenced by gut microbiota. This is the first time that the effects of photoperiod on OXLs metabolites have been demonstrated.

Gut Microbiota Influences the Photoperiod Effects on Proanthocyanidins Bioavailability in Diet-Induced Obese Rats.

SCOPE: Polyphenols health effects on obesity are mainly attributed to their metabolites generated after their gastrointestinal digestion, in which gut microbiota plays an important role. Moreover, gut microbiota composition and polyphenols bioavailability are influenced by differences in day light length (photoperiod). Thus, this study evaluates if a grape seed proanthocyanidins (GSPEs) extract bioavailability is influenced by different photoperiod exposure via gut microbiota modulation in an obesogenic context. METHODS AND RESULTS: Cafeteria diet-induced obese Fischer 344 rats are housed under different photoperiod conditions (6, 12, or 18 h of light per day) during 9 weeks and administered with GSPE (25 mg kg-1 ) or GSPE and an antibiotic cocktail (ABX) for the last 4 weeks. Serum GSPE-derived metabolites are quantified by HPLC-MS/MS. CONCLUSION: A higher bioavailability is observed under 6 h light/18 h darkness (L6) compared to 18 h light/6 h darkness (L18). Individual metabolites, especially those from the gut microbiota, are affected by photoperiods. ABX treatment alters these photoperiod-mediated changes. Therefore, these results suggest that gut microbiota plays a key role in the photoperiod effects on GSPE bioavailability in obese rats.

Organic vs. Non-Organic Plant-Based Foods-A Comparative Study on Phenolic Content and Antioxidant Capacity.

A plant's stress response involves the production of phytochemicals, including phenolic compounds. Their synthesis can be modulated by organic (ORG) or non-organic (NORG) farming systems in which they are grown. To examine this issue, thirteen plant-based foods cultivated in ORG and NORG systems were compared in terms of antioxidant capacity, total content of phenolics, anthocyanins, flavan-3-ols and flavonols. The results showed that NORG fruits tended to have higher phenolic compounds content, whereas ORG fruits had more antioxidant capacity. NORG legume stood out for having higher values from all the parameters analyzed in comparison to its ORG equivalent. ORG nuts showed more flavan-3-ols and flavonols than their NORG counterparts, nonetheless, tended to be less antioxidant. ORG vegetables displayed higher phenolics and anthocyanins, which reflected in higher antioxidant capacity than NORG ones. These findings suggest that farming systems differentially modulate phenolic compound composition and antioxidant capacity based on the plant species studied.

Fatty acid metabolism in liver and muscle is strongly modulated by photoperiod in Fischer 344 rats.

Circadian and seasonal variations produce variations in physiological processes throughout the day and the year, respectively. In this sense, both the light and the moment of feeding are strong modulators of the central and peripheral clocks. However, little is known about its influence on certain metabolic parameters and on the composition of liver and muscle fatty acids (FA). In the present study, 24 Fischer 344 rats were exposed for 11 weeks to different photoperiods, L6, L12 and L18, with 6, 12 and 18 h of light/day, respectively. They were fed a standard diet. Serum metabolic parameters, gene expression of liver enzymes and gastrocnemius muscle involved in the synthesis, elongation, desaturation and ß-oxidation of FA were analyzed. We have found that exposure to different hours of light has a clear effect on FA composition and gene expression in the liver. Mainly, the biosynthesis of unsaturated FA was altered in the L18 animals with respect to those exposed to L12, while the L6 did not show significant changes. At the muscle level, differences were observed in the concentration of mono and polyunsaturated FA. A multivariate analysis confirmed the differences between L12 and L18 in a significant way. We conclude that exposure to long days produces changes in the composition of liver and muscle FA, as well as changes in the gene expression of oxidative enzymes compared to exposure to L12, which could be a consequence of different seasonal eating patterns.

Administration time effect of dietary proanthocyanidins on the metabolome of Fischer 344 rats is sex- and diet-dependent.

Proanthocyanidins (PAs) are one of the most commonly ingested polyphenols in the human diet, with a wide range of beneficial health effects. Remarkably, PAs have been reported to influence core and peripheral clock genes expression, and their effects may change in a time-of-day dependent manner. Therefore, the aim of this study was to investigate whether the capacity of PAs to modulate the metabolome is conditioned by the time-of-day in which these compounds are consumed in a diet- and sex-dependent manner. To do this, a grape seed proanthocyanidin extract (GSPE) was administered to female and male Fischer 344 rats at ZT0 (in the morning) and ZT12 (at night) and the GSPE administration time effect was evaluated on clock genes expression, melatonin hormone and serum metabolite levels in a healthy and obesogenic context. The results showed an administration time effect of GSPE on the metabolome in a sex and diet-dependent manner. Specifically, there was an effect on amino acid, lipid and cholate metabolite levels that correlated with the central clock genes expression. Therefore, this study shows a strong influence of sex and diet on the PAs effects on the metabolome, modulated in turn by the time-of-day.

Chronic dietary supplementation of proanthocyanidins corrects the mitochondrial dysfunction of brown adipose tissue caused by diet-induced obesity in Wistar rats.

The present study aims to determine the effects of grape seed proanthocyanidin extract (GSPE) on brown adipose tissue (BAT) mitochondrial function in a state of obesity induced by diet. Wistar male rats were fed with a cafeteria diet (Cd) for 4 months; during the last 21 d, two groups were treated with doses of 25 and 50 mg GSPE/kg body weight. In the BAT, enzymatic activities of citrate synthase, cytochrome c oxidase (COX) and ATPase were determined and gene expression was analysed by real-time PCR. The mitochondrial function of BAT was determined in fresh mitochondria by high-resolution respirometry using both pyruvate and carnitine-palmitoyl-CoA as substrates. The results show that the Cd causes an important decrease in the gene expression of sirtuin 1, nuclear respiratory factor 1, isocitrate dehydrogenase 3γ and COX5α and, what is more telling, decreases the levels of mitochondrial respiration both with pyruvate and canitine-palmitoyl-CoA. Most of these parameters, which are indicative of mitochondrial dysfunction due to diet-induced obesity, are improved by chronic supplementation of GSPE. The beneficial effects caused by the administration of GSPE are exhibited as a protection against weight gain, in spite of the Cd the rats were fed. These data indicate that chronic consumption of a moderate dose of GSPE can correct an energy imbalance in a situation of diet-induced obesity, thereby improving the mitochondrial function and thermogenic capacity of the BAT.

Do You Have Problems When Reproducing Bioactivities of Food or Food Components? The Importance of Biological Rhythms.

With the onset of omics sciences, in the 20th century, nutritional studies evolved to investigate the effects of diet at a molecular level, giving rise to nutritional genomics, which includes both nutrigenomics and nutrigenetics [...].

Impact of Seasonal Consumption of Local Tomatoes on the Metabolism and Absorption of (Poly)Phenols in Fischer Rats.

Consuming (poly)phenol-rich fruits and vegetables, including tomato, is associated with health benefits. The health effects of tomato (poly)phenolic compounds have been attributed to their metabolites rather than parent compounds and their bioavailability can be modulated by several factors. This study aimed to evaluate the effect of seasonal consumption of local tomatoes on their (poly)phenol bioavailability. For this, (poly)phenol absorption and metabolism were evaluated by ultra-high-performance liquid chromatography coupled with mass spectrometry and linear ion trap mass spectrometric (uHPLC-MSn) after chronic tomato consumption in Fischer rats exposed to three photoperiods mimicking the seasonal daylight schedule. Tomatoes from two locations in Spain (LT, local tomatoes and NLT, non-local tomatoes) were used in this in vivo feeding study. The bioavailability of tomato (poly)phenols depended on the photoperiod to which the rats were exposed, the metabolite concentrations significantly varying between seasons. In-season tomato consumption allowed obtaining the highest concentration of total circulating metabolites. In addition, the origin of the tomato administered generated marked differences in the metabolic profiles, with higher serum concentrations reached upon NLT ingestion. We concluded that in-season tomato consumption led to an increase in (poly)phenol circulation, whereas LT consumption showed lower circulating metabolites than NLT ones. Thus, the origin of the tomato and the seasonal daylight schedule affect the bioavailability of tomato (poly)phenols, which could also affect their bioactivity.

Gut Seasons: Photoperiod Effects on Fecal Microbiota in Healthy and Cafeteria-Induced Obese Fisher 344 Rats.

Gut microbiota and biological rhythms are emerging as key factors in the modulation of several physiological and metabolic processes. However, little is known about their interaction and how this may affect host physiology and metabolism. Several studies have shown oscillations of gut microbiota that follows a circadian rhythmicity, but, in contrast, variations due to seasonal rhythms have not been sufficiently investigated yet. Thus, the goal of this study was to investigate the impact of different photoperiods, which mimic seasonal changes, on fecal microbiota composition and how this interaction affects diet-induced obesity development. To this aim, Fisher 344 male rats were housed under three photoperiods (L6, L12 and L18) and fed with standard chow diet or cafeteria diet (CAF) for 9 weeks. The 16S ribosomal sequencing of collected fecal samples was performed. The photoperiod exposure significantly altered the fecal microbiota composition under L18, especially in CAF-fed rats. Moreover, these alterations were associated with changes in body weight gain and different fat parameters. These findings suggest a clear impact of seasonal rhythms on gut microbiota, which ultimately translates into different susceptibilities to diet-induced obesity development. This is the first time to our knowledge that the photoperiod impact on gut microbiota composition has been described in an obesity context although further studies are needed in order to elucidate the mechanisms involved.

(Poly)phenolic composition of tomatoes from different growing locations and their absorption in rats: A comparative study.

The aim of this work was to address whether the growing location of tomato could generate a different (poly)phenol profile able to affect both in vivo absorption and (poly)phenol metabolite pattern upon tomato consumption. uHPLC-MSn analyses allowed to obtain a detailed (poly)phenol profile of tomatoes from two locations in Spain, quantifying 57 (poly)phenolic compounds. However, local and non-local tomatoes showed a different concentration of their native (poly)phenols, which could be attributed to diverse cultivation origin. Rat serum was analysed after an acute tomato feeding. Seven phenolic metabolites were quantified through uHPLC-MSn. Pharmacokinetic parameters were further evaluated, revealing different serum concentrations of (poly)phenolic metabolites between tomatoes. The maximum peak serum concentrations, reached mainly after 2 h after ingestion, led to suppose that serum metabolites were mostly derived from absorption in the upper gastrointestinal tract. The growing location of tomatoes affected both the content of native (poly)phenols and their in vivo absorption.

Administration Time Significantly Affects Plasma Bioavailability of Grape Seed Proanthocyanidins Extract in Healthy and Obese Fischer 344 Rats.

SCOPE: Phenolic compounds are bioactive molecules that are associated with several health benefits. Metabolization and absorption are the main determinants of their bioavailability and bioactivity. Thus, the study of the factors that modulate these processes, such as sex or diet is essential. Recently, it has been shown that biological rhythms may also play a key role. Hence, the aim of this study is to evaluate if the bioavailability of a grape proanthocyanidin extract (GSPE) is affected by the administration time in an animal model of metabolic syndrome (MetS). METHODS AND RESULTS: Female and male Fischer 344 rats are fed either a standard or a cafeteria diet (CAF) for 9 weeks, and an oral dose of GSPE (25 mg kg-1 ) is daily administered either at 8:00 am (zeitgeber time (ZT)-0) or at 8:00 pm (ZT-12) during the last 4 weeks. Plasma phenolic compounds are then quantified by liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Phase-II and gut microbiota-derived phenolic metabolites are affected by ZT in all conditions or only in obese rats, respectively. CAF feeding affected the bioavailability of phenolic acids and free flavan-3-ols. Differences due to sex are also observed. CONCLUSION: These findings demonstrate that ZT, diet, and sex are key factors influencing phenolic compounds bioavailability.

The effects of grape seed proanthocyanidins in cafeteria diet-induced obese Fischer 344 rats are influenced by faecal microbiota in a photoperiod dependent manner.

Polyphenols are of high interest due to their beneficial health effects, including anti-obesity properties. The gut microbiota may play an important role in polyphenol-mediated effects as these bacteria are significantly involved in the metabolism of polyphenols. Moreover, seasonal rhythms have been demonstrated to influence both the gut microbiota composition and polyphenol bioavailability. Thus, the goal of this study was to evaluate the impact of photoperiods and microbiota on polyphenol functionality in an obesogenic context. Towards this aim, cafeteria diet-fed Fischer 344 rats were housed under three different photoperiod conditions (L6: 6 h of light, L12: 12 h of light and L18: 18 h of light) for 9 weeks. During the last 4 weeks of the experiment, rats were daily administered with an oral dose of a grape seed proanthocyanidin extract (GSPE) (25 mg per kg body weight). Additionally, rats treated with GSPE and an antibiotic cocktail (ABX) in their drinking water were included for a better understanding of the gut microbiota role in GSPE functionality. Vehicle and non-ABX treated rats were included as controls. GSPE decreased body weight gain and fat depots only under L18 conditions. Interestingly, the gut microbiota composition was strongly altered in this photoperiod. GSPE + ABX-treated rats gained significantly less body weight compared to the rats of the rest of the treatments under L18 conditions. These results suggest that GSPE functionality is modulated by the gut microbiota in a photoperiod dependent manner. These novel findings corroborate seasonal rhythms as key factors that must be taken into account when investigating the effects of polyphenols in the treatment or prevention of chronic diseases.

In-Season Consumption of Locally Produced Tomatoes Decreases Cardiovascular Risk Indices.

Tomatoes are widely consumed worldwide at any time of the year. However, depending on the variety, they have a characteristic season. We evaluated the consequences metabolic of consumption of Ekstasis tomatoes from different geographical origin and in different seasons in Fischer 344 rats. The hepatic gene expression of key enzymes in lipid metabolism was also evaluated. Animals were classified in three photoperiods (L6, L12, and L18) and in three treatments (vehicle: VH; local tomato: LT; and non-local tomato: nLT). We measured serum metabolic parameters and the gene expression of liver enzymes related to lipid metabolism (Acc1, Cpt1a, Had, Fas1, Srebp-1c, Fatp5, Cd36). LT consumption in season decreased cardiovascular risk 1 and coefficient atherogenic by 1.81 (p = 0.031) and in L6 decreased TAG and glucose (p = 0.046; p = 0.024). The L18-LT animals had decreased total cholesterol (p = 0.029) and gene expression of Srebp1-c (p = 0.022) but increased expression of Acc1 (p = 0.032). The treatments significantly affected the expression of Acc1 and Fas1 in the liver and the levels of serum TAG and glucose. A significant effect of photoperiod on serum concentration of glucose, insulin, HOMA index, and on the hepatic expression of Srep1-c, Fas1, and Acc1 was observed.