Exosomes transport trace amounts of (poly)phenols.

(Poly)phenols have varied biological activities that may account for the beneficial effects of fruits and vegetables as part of a healthy diet. Although their cellular absorption and their many mechanisms of action have been partly elucidated, their transport through the systemic circulation, other than their binding to albumin, is poorly described. We aimed at determining whether (poly)phenols can be transported by extracellular vesicles.

Nickel Nanoparticles Induce the Synthesis of a Tumor-Related Polypeptide in Human Epidermal Keratinocytes.

Although nickel allergy and carcinogenicity are well known, their molecular mechanisms are still uncertain, thus demanding studies at the molecular level. The nickel carcinogenicity is known to be dependent on the chemical form of nickel, since only certain nickel compounds can enter the cell. This study investigates, for the first time, the cytotoxicity, cellular uptake, and molecular targets of nickel nanoparticles (NiNPs) in human skin cells in comparison with other chemical forms of nickel.

The Disruption of Liver Metabolic Circadian Rhythms by a Cafeteria Diet Is Sex-Dependent in Fischer 344 Rats.

Circadian rhythms are ~24 h fluctuations of different biological processes that are regulated by the circadian clock system. They exert a major influence on most of the metabolism, such as the hepatic metabolism. This rhythmicity can be disrupted by obesogenic diets, fact that is considered to be a risk factor for the development of metabolic diseases.

5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in , In Vitro and In Vivo Experimental Models.

Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-γ-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism.

The effects of Vitis vinifera L. phenolic compounds on a blood-brain barrier culture model: Expression of leptin receptors and protection against cytokine-induced damage.

Ethnopharmacological Relevance: The medicinal properties of grapes (Vitis vinifera L.) are well known since ancient times. Ethnobotanical grape preparations, like the Ayurvedic Darakchasava are used as cardiotonic and for the treatment of cardiovascular diseases.

Optimization of extraction methods for characterization of phenolic compounds in apricot fruit (Prunus armeniaca).

Fruits are rich in phenolic compounds with health-promoting activities. However, phenolic profiles vary between fruits. Hence, specific extraction methods are required for accurate profiling of the functional compounds.

Intake of an Obesogenic Cafeteria Diet Affects Body Weight, Feeding Behavior, and Glucose and Lipid Metabolism in a Photoperiod-Dependent Manner in F344 Rats.

We previously demonstrated that chronic exposure to different photoperiods induced marked variations in several glucose and lipid metabolism-related parameters in normoweight Fischer 344 (F344) rats. Here, we examined the effects of the combination of an obesogenic cafeteria diet (CAF) and the chronic exposure to three different day lengths (L12, 12 h light/day; L18, 18 h light/day; and L6, 6 h light/day) in this rat strain. Although no changes were observed during the first 4 weeks of adaptation to the different photoperiods in which animals were fed a standard diet, the addition of the CAF for the subsequent 7 weeks triggered profound physiologic and metabolic alterations in a photoperiod-dependent manner.

Potential Involvement of Peripheral Leptin/STAT3 Signaling in the Effects of Resveratrol and Its Metabolites on Reducing Body Fat Accumulation.

Bioactive compounds such as polyphenols have increased in importance in recent years, and among them, resveratrol (3,5,4'-trihydroxy-trans-stilbene) has generated great interest as an anti-obesity agent. Recent investigations have highlighted the importance of leptin signaling in lipid metabolism in peripheral organs. The aims of this study were (1) to investigate whether resveratrol can reduce fat accumulation in peripheral tissues by increasing their leptin sensitivity and (2) to identify which resveratrol-derived circulating metabolites are potentially involved in these metabolic effects.

Cherry consumption out of season alters lipid and glucose homeostasis in normoweight and cafeteria-fed obese Fischer 344 rats.

The xenohormesis theory postulates that animals, through the consumption of chemical cues, mainly polyphenols, synthetized by plants, are able to favorably adapt to changing environmental conditions. We hypothesized that the intake of fruits with a seasonally distinctive phenotype (in terms of bioactive compounds) produced a metabolic response that depends on mammals' circannual rhythms and that fruit intake out of season can lead to a disruption in characteristic seasonal metabolism. Fischer 344 rats were chronically exposed to short (L6, 6 h light/day) and long (L18, 18 h light/day) photoperiods in order to simulate autumn and spring seasons, respectively, and were fed either a standard diet (STD) or an obesogenic cafeteria diet (CAF) and orally treated with either vehicle or 100 mg kg day of lyophilized sweet cherry (Prunus avium L.

Seasonal consumption of polyphenol-rich fruits affects the hypothalamic leptin signaling system in a photoperiod-dependent mode.

Leptin has a central role in the maintenance of energy homeostasis, and its sensitivity is influenced by both the photoperiod and dietary polyphenols. The aim of this study was to investigate the effect of seasonal consumption of polyphenol-rich fruits on the hypothalamic leptin signaling system in non-obese and obese animals placed under different photoperiods. Non-obese and diet-induced obese male Fischer 344 rats were placed under either a short-day (SD) or long-day (LD) photoperiod and were supplemented with either 100 mg/kg of lyophilized red grapes or cherries.

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.

The Exposure to Different Photoperiods Strongly Modulates the Glucose and Lipid Metabolisms of Normoweight Fischer 344 Rats.

Seasonal variations in day length trigger clear changes in the behavior, growth, food intake, and reproductive status of photoperiod-sensitive animals, such as Fischer 344 rats. However, there is little information about the effects of seasonal fluctuations in day length on glucose and lipid metabolisms and their underlying mechanisms in this model. To gain knowledge on these issues, three groups of male Fischer 344 rats were fed with a standard diet and exposed to different photoperiods for 14 weeks: normal photoperiod (L12, 12 h light/day), long photoperiod (L18, 18 h light/day), and short photoperiod (L6, 6 h light/day).

Development and validation of a UHPLC-ESI-MS/MS method for the simultaneous quantification of mammal lysophosphatidylcholines and lysophosphatidylethanolamines in serum.

Recent investigations based on non-targeted metabolomics have proposed lysophospholipids (Lyso-PLs) as biomarkers of different diseases. In particular, lysophosphatidylcholines (Lyso-PCs) and lysophosphatidylethanolamines (Lyso-PEs) have been associated with serious lipid pathologies. Methods to determine the different molecular species in a biological sample and to quantify even less abundant species are required for the evaluation of the Lyso-PL pattern as a novel comprehensive biomarker of dyslipidemia.

Dietary proanthocyanidins boost hepatic NAD(+) metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats.

Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats.

Modulation of leptin resistance by food compounds.

Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity.

Proanthocyanidins in health and disease.

Proanthocyanidins (PAs) are the most abundant flavonoids in the human diet. Several epidemiological studies connect PA consumption and health benefits and the designation of PAs as healthy compounds started at the early stages of the 20th century. The beneficial health properties of PAs are attributed to their conjugated and colonic metabolites.

Dietary proanthocyanidins modulate BMAL1 acetylation, Nampt expression and NAD levels in rat liver.

Metabolism follows circadian rhythms, which are driven by peripheral clocks. Clock genes in the liver are entrained by daytime meals and food components. Proanthocyanidins (PAs), the most abundant flavonoids in the human diet, modulate lipid and glucose metabolism.

Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet-induced obese rats.

Deregulation of miR-33 and miR-122, as major regulators of lipid metabolism in liver, has been related to obesity and metabolic syndrome. Proanthocyanidins repress these microRNAs in healthy animals. Hence, we hypothesized that long-term consumption of dietary proanthocyanidins can normalize the expression of miR-33a and miR-122.

Dietary proanthocyanidins modulate melatonin levels in plasma and the expression pattern of clock genes in the hypothalamus of rats.

Scope: Circadian rhythms allow organisms to anticipate and adapt to environmental changes, and food components can adjust internal rhythms. Proanthocyanidins improve cardiovascular risk factors that exhibit circadian oscillations. Therefore, the aim of the current study was to determine whether proanthocyanidins can modulate body rhythms.

Roles of proanthocyanidin rich extracts in obesity.

Obesity is a multifactorial disorder involving an abnormal or excessive amount of body fat. Obese people have a very high probability of developing metabolic syndrome, a condition in which cholesterol, lipid, and glucose levels rise, causing diabetes and heart disease. From the point of view of energy balance, the main contributors to obesity are excessive energy intake, inadequate energy expenditure and metabolic malfunctions.

Combination of grape seed proanthocyanidin extract and docosahexaenoic acid-rich oil increases the hepatic detoxification by GST mediated GSH conjugation in a lipidic postprandial state.

The ingestion of dietary lipids leads to oxidative stress. This postprandial oxidative stress may potentiate the adverse effects of postprandial hyperlipidaemia. Proanthocyanidins have been shown to alleviate oxidative stress and hypertriglyceridaemia associated with the postprandial state.

microRNAs as new targets of dietary polyphenols.

In the lasts years it has become evident that polyphenols modify cell functionality through epigenetic mechanisms, such as modulating microRNA (miRNA) levels. miRNAs are small non-coding RNAs of about 22 nucleotides in length, that modulate gene expression at the post-transcriptional level. miRNAs are involved in almost all biological processes, affect most metabolic pathways and recent evidence suggests their dysregulation in a number of metabolic disorders and diseases.

Chronic intake of proanthocyanidins and docosahexaenoic acid improves skeletal muscle oxidative capacity in diet-obese rats.

Obesity has become a worldwide epidemic. The cafeteria diet (CD) induces obesity and oxidative-stress-associated insulin resistance. Polyunsaturated fatty acids and polyphenols are dietary compounds that are intensively studied as products that can reduce the health complications related to obesity.

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.