Ingestion of Bean Leaves Reduces Metabolic Complications and Restores Intestinal Integrity in C57BL/6 Mice with Obesity Induced by a High-Fat and High-Fructose Diet.

Consumption of foods with fiber and compounds can promote gastrointestinal health and reduce obesity complications. Therefore, treatment with common bean leaves (BL) against obesity was evaluated in mice with a high-fat and high-fructose diet (HFFD) for 14 weeks. The bromatological and phytochemical characterization of BL were determined. Afterwards, the animals were supplemented with BL (10%) or a standard diet (SD) as a strategy to encourage a healthy diet for 12 additional weeks. Changes in body composition, lipid profile, and intestinal integrity were analyzed. The characterization of BL stood out for its content of 27.2% dietary fiber, total phenolics (475.04 mg/100 g), and saponins (2.2 mg/100 g). The visceral adipose tissue (VAT) decreased in the BL group by 52% compared to the HFFD group. Additionally, triglyceride levels were 23% lower in the BL consumption group compared to the HFFD group. The improvement in lipid profile was attributed to the 1.77-fold higher fecal lipid excretion in the BL consumption group compared to the HFFD group and the inhibition of pancreatic lipase by 29%. Furthermore, BL supplementation reduced the serum levels of IL-6 (4.4-fold) and FITC-dextran by 50% compared with those in the HFFD group. Metabolic endotoxemia was inhibited after BL supplementation (-33%) compared to the HFFD group. BL consumption as a treatment in obese mice reduces adipose tissue accumulation and improves the lipid profile. Furthermore, we report for the first time that BL consumption improves intestinal integrity.

Impact of temperature and humidity conditions as abiotic stressors on the phytochemical fingerprint of oat (Avena sativa L.) sprouts.

This study aimed to evaluate the effect of temperature (20, 25, and 30 °C) and relative humidity (RH, 50, 55, and 60 %) as abiotic stressors during oat (Avena sativa L.) germination using a 2-level factorial design with central point. UPLC-QToF-MSE identified eighty polyphenols, nine avenanthramides, twelve lignans, and five phytosterols Notably, 100 % germination was achieved at 25 °C/60 % RH from day 3, yielding the longest radicle size. The highest content of most phenolic acids, avenanthramides, and lignans occurred at 30 °C/65 % RH, where 100 % germination was attained by day 5, but with a shorter radicle size. The best flavonoid and phytosterol profle was obtained at 20 °C/55 % RH, achieving only a 67 % germination rate. Therefore, while these conditions enhance the bioactive compound profile, the associate decrease in germination metrics suggests potential distress effects. Consideration of both photochemical outcomes and germination yield is crucial for comprehensive assessments in future applications.

A New Approach Using BMI and FMI as Predictors of Cardio-Vascular Risk Factors among Mexican Young Adults.

The study aimed to identify accurate cut-off points for waist circumference (WC), body fat percentage (BF%), body mass index (BMI), fat mass index (FMI), and fat-free mass index (FFMI), and to determine their effective accuracy to predict cardiovascular risk factors (CVRFs) among Mexican young adults. A cross-sectional study was conducted among 1730 Mexican young adults. Adiposity measures and CVRFs were assessed under fasting conditions. The optimal cut-off points were assessed using the receiver operating characteristic curve (ROC). Age-adjusted odds ratios (OR) were used to assess the associations between anthropometric measurements and CVRFs. The cut-off values found, in females and males, respectively, for high WC (≥72.3 and ≥84.9), high BF% (≥30 and ≥22.6), high BMI (≥23.7 and ≥24.4), high FMI (≥7.1 and ≥5.5), and low FFMI (≤16 and ≤18.9) differ from those set by current guidelines. High BMI in women, and high FMI in men, assessed by the 50th percentile, had the best discriminatory power in detecting CVRFs, especially high triglycerides (OR: 3.07, CI: 2.21-4.27 and OR: 3.05, CI: 2.28-4.08, respectively). Therefore, these results suggest that BMI and FMI measures should be used to improve the screening of CVRFs in Mexican young adults.

Phytochemical Profile and Composition of Chickpea (Cicer arietinum L.): Varietal Differences and Effect of Germination under Elicited Conditions.

Germination is a simple process that improves the nutritional and medicinal values of seeds such as chickpeas. However, the detailed analysis of the phytochemical profile after chemical elicitation during chickpea germination is indispensable when making inferences about its biological properties. Therefore, an evaluation was made of the effect of the chemical inducers salicylic acid (SA, 1 and 2 mM), chitosan (CH, 3.3 and 7 µM), and hydrogen peroxide (H2O2, 20 and 30 mM) during germination at 25 °C with 70% RH for 4 days on the content of antinutritional and bioactive compounds, including phenolics, sterols, and saponins, in three Mexican chickpea varieties (Blanoro, Patron, and San Antonio) using UPLC-ELSD-ESI-QqQ-MS/MS, UPLC-DAD-ESI-QqQ-MS/MS, and HPLC-DAD-sQ-MS. The highest increase in phenolics and saponins was found in the Blanoro sprouts induced with SA 2 mM, whereas the highest phytosterol content was detected in San Antonio sprouts induced with CH 7 µM. In addition, significant increases in mono-, di-, and oligosaccharides and decreases in antinutritional contents were achieved after germination with most of the elicitation conditions. More importantly, we identified new compounds in chickpea sprouts, such as the lignans matairesinol and secoisolariciresinol, the phenolic compounds epicatechin gallate and methyl gallate, some phytosterols, and the saponin phaseoside 1, which further increased after chemical elicitation.

Macrophage Activity under Hyperglycemia: A Study of the Effect of Resveratrol and 3H-1,2-Dithiole-3-thione on Potential Polarization.

Currently, research is focused on bioactive compounds with the potential to promote macrophage polarization with the aim of reducing the development of inflammatory-related diseases. However, the effect of bioactive compounds under oxidative-stress-induced hyperglycemia on macrophage polarization has been scarcely investigated. RAW 264.7 macrophages were incubated under standard (SG) or high glucose (HG) conditions and stimulated with lipopolysaccharide (LPS) (10, 60 and 100 ng/mL) to monitor macrophage polarization after resveratrol (RSV) or 3H-1,2-dithiole-3-thione (D3T) supplementation (2.5, 5, 10 and 20 µM). Under SG and HG conditions without LPS stimulation, RSV significantly decreased macrophage viability at the highest concentration (20 µM), whereas D3T had no or low effect. LPS stimulation at 60 and 100 ng/mL, under SG and HG conditions, increased significantly macrophage viability. Both RSV and D3T significantly decreased NO production in LPS-stimulated macrophages under HG condition, whereas only D3T increased GSH levels at 100 ng/mL and normalized MDA values at 60 ng/mL of LPS under HG condition. Under 60 ng/mL LPS stimulation and HG, mRNA IL-1 and IL-6 were higher. Interestingly, RSV decreased pro-inflammatory interleukins; meanwhile, D3T increased Arg1 and IL-10 relative expression. Overall, our results indicate that hyperglycemia plays a fundamental role in the modulation of macrophage-induced inflammation in response to bioactive compounds.

Bean Leaves Ameliorate Lipotoxicity in Fatty Liver Disease.

Bioactive compounds in plant-based food have protective effects against metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Bean leaves are widely cultivated in the world and are a source of dietary fiber and polyphenols. High fat/high fructose diet animal models promote deleterious effects in adipose and non-adipose tissues (lipotoxicity), leading to obesity and its comorbidities. Short-term supplementation of bean leaves exhibited anti-diabetic, anti-hyperlipidemic, and anti-obesity effects in high-fat/high-fructose diet animal models. This study aimed to evaluate the effect of bean leaves supplementation in the prevention of lipotoxicity in NAFLD and contribute to elucidating the possible mechanism involved for a longer period of time. During thirteen weeks, male Wistar rats (n = 9/group) were fed with: (1) S: Rodent Laboratory Chow 5001® (RLC); (2) SBL: 90% RLC+ 10% dry bean leaves; (3) H: high-fat/high-fructose diet; (4) HBL: H+ 10% of dry bean leaves. Overall, a HBL diet enhanced impaired glucose tolerance and ameliorated obesity, risk factors in NAFLD development. Additionally, bean leaves exerted antioxidant (↑serum GSH) and anti-inflammatory (↓mRNA TNFα in the liver) effects, prevented hepatic fat accumulation by enhanced ↑mRNA PPARα (ß oxidation), and enhanced lipid peroxidation (↓liver MDA). These findings suggest that bean leaves ameliorated hepatic lipotoxicity derived from the consumption of a deleterious diet.

Beverage Consumption Patterns and Nutrient Intake Are Associated with Cardiovascular Risk Factors among Urban Mexican Young Adults.

Regular consumption of sugar-sweetened beverages has been related to metabolic diseases. Our objective was to identify beverage consumption patterns, nutrient intake, and their possible association with the prevalence of cardiovascular risk factors among Mexican young adults. A cross-sectional survey was conducted. Beverage consumption patterns were obtained by principal components analysis. Logistic regression models were applied to assess the association between the beverage patterns and cardiovascular risk factors. Four beverage patterns were identified. Higher consumption of alcoholic beverages was associated with lower odds for high body fat percent (OR: 0.371; 95% CI: 0.173-0.798), high blood pressure (OR: 0.318; 95% CI: 0.116-0.871), and high glucose (OR: 0.232; 95% CI: 0.061-0.875). Higher consumption of yogurt was associated with lower odds for high glucose (OR: 0.110; 95% CI: 0.22-0.559). In contrast, highest consumption of juice had greater odds for high triglycerides (OR: 1.084; 95% CI: 1.011-4.656). Higher consumption of milk was associated with greater odds for high glucose (OR: 5.304; 95% CI: 1.292-21.773). Beverage consumption habits in Mexican young adults are associated with increased risk factors for cardiovascular disease. Therefore, intervening during young adulthood should be considered in order to improve current health and prevent cardiovascular mortality in later decades.

Bioactive Compounds and Adipocyte Browning Phenomenon.

Overweight and obesity have become worldwide health issues in most countries. Current strategies aimed to prevent or reduce overweight and obesity have mainly focused on the genes and molecular mechanisms that give the functional characteristics to different types of adipose tissue. The Browning phenomenon in adipocytes consists of phenotypic and metabolic changes within white adipose tissue (WAT) activated by thermogenic mechanisms similar to that occurring in brown adipose tissue (BAT); this phenomenon has assumed great relevance due to its therapeutic potential against overweight and obesity. In addition, the study of inflammation in the development of overweight and obesity has also been included as a relevant factor, such as the pro-inflammatory mechanisms promoted by M1-type macrophages in adipose tissue. Studies carried out in this area are mainly performed by using the 3T3-L1 pre-adipocyte cell line, testing different bioactive compound sources such as plants and foods; nevertheless, it is necessary to standardize protocols used in vitro as well to properly scale them to animal models and clinical tests in order to have a better understanding of the mechanisms involved in overweight and obesity.

Consumption of cricket (Acheta domesticus) flour decreases insulin resistance and fat accumulation in rats fed with high-fat and -fructose diet.

The consumption of cricket (Acheta domesticus, AD) has recently increased due to its high nutritional and bioactive compound contents. However, limited studies have explored the beneficial effects of AD consumption. Therefore, we aimed to evaluate the protective effect of a diet supplemented with AD flour on obesity control and its complications in an in vivo model. The chemical profiling of the AD showed an important protein content, chitin, and polyunsaturated fatty acids contents. For the in vivo study, a high-fructose and saturated fat diet (HFFD) was supplemented with AD (4% and 8%). The 8% AD supplementation reduced body weight gain (19%) and serum triglycerides (37%) in HFFD-fed rats. These benefits were related to a greater lipid excretion in feces (97%) and the partial inhibition of pancreatic lipase in vitro by the aqueous extract and the hydrolyzed proteins obtained from AD. Additionally, the 8% AD supplementation improved insulin resistance measured by the HOMA index (61%). Thus, 8% AD supplementation to HFFD-fed rats was effective in preventing obesity, dyslipidemia, and insulin resistance. PRACTICAL APPLICATIONS: Obesity is a risk factor for developing insulin resistance and dyslipidemia. Therefore, there is an increasing interest in consuming foods rich in bioactive compounds as therapeutic alternatives for managing the development of obesity and its complications. Edible insects, such as crickets, are attractive for treating obesity due to their content of protein, fiber, and polyunsaturated fatty acids. Studies have explored the effect of glycosaminoglycan (GAG)-enriched extracts from the cricket Gryllus bimaculatus against obesity. However, GAG content in crickets is low, and crickets are commonly consumed whole instead of extracts. The cricket Acheta domesticus (AD) is among the most rearing cricket species as it is easy to farm and has a better flavor. However, limited studies have explored the beneficial effects of AD consumption. This study demonstrates that AD prevents obesity and ameliorates dyslipidemia and insulin resistance. Therefore, AD is a valuable entomotherapeutic strategy to reduce the comorbidities associated with diet-induced obesity.

Avocado oil alleviates non-alcoholic fatty liver disease by improving mitochondrial function, oxidative stress and inflammation in rats fed a high fat-High fructose diet.

Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in hepatocytes, and in advanced stages, by inflammation and fibrosis. Excessive ROS production due to mitochondrial dysfunction contributes to NAFLD development, making the decrease in mitochondrial ROS production an emerging target to alleviate NAFLD. Previously, we have shown that avocado oil, a source of several bioactive compounds with antioxidant effects, decreases oxidative stress by improving the function of the mitochondrial electron transport chain (ETC) and decreasing ROS levels in mitochondria of diabetic and hypertensive rats. Therefore, we tested in this work whether avocado oil alleviates NAFLD by attenuating mitochondrial dysfunction, oxidative stress and inflammation. NAFLD was induced in rats by a high fat-high fructose (HF) diet administered for six (HF6) or twelve (HF12) weeks. Hepatic steatosis, hypertrophy and inflammation were detected in both the HF6 and HF12 groups. Hyperglycemia was observed only in the HF12 group. The HF6 and HF12 groups displayed dyslipidemia, impairments in mitochondrial respiration, complex III activity, and electron transfer in cytochromes in the complex III. This led to an increase in the levels of ROS and lipid peroxidation. The substitution of the HF6 diet by standard chow and avocado oil for 6 weeks (HF6+AVO + D), or supplementation of the HF12 diet with avocado oil (HF12 + AVO), ameliorated NAFLD, hyperglycemia, dyslipidemia, and counteracted mitochondrial dysfunctions and oxidative stress. The substitution of the HF6 diet by standard chow without avocado oil did not correct many of these abnormalities, confirming that the removal of the HF diet is not enough to counteract NAFLD and mitochondrial dysfunction. In summary, avocado oil decreases NAFLD by improving mitochondrial function, oxidative stress, and inflammation.

Chemical and sensorial characterization of Tejate, a Mexican traditional maize-cocoa beverage, and improvement of its nutritional value by protein addition.

Tejate is a Mexican traditional beverage elaborated with nixtamalized maize (Zea mays L.), cocoa (Theobroma cacao L.) beans, cacao flowers (Quararibea funebris), and mamey sapota fruit seeds (Pouteria sapota) that is considered a refreshing drink with satiety properties. Local formulations show a high content of minerals, but a relatively low protein content. The aim of this study was to identify a standardarized formulation but conserving physicochemical and sensorial ethnic identity of traditional Tejate, and to improve its nutritional value with the addition of protein without modifying its sensorial profile. A 24-1 fractional factorial design with central point was used to vary ingredients concentration and the amount of ash used for maize nixtamalization instead of lime (calcium hydroxide) was 75 g/100 g (w/w) of wood ashes in 2 L water. The standardized traditional formulation (TF) was selected through a sensory analysis with an expert panel: 20 g of cacao flowers, 30 g of mamey sapota fruit seeds, and 100 g of cocoa beans per kg of maize nixtamalized with 6% of ash. Whey protein concentrate (80% of protein) or soy protein isolate (88% of protein) were added to the TF at 1, 2, and 2.5%. The addition of 1% soy protein isolate increased TF protein content without modifying its physicochemical parameters, and improved the beverage stability during cold storage. The protein-rich Tejate formulation could be used as a functional beverage maintaining its ethnic identity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05073-w.

Citrus decoction by-product represents a rich source of carotenoid, phytosterol, extractable and non-extractable polyphenols.

This study aimed to carry out an exhaustive chemical characterization of citrus (orange, mandarin, and grapefruit) decoctions as well as the residues obtained during the decoction process (by-products). The citrus decoctions were rich in hesperidin, naringin, and narirutin, but carotenoids and phytosterols were not detected. Interestingly, these flavanones were found in a higher concentration in the extractable polyphenol fraction of the citrus decoction by-products. Moreover, the greatest content of hesperidin and naringin was found bound to the food matrix by ether/ester bonds. Violaxanthin and ß-cryptoxanthin were found as major carotenoids in the orange and mandarin decoction by-products, respectively, whereas the grapefruit decoction by-product showed a low content of carotenoids. All citrus by-products showed ß-sitosterol as the major phytosterol, followed by ß-campesterol. Therefore, the by-products obtained during the elaboration of citrus decoctions are rich sources of bioactive compounds that can be used for the development of functional foods or dietary supplements.

Chemopreventive Effect of the Germinated Oat and its Phenolic-AVA Extract in Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) Model of Colon Carcinogenesis in Mice.

The consumption of fruits, vegetables, nuts, legumes, and whole grains has been associated with a lower risk of colorectal cancer (CRC) due to the content of natural compounds with antioxidant and anticancer activities. The oat (Avena sativa L.) is a unique source of avenanthramides (AVAs), among other compounds, with chemopreventive effects. In addition, oat germination has shown enhanced nutraceutical and phytochemical properties. Therefore, our objective was to evaluate the chemopreventive effect of the sprouted oat (SO) and its phenolic-AVA extract (AVA) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model. Turquesa oat seeds were germinated (five days at 25 °C and 60% relative humidity) and, after 16 weeks of administration, animals in the SO- and AVA-treated groups had a significantly lower inflammation grade and tumor (38-50%) and adenocarcinoma (38-63%) incidence compared to those of the AOM+DSS group (80%). Although both treatments normalized colonic GST and NQO1 activities as well as erythrocyte GSH levels, and significantly reduced cecal and colonic ß-GA, thus indicating an improvement in the intestinal parameters, the inflammatory states, and the redox states of the animals, SO exerted a superior chemopreventive effect, probably due to the synergistic effects of multiple compounds. Our results indicate that oats retain their biological properties even after the germination process.

Oral Administration of Microencapsulated B. Longum BAA-999 and Lycopene Modulates IGF-1/IGF-1R/IGFBP3 Protein Expressions in a Colorectal Murine Model.

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13-38%) and adenocarcinoma (13-14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and ß-glucuronidase (ß-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.

Chemical characterization, antioxidant and antimutagenic evaluations of pigmented corn.

In order to identify pigmented corn with nutraceutical potential, the secondary metabolite content, the antioxidant capacity and antimutagenic activity of red, and blue corn were analyzed. The ranges of total phenolic, flavonoid and anthocyanin contents of the corn samples were from 69.4 to 212.8 mg gallic ac. equiv./100 g DW, 0.07 to 12.19 mg (+) catechin eq./100 g DW and 3.89 to 34.17 mg cyanidin-3-O-glucoside eq./100 g DW, respectively. The phenolic extracts demonstrated the highest antioxidant capacity evaluated by the ABTS assay displaying values from 2.06 to 7.34 mmol Trolox/100 g DW. None of the extracts was toxic to the tested bacteria strains TA98 and TA100. For TA98 tester strain, percentage inhibition values against AFB1 mutagenicity from 61 to 93, and 38 to 75 for flavonoid and anthocyanin extracts were obtained. The total phenol and anthocyanin contents correlate with the observed antioxidant capacity. The most biological active corn samples were the blue color while the least actives were the red ones. The results show that the studied blue corn samples are good sources of antioxidant and antimutagenic compounds, which could use to develop products that contribute to human health.

Resveratrol induces mitochondrial dysfunction and decreases chronological life span of Saccharomyces cerevisiae in a glucose-dependent manner.

A broad range of health benefits have been attributed to resveratrol (RSV) supplementation in mammalian systems, including the increases in longevity. Nonetheless, despite the growing number of studies performed with RSV, the molecular mechanism by which it acts still remains unknown. Recently, it has been proposed that inhibition of the oxidative phosphorylation activity is the principal mechanism of RSV action. This mechanism suggests that RSV might induce mitochondrial dysfunction resulting in oxidative damage to cells with a concomitant decrease of cell viability and cellular life span. To prove this hypothesis, the chronological life span (CLS) of Saccharomyces cerevisiae was studied as it is accepted as an important model of oxidative damage and aging. In addition, oxygen consumption, mitochondrial membrane potential, and hydrogen peroxide (H2O2) release were measured in order to determine the extent of mitochondrial dysfunction. The results demonstrated that the supplementation of S. cerevisiae cultures with 100 µM RSV decreased CLS in a glucose-dependent manner. At high-level glucose, RSV supplementation increased oxygen consumption during the exponential phase yeast cultures, but inhibited it in chronologically aged yeast cultures. However, at low-level glucose, oxygen consumption was inhibited in yeast cultures in the exponential phase as well as in chronologically aged cultures. Furthermore, RSV supplementation promoted the polarization of the mitochondrial membrane in both cultures. Finally, RSV decreased the release of H2O2 with high-level glucose and increased it at low-level glucose. Altogether, this data supports the hypothesis that RSV supplementation decreases CLS as a result of mitochondrial dysfunction and this phenotype occurs in a glucose-dependent manner.

Lycopene Improves Diet-Mediated Recuperation in Rat Model of Nonalcoholic Fatty Liver Disease.

The aim of the present study was to evaluate the synergic effect of lycopene (LYC) treatment with a dietary control in a nonalcoholic fatty liver disease (NAFLD) model induced with a high-fat diet (HFD). Sprague-Dawley rats were fed during 4 weeks with a normal diet (ND·4w) or an HFD (HFD·4w) to produce an NAFLD model. Then, rats from the ND·4w group continued during 4 weeks with the same diet (ND·8w), and rats from HFD were fed during 4 weeks with an ND (HFD·4w+ND·4w) or an ND plus LYC (HFD·4w+ND+LYC·4w). LYC (20 mg/kg) was administered daily by gavage. ND and ND+LYC diets partially reverted the following alterations due to HFD: liver weight, serum low-density lipoproteins (LDL), hepatic total cholesterol (TC), and catalytic activity of hepatic superoxide dismutase, catalase, and glutathione peroxidase, as well as macroscopic and microscopic images of livers. A higher recuperation to reach normality was obtained with ND+LYC in: liver weight, hepatic TC, serum LDL, and, in some instances, macroscopic and microscopic images of livers. Failures to recovery with both NDs were observed for malondialdehyde level and serum aspartate aminotransferase activity. Taken together, the results from this study suggest the potentially protective role of LYC against NAFLD; however, more clinical trials are needed to support this idea.

Energy-dependent effects of resveratrol in Saccharomyces cerevisiae.

The metabolic effects induced by resveratrol have been associated mainly with the consumption of high-calorie diets; however, its effects with standard or low-calorie diets remain unclear. To better understand the interactions between resveratrol and cellular energy levels, we used Saccharomyces cerevisiae as a model. Herein it is shown that resveratrol: (a) decreased cell viability in an energy-dependent manner; (b) lessening of cell viability occurred specifically when cells were under cellular respiration; and (c) inhibition of oxygen consumption in state 4 occurred at low and standard energy levels, whereas at high energy levels oxygen consumption was promoted. These findings indicate that the effects of resveratrol are dependent on the cellular energy status and linked to metabolic respiration. Importantly, our study also revealed that S. cerevisiae is a suitable and useful model to elucidate the molecular targets of resveratrol under different nutritional statuses. Copyright © 2016 John Wiley & Sons, Ltd.

Resveratrol Inhibition of Cellular Respiration: New Paradigm for an Old Mechanism.

Resveratrol (3,4',5-trihydroxy-trans-stilbene, RSV) has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits exerted in mammals. Nonetheless, early studies have also demonstrated its toxic properties toward plant-pathogenic fungi of this phytochemical. Both effects appear to be opposed and caused by different molecular mechanisms. However, the inhibition of cellular respiration is a hypothesis that might explain both toxic and beneficial properties of resveratrol, since this phytochemical: (1) decreases the production of energy of plant-pathogenic organisms, which prevents their proliferation; (2) increases adenosine monophosphate/adenosine diphosphate (AMP/ADP) ratio that can lead to AMP protein kinase (AMPK) activation, which is related to its health effects, and (3) increases the reactive oxygen species generation by the inhibition of electron transport. This pro-oxidant effect induces expression of antioxidant enzymes as a mechanism to counteract oxidative stress. In this review, evidence is discussed that supports the hypothesis that cellular respiration is the main target of resveratrol.

Resveratrol increases glycolytic flux in Saccharomyces cerevisiae via a SNF1-dependet mechanism.

Evidence suggests that AMP protein kinase (AMPK) is the main target of the phytochemical resveratrol (RSV) in mammalian cells. Data also indicates that RSV stimulates glucose metabolism; however, the molecular link between RSV and glucose uptake remains unknown. Herein, we provide evidence indicating that RSV stimulates glycolysis via sucrose non-fermenting 1 gene (SNF1, Saccharomyces cerevisiae orthologous of AMPK). S. cerevisiae cultures treated with 30 µM RSV showed an increase in extracellular acidification rate compared to untreated cells, indicating an elevated glycolytic flux. Also, RSV treatment increased transcription levels of two key glycolytic genes, hexokinase 2 (HXK2) and phosphofructokinase 1 (PFK1), as well as production of NADH. Moreover, RSV treatment inhibited mitochondrial respiration when glucose was used as a carbon source. Importantly, the effects of RSV on glycolysis were dependent of SNF1. Taken together, these findings suggest that SNF1 (AMPK in mammalian systems) is the molecular target of RSV in S. cerevisiae.