Body weight gain and control: beneficial effect of extra virgin olive oil versus corn oil in an experimental model of mammary cancer.

Obesity is a known risk factor for breast cancer, the most common malignancy among women worldwide. We have previously described different effects of high-fat diets on mammary experimental carcinogenesis. In this work, we analyzed the animal growth data obtained in six experimental assays, in healthy and carcinogen-induced rats undergoing different dietary interventions. The animals were fed with three experimental diets administered at different periods of development: a control low-fat diet, and two isocaloric high-fat diets (rich in corn oil or in extravirgin olive oil -EVOO-). Weekly weight throughout the development of 818 animals have been compiled and reanalyzed using adjusted mathematical models. Molecular mechanisms have been investigated: ethanolamides in small intestine, neuropeptides controlling satiety in hypothalamus, and proteins controlling lipid metabolism in adipose and mammary tissues. The results indicated that the effect of diets depended on type of lipid, timing of intervention and health status. The high corn oil diet, but not the high EVOO diet, increased body weight and mass, especially if administered from weaning, in healthy animals and in those that received a moderate dose of carcinogen. The potential protective effect of EVOO on weight maintenance may be related to anorexigenic neuropeptides such as oxytocin and lipolysis/deposition balance in adipose tissue (increasing phospho-PKA, HSL, MGL and decreasing FAS). In animals with cancer, body weight gain was related to the severity of the disease. Taken together, our results suggest that EVOO has a beneficial effect on body weight maintenance in both health and cancer.

Effects of a Calorie-Restricted Cafeteria Diet and Oleuropein Supplementation on Adiposity and mRNA Expression of Energy Balance Related Genes in Obese Male Rats.

Supplementation with natural bioactive compounds has been proposed to be a complementary tool to the calorie-restricted diets and physical exercise programs used to tackle human overweight, obesity and Metabolic syndrome. Herein, we evaluated the effects of 14 weeks of calorie-restricted cafeteria diet either alone or combined with oral administration of the polyphenol oleuropein in obese adult male rats, compared with a control group fed standard chow and a group fed cafeteria diet. Animals were sacrificed at the age of 26 weeks and several tissues of interest were removed. The results showed that both dietary interventions reduced the adiposity index (p < 0.05 and p < 0.01, respectively), and specifically the abdominal fat depots (mesenteric: p < 0.01 and p < 0.01, respectively; and epididymal: both diets p < 0.001) and restored the decreased soleus skeletal muscle mass. Both interventions decreased leptin mRNA expression in mesenteric white adipose tissue (p < 0.05) and normalized hypothalamic Agrp mRNA expression compared to cafeteria-fed obese rats (p < 0.05). However, only the calorie-restricted cafeteria diet supplemented with oleuropein induced additional lower retroperitoneal adipose accretion (p < 0.05) and increased hypothalamic leptin receptor mRNA levels (p < 0.05). Experiments with female animals, at different doses and longer intervention periods, are needed to better determine the potential benefits of this dietary treatment.

Ultra-Processed Foods and Drinks Consumption Is Associated with Psychosocial Functioning in Adolescents.

Adolescents show one of the highest rates of ultra-processed foods and drinks (UPF) consumption, and studies indicate an association between their consumption and internalizing problems. We aim to investigate whether UPF consumption associates with dysfunctions in other psychosocial domains, as well as sex effects. In 560 Spanish adolescents (14-17 years old), we assessed the UPF products consumed in the previous day, fruits and vegetables consumption (servings/day), and physical activity (days/week). Psychosocial functioning (total and subscales) was assessed through the Pediatric Symptom Checklist-Youth self-report. Associations between UPF and psychosocial functioning were assessed using linear regression models, adjusting for sex, age, fruits and vegetables consumption, and physical activity. Sex-specific associations were also explored. Participants reported a daily consumption of 7.72 UPF servings per day, with male adolescents showing higher consumption than female adolescents. Consumption of fruits and vegetables and physical activity levels were lower than recommended. Psychosocial impairment was present in 26.2% of the participants. Higher UPF consumption was associated with higher presence of depressive symptoms and internalizing and externalizing problems in the whole sample and in male adolescents. The present study supports previous studies suggesting that UPF consumption may interact with mental health problems and indicates that these effects may go beyond internalizing problems.

Restricted cafeteria feeding and treadmill exercise improved body composition, metabolic profile and exploratory behavior in obese male rats.

The aim of this study was to evaluate, in male Long-Evans rats, whether a restricted-cafeteria diet (CAFR), based on a 30% calorie restriction vs continuous ad libitum cafeteria (CAF) fed animals, administered alone or in combination with moderate treadmill exercise (12 m/min, 35 min, 5 days/week for 8 weeks), was able to ameliorate obesity and the associated risk factors induced by CAF feeding for 18 weeks and to examine the changes in circadian locomotor activity, hypothalamic-pituitary-adrenal (HPA) axis functionality, and stress response elicited by this dietary pattern. In addition to the expected increase in body weight and adiposity, and the development of metabolic dysregulations compatible with Metabolic Syndrome, CAF intake resulted in a sedentary profile assessed by the home-cage activity test, reduced baseline HPA axis activity through decreased corticosterone levels, and boosted exploratory behavior. Both CAFR alone and in combination with exercise reduced abdominal adiposity and hypercholesterolemia compared to CAF. Exercise increased baseline locomotor activity in the home-cage in all dietary groups, boosted exploratory behavior in STD and CAF, partially decreased anxiety-like behavior in CAF and CAFR, but did not affect HPA axis-related parameters.

Dissecting ultra-processed foods and drinks: Do they have a potential to impact the brain?

Ultra-processed foods and drinks (UPF) are formulation of ingredients, mostly of exclusive industrial use, that result from a series of industrial processes. They usually have a low nutrient but high energy density, with a high content of saturated and trans fats, and added sugars. In addition, they have characteristic organoleptic properties, and usually contain sophisticated additives, including artificial sweeteners, to intensify their sensory qualities and imitate the appearance of minimally processed foods. In addition, recent research has warned about the presence of chemicals (e.g., bisphenol) and neo-formed contaminants in these products. UPF production and consumption growth have been spectacular in the last decades, being specially consumed in children and adolescents. UPF features have been associated with a range of adverse health effects such as overeating, the promotion of inflammatory and oxidative stress processes, gut dysbiosis, and metabolic dysfunction including problems in glucose regulation. The evidence that these UPF-related adverse health effects may have on the neural network implicated in eating behavior are discussed, including the potential impact on serotonergic and dopaminergic neurotransmission, brain integrity and function. We end this review by placing UPF in the context of current food environments, by suggesting that an increased exposure to these products through different channels, such as marketing, may contribute to the automatic recruitment of the brain regions associated with food consumption and choice, with a detrimental effect on inhibitory-related prefrontal cortices. While further research is essential, preliminary evidence point to UPF consumption as a potential detrimental factor for brain health and eating behavior.

Impact of Calorie-Restricted Cafeteria Diet and Treadmill Exercise on Sweet Taste in Diet-Induced Obese Female and Male Rats.

The goal of the present study was to evaluate the sweet taste function in obese rats fed with a 30% calorie-restricted cafeteria diet (CAFR) and/or subjected to moderate treadmill exercise (12-17 m/min, 35 min, 5 days per week) for 9 weeks. A two-bottle preference test, a taste reactivity test, and a brief-access licking test were carried out when animals were aged 21 weeks; biometric and metabolic parameters were also measured along the interventions. Two separate experiments for females and males were performed. Behaviorally, CAF diet decreased sucrose intake and preference, as well as perceived palatability, in both sexes and decreased hedonic responses in males. Compared to the CAF diet, CAFR exerted a corrective effect on sweet taste variables in females by increasing sucrose intake in the preference test and licking responses, while exercise decreased sucrose intake in both sexes and licking responses in females. As expected, CAF diet increased body weight and Lee index and worsened the metabolic profile in both sexes, whereas CAFR diet ameliorated these effects mainly in females. Exercise had no noticeable effects on these parameters. We conclude that CAF diet might diminish appetitive behavior toward sucrose in both sexes, and that this effect could be partially reverted by CAFR diet in females only, while exercise might exert protective effects against overconsumption of sucrose in both sexes.

Behavioral and Metabolic Effects of a Calorie-Restricted Cafeteria Diet and Oleuropein Supplementation in Obese Male Rats.

Diet-induced obesity models are widely used to investigate dietary interventions for treating obesity. This study was aimed to test whether a dietary intervention based on a calorie-restricted cafeteria diet (CAF-R) and a polyphenolic compound (Oleuropein, OLE) supplementation modified sucrose intake, preference, and taste reactivity in cafeteria diet (CAF)-induced obese rats. CAF diet consists of high-energy, highly palatable human foods. Male rats fed standard chow (STD) or CAF diet were compared with obese rats fed CAF-R diet, alone or supplemented with an olive tree leaves extract (25 mg/kg*day) containing a 20.1% of OLE (CAF-RO). Biometric, food consumption, and serum parameters were measured. CAF diet increased body weight, food and energy consumption and obesity-associated metabolic parameters. CAF-R and CAF-RO diets significantly attenuated body weight gain and BMI, diminished food and energy intake and improved biochemical parameters such as triacylglycerides and insulin resistance which did not differ between CAF-RO and STD groups. The three cafeteria groups diminished sucrose intake and preference compared to STD group. CAF-RO also diminished the hedonic responses for the high sucrose concentrations compared with the other groups. These results indicate that CAF-R diet may be an efficient strategy to restore obesity-associated alterations, whilst OLE supplementation seems to have an additional beneficial effect on sweet taste function.

A restricted cafeteria diet ameliorates biometric and metabolic profile in a rat diet-induced obesity model.

The administration of anti-obesity bioactive compounds and/or functional foods in rodents fed energy restriction diets based on chow food can be difficult to interpret. We propose an energy restricted cafeteria (CAF) diet as a dietetic intervention to be combined with other therapies. Postweaning male rats were fed standard chow, CAF diet or 30% energy restricted CAF diet (CAF-R) for 8 weeks. The CAF-R diet lowered energy intake and the increase of body weight and body mass index due to the CAF diet, lead to an intermediate feed efficiency, and dampened the CAF diet-induced alterations on body composition, serum levels of triacylglycerides and NEFAs, and insulin resistance. These effects were associated with diminished Ucp1, Nrf1 and Tfam1 gene expression in brown adipose tissue. In conclusion, the CAF-R diet ameliorated obesity and related metabolic disorders induced by a regular CAF diet, turning it in a useful tool to study anti-obesity compounds.

Effects of diets high in corn oil or in extra virgin olive oil on oxidative stress in an experimental model of breast cancer.

Experimental evidence highlights the importance of dietetic factors on breast cancer. In this work we aimed to analyze the effects two oils, corn oil (rich in n-6 polyunsaturated fatty acids -PUFA-) and extra virgin olive oil (EVOO), on oxidative stress in an animal model of breast carcinogenesis. Female rats were fed a low-fat control, a high-corn oil, or a high-EVOO diet from weaning or after induction with 7,12-dimethylbenz[a]anthracene at 53 days. Animals were euthanized at 36, 51, 100 and 246 days of age. We analyzed antioxidant enzymes (mRNA and activity of superoxide dismutase, glutathione peroxidase and catalase), non-enzymatic capacity (oxidized and reduced glutathione) and DNA damage (8-oxo-dG) in tumors and mammary gland at different ages. We also analyzed lipid peroxidation (isoprostanes in serum and lipofuscin in liver). Results indicated a decrease in the enzymatic antioxidant capacity and increased oxidative stress in mammary gland of healthy young animals after a short period of high-fat diets intake, followed by an adaptation to chronic dietary intervention. After induction both diets, especially the one high in n-6 PUFA, increased the oxidized glutathione. In tumors no clear effects of the high-fat diets were observed, although in the long-term lipofuscin and 8-oxo-dG suggested greater oxidative damage by effect of the n-6 PUFA-rich diet. Considering the differential effects of these diets on mammary carcinogenesis that we have previously reported, this study suggests that these high-fat diets could have an effect on oxidative stress that would lead to different signaling pathways.

Dietary lipids differentially modulate the initiation of experimental breast carcinogenesis through their influence on hepatic xenobiotic metabolism and DNA damage in the mammary gland.

Breast cancer is the most common malignancy among women worldwide. In addition to reproductive factors, environmental factors such as nutrition and xenobiotic exposure have a role in the etiology of this malignancy. A stimulating and a potentially protective effect on experimental breast cancer has been previously described for high corn oil and high extra-virgin olive oil diets, respectively. This work investigates the effect of these lipids on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon that can initiate carcinogenesis and its consequences in an experimental rat breast cancer model. The PUFA n-6-enriched diet increased expression of Phase I enzymes prior to DMBA administration and raised the activity of CYP1s in the hours immediately after induction, while reducing the activity of Phase II enzymes, mainly NQO1. The levels of reactive metabolites measured in plasma by GC-MS and DMBA-DNA adducts in the mammary gland of the animals fed the high corn oil diet were also higher than in the other groups. On the other hand, the high extra-virgin olive oil diet and the control low-fat diet exhibited better coordinated Phase I and Phase II activity, with a lower production of reactive metabolites and less DNA damage in the mammary gland. The concordance between these effects and the different efficacy of the carcinogenesis process due to the dietary treatment suggest that lipids may differently modify mammary gland susceptibility or resistance to cancer initiation over the exposure to environmental carcinogens. SUMMARY: Dietary lipids influence the initiation of DMBA-induced mammary cancer through the modulation of liver xenobiotic metabolism, formation of reactive metabolites and subsequent DNA damage in the target tissue.

Diets high in corn oil or extra-virgin olive oil differentially modify the gene expression profile of the mammary gland and influence experimental breast cancer susceptibility.

PURPOSE: Nutritional factors, especially dietary lipids, may have a role in the etiology of breast cancer. We aimed to analyze the effects of high-fat diets on the susceptibility of the mammary gland to experimental malignant transformation. METHODS: Female Sprague-Dawley rats were fed a low-fat, high-corn-oil, or high-extra-virgin olive oil (EVOO) diet from weaning or from induction. Animals were induced with 7,12-dimethylbenz[a]anthracene at 53 days and euthanized at 36, 51, 100 and 246 days. Gene expression profiles of mammary glands were determined by microarrays. Further molecular analyses were performed by real-time PCR, TUNEL and immunohistochemistry. Carcinogenesis parameters were determined at 105 and 246 days. RESULTS: High-corn-oil diet increased body weight and mass when administered from weaning. The EVOO diet did not modify these parameters and increased the hepatic expression of UCP2, suggesting a decrease in intake/expenditure balance. Both diets differentially modified the gene expression profile of the mammary gland, especially after short dietary intervention. Corn oil down-regulated the expression of genes related to immune system and apoptosis, whereas EVOO modified the expression of metabolism genes. Further analysis suggested an increase in proliferation and lower apoptosis in the mammary glands by effect of the high-corn-oil diet, which may be one of the mechanisms of its clear stimulating effect on carcinogenesis. CONCLUSIONS: The high-corn-oil diet strongly stimulates mammary tumorigenesis in association with modifications in the expression profile and an increased proliferation/apoptosis balance of the mammary gland.

The Role of Dietary Extra Virgin Olive Oil and Corn Oil on the Alteration of Epigenetic Patterns in the Rat DMBA-Induced Breast Cancer Model.

Disruption of epigenetic patterns is a major change occurring in all types of cancers. Such alterations are characterized by global DNA hypomethylation, gene-promoter hypermethylation and aberrant histone modifications, and may be modified by environment. Nutritional factors, and especially dietary lipids, have a role in the etiology of breast cancer. Thus, we aimed to analyze the influence of different high fat diets on DNA methylation and histone modifications in the rat dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. Female Sprague-Dawley rats were fed a low-fat, a high corn-oil or a high extra-virgin olive oil (EVOO) diet from weaning or from induction with DMBA. In mammary glands and tumors we analyzed global and gene specific (RASSF1A, TIMP3) DNA methylation by LUMA and bisulfite pyrosequencing assays, respectively. We also determined gene expression and enzymatic activity of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) and evaluated changes in histone modifications (H3K4me2, H3K27me3, H4K20me3 and H4K16ac) by western-blot. Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging. The olive oil-enriched diet, on the one hand, increased the levels of global DNA methylation in mammary gland and tumor, and on the other, changed histone modifications patterns. The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3. These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

[CONSENSUS ON FATS AND OILS IN THE DIET OF S ISH ADULTS; POSITION PAPER OF THE SPANISH FEDERATION OF FOOD, NUTRITION AND DIETETICS SOCIETIES]. / CONSENSO SOBRE LAS GRASAS Y ACEITES EN LA ALIMENTACIÓN DE LA POBLACIÓN ESPAÑOLA ADULTA; POSTURA DE LA FEDERACIÓN ESPAÑOLA DE SOCIEDADES DE ALIMENTACIÓN, NUTRICIÓN Y DIETÉTICA (FESNAD).

The quality of dietary fat critically influences health. In this consensus document the scientific evidence relating effects of dietary fat quantity and quality on cardiovascular risk is reviewed and recommendations for the Spanish adult population are issued. As a novelty in nutrition guidelines, emphasis is made more on parent foods than on fatty acids per se. In summary, replacing saturated fatty acids (SFA) for monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) reduces cardiovascular risk. Recent data suggest that SFA proper may be harmful or not depending on the parent food, a reason why an intake threshold is not established, but consumption of foods containing excess SFA, such as butter, some processed meats, and commercial confectionery and fried foods is discouraged. The established threshold of <1 % of energy intake as trans FA, well known to be harmful for cardiovascular risk, is fulfilled in Spain due in part to its present low levels in margarines. MUFA are beneficial or neutral for cardiovascular risk depending on their dietary sources (virgin olive oil versus other fats), and no intake limitations are established.n-6 PUFA are cardioprotective and recommended intakes (5-10 % of energy) are not always fulfilled in the Spanish population, thus increased consumption of their vegetable food sources (seeds, derived oils, and margarines)is encouraged. Marine n-3 PUFA are also cardioprotective and the recommendation stands to eat fatty fish≥2 servings/weeks to reach intake levels of at least 250 mg/day. Increasing evidence suggests that alpha-linolenic acid (ALA), the vegetable n-3 PUFA, is also cardioprotective,but the parent foods (walnuts, soy products,green-leaf vegetables) may provide benefits beyond ALA itself. Finally, low-fat (high carbohydrate, particularly when having a high glycemic index) diets appear to lack cardiovascular preventive effects, while high-fat,high-vegetable fat dietary patterns such as the Mediterranean diet, are protective, a reason why no upper limit on fat intake is established for the Spanish population.This position statement targets dietitians, nutritionists and other health professionals involved in dietary counsel so they can deliver it rightly and according to the last scientific evidence.

La calidad de la grasa dietética tiene una profunda influencia sobre la salud. En este documento de consenso se evalúa la evidencia científica relativa a los efectos de la cantidad y calidad de la grasa alimentaria sobre la salud cardiovascular y se emiten recomendaciones para la población española adulta. Como novedad en unas guías nutricionales, se hace menos hincapié en los ácidos grasos per se que en los alimentos que los contienen. En resumen, sustituir ácidos grasos saturados (AGS) por monoinsaturados (AGM) y poliinsaturados (AGP) reduce el riesgo cardiovascular. Datos recientes sugieren que la ingesta de AGS per se es nociva solo en función del alimento que los contiene, por lo que no parece oportuno establecer un umbral de ingesta, pero se desaconsejan alimentos que los contienen en exceso, como la mantequilla y algunos derivados cárnicos, bollería y fritos comerciales. El límite de.

Consenso sobre las grasas y aceites en la alimentación de la población española adulta; postura de la Federación Española de Sociedades de Alimentación, Nutrición y Dietética (FESNAD) / Consensus on fats and oils in the diet of spanish adults; position paper of the spanish federation of food, nutrition and dietetics societies

La calidad de la grasa dietética tiene una profunda influencia sobre la salud. En este documento de consenso se evalúa la evidencia científica relativa a los efectos de la cantidad y calidad de la grasa alimentaria sobre la salud cardiovascular y se emiten recomendaciones para la población española adulta. Como novedad en unas guías nutricionales, se hace menos hincapié en los ácidos grasos per se que en los alimentos que los contienen. En resumen, sustituir ácidos grasos saturados (AGS) por monoinsaturados (AGM) y poliinsaturados (AGP) reduce el riesgo cardiovascular. Datos recientes sugieren que la ingesta de AGS per se es nociva solo en función del alimento que los contiene, por lo que no parece oportuno establecer un umbral de ingesta, pero se desaconsejan alimentos que los contienen en exceso, como la mantequilla y algunos derivados cárnicos, bollería y fritos comerciales. El límite de su bajo nivel actual en las margarinas. Los AGM son beneficiosos o neutros para el riesgo cardiovascular según su fuente dietética (aceite de oliva virgen frente a otras grasas), y no se establecen limitaciones de ingesta. Los AGP n-6 son cardioprotectores y el nivel recomendable de ingesta (5-10 % de la energía) no siempre se cumple en la población española, que debería aumentar el consumo de sus fuentes vegetales (semillas, aceites derivados y margarinas). Los AGP n-3 de origen marino son cardioprotectores y se recomienda consumir pescado graso ≥2 veces/semana para cumplir con la recomendación de al menos 250 mg/día. Existen evidencias crecientes de que el ácido alfa-linolénico (ALA), el AGP n-3 de origen vegetal, también es cardioprotector, pero los alimentos que lo contienen (nueces, soja, vegetales de hoja verde) pueden ser beneficiosos más allá del propio ALA. Finalmente, las dietas bajas en grasa (altas en hidratos de carbono, particularmente aquellas con un alto índice glicémico) carecen de efecto preventivo cardiovascular, mientras que las altas en grasa de origen vegetal, como la dieta mediterránea, son protectoras, razón por la que en España no parece necesario establecer un dintel superior de ingesta de grasa. Este documento de consenso se dirige a dietistas, nutricionistas y otros profesionales que dan consejo dietético para que puedan hacerlo de una manera razonada y acorde con la última evidencia científica (AU)

The quality of dietary fat critically influences health. In this consensus document the scientific evidence relating effects of dietary fat quantity and quality on cardiovascular risk is reviewed and recommendations for the Spanish adult population are issued. As a novelty in nutrition guidelines, emphasis is made more on parent foods than on fatty acids per se. In summary, replacing saturated fatty acids (SFA) for monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) reduces cardiovascular risk. Recent data suggest that SFA proper may be harmful or not depending on the parent food, a reason why an intake threshold is not established, but consumption of foods containing excess SFA, such as butter, some processed meats, and commercial confectionery and fried foods is discouraged. The established threshold of known to be harmful for cardiovascular risk, is fulfilled in Spain due in part to its present low levels in margarines. MUFA are beneficial or neutral for cardiovascular risk depending on their dietary sources (virgin olive oil versus other fats), and no intake limitations are established. n-6 PUFA are cardioprotective and recommended intakes (5-10 % of energy) are not always fulfilled in the Spanish population, thus increased consumption of their vegetable food sources (seeds, derived oils, and margarines) is encouraged. Marine n-3 PUFA are also cardioprotective and the recommendation stands to eat fatty fish ≥2 servings/weeks to reach intake levels of at least 250 mg/day. Increasing evidence suggests that alpha-linolenic acid (ALA), the vegetable n-3 PUFA, is also cardioprotective, but the parent foods (walnuts, soy products, green-leaf vegetables) may provide benefits beyond ALA itself. Finally, low-fat (high carbohydrate, particularly when having a high glycemic index) diets appear to lack cardiovascular preventive effects, while high-fat, high-vegetable fat dietary patterns such as the Mediterranean diet, are protective, a reason why no upper limit on fat intake is established for the Spanish population. This position statement targets dietitians, nutritionists and other health professionals involved in dietary counsel so they can deliver it rightly and according to the last scientific evidence (AU)

Effect of High Fat Diets on Body Mass, Oleylethanolamide Plasma Levels and Oxytocin Expression in Growing Rats.

Obesity prevalence in developed countries has promoted the need to identify the mechanisms involved in control of feeding and energy balance. We have tested the hypothesis that different fats present in diet composition may contribute in body weight gain and body indexes by regulation of oxytocin gene (oxt) expression in hypothalamus and Oleylethanolamide (OEA) levels in plasma. Sprague-Dawley rats were fed two high fat diets, based on corn (HCO) and extra virgin olive oil (HOO) and results were compared to a low fat diet (LF). LC-MS/MS analysis showed an increasing trend of OEA plasma levels in HOO group, although no significant differences were found. However, body weight gain of LF and HOO were similar and significantly lower than HCO. HCO rats also had higher Lee index than HOO. Rats fed HOO diet showed higher levels of hypothalamic oxt mRNA expression, which could indicate that oxytocin may be modulated by dietary lipids.

Dietary extra-virgin olive oil and corn oil differentially modulate the mRNA expression of xenobiotic-metabolizing enzymes in the liver and in the mammary gland in a rat chemically induced breast cancer model.

High extra-virgin olive oil (EVOO) and corn oil diets differentially modulate experimental mammary carcinogenesis. We have investigated their influence on the initiation stage through the modulation of the expression of xenobiotic-metabolizing enzymes (XMEs) in the liver and the mammary gland. Female Sprague-Dawley rats were fed a low-fat (LF), high corn oil (HCO), or high EVOO (HOO) diet from weaning and gavaged with 7,12-dimethylbenz(a)anthracene (DMBA). The HCO diet increased the mRNA levels of the phase I enzymes CYP1A1, CYP1A2 and, to a lesser extent, CYP1B1, in the liver. The Aryl hydrocarbon receptor (AhR) seemed to be involved in this upregulated CYP1 expression. However, a slight trend toward an increase in the mRNA levels of the phase II enzymes GSTP1 and NQO1 was observed with the HOO diet. At least in the case of GSTP1, this effect was linked to an increased Nrf2 transactivation activity. This different regulation of the XMEs expression led, in the case of the HCO diet, to a balance between the production of active carcinogenic compounds and their inactivation tilted toward phase I, which would stimulate DMBA-induced cancer initiation, whereas the HOO diet was associated with a slower phase I metabolism accompanied by a faster phase II detoxification, thus reducing the output of the active compounds to the target tissues. In the mammary gland, the differential effects of diets may be conditioned by the state of cell differentiation, sexual maturity, and hormone metabolism.

Ontogeny of the major xenobiotic-metabolizing enzymes expression and the dietary lipids modulatory effect in the rat dimethylbenz(a)anthracene-induced breast cancer model.

Breast cancer is the most common malignancy in women worldwide. Environmental factors such as xenobiotic exposure and lifestyle and nutrition play a key role in its etiology. This study was designed to evaluate the age-related changes in the expression of major xenobiotic-metabolizing enzymes (XMEs) in the rat liver and the mammary gland in the dimethylbenz(a)anthracene-induced breast cancer model. The influence of dietary lipids on the ontogeny of XMEs was also evaluated. mRNA and protein levels of phase I (CYP1A1, CYP1A2, and CYP1B1) and phase II (NAD(P)H:quinone acceptor oxidoreductase 1 and GSTP1) enzymes were analyzed, as well as their regulation by AhR and Nrf2, respectively. Results showed differences in the phase I enzymes expression, whereas little changes were obtained in phase II. High corn oil and olive oil diets differentially influenced the expression of age-related changes, suggesting that the different susceptibility to xenobiotic exposure depending upon the age may be modulated by dietary factors.

Olive oil and other dietary lipids in breast cancer.

Breast cancer is the most frequent malignant neoplasia among women worldwide. In addition to genetic and endocrine factors, the environment, and specifically nutritional factors, plays a key role in its aetiology. Epidemiological and in particular experimental studies have shown the link between dietary fat and breast cancer. Abundant data have attributed a potentially chemopreventive effect for extra-virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, which is associated with low incidence and mortality rates from chronic diseases such as breast cancer. We have demonstrated the differential modulatory effect of dietary lipids on mammary carcinogenesis, mainly in studies developed in an experimental model. Thus, diets high in n-6 polyunsaturated fatty acids (PUFA) have a clear stimulating influence, whereas EVOO diets mainly have a negative modulatory effect on breast cancer development. The specific mechanisms involved are not fully understood, but nowadays, it is widely accepted that they are numerous and complex. Our group has contributed to improving the knowledge of these mechanisms by demonstrating the influence of dietary lipids on the structure and function of cell membranes, the modulation of cell-signalling transduction pathways, the regulation of gene expression and growth and sexual maturity.

Olive oil, an essential component of the Mediterranean diet, and breast cancer.

OBJECTIVE: The Mediterranean diet has been related to a lower risk of some chronic diseases, including cancer. We aim to gain insight into the effects of the main source of fat of this diet on breast cancer, the most common type of malignancy in women. DESIGN: Data from sixteen experimental series analysing the effects of dietary lipids on mammary carcinogenesis in an animal model, in the context of the international literature on the Mediterranean diet, olive oil and breast cancer risk. SETTING: Experimental and human data on the effects of olive oil and Mediterranean diet on breast cancer. SUBJECTS: An animal model of induced breast cancer and other human and experimental studies in the literature. RESULTS: Diets rich in extra virgin olive oil (EVOO) exert a negative modulatory effect on experimental breast cancer to a weak promoting effect, much lower than that obtained with a high-corn oil diet. EVOO confers to the mammary adenocarcinomas a clinical behaviour and morphological features compatible with low tumour aggressiveness. This differential effect, in relation to other dietary lipids, may be related to a lower effect on body weight and sexual maturation. In addition, EVOO induced different molecular changes in tumours, such as in the composition of cell membranes, activity of signalling proteins and gene expression. All these modifications could induce lower proliferation, higher apoptosis and lower DNA damage. These results, together with the favourable effect of olive oil reported in the literature when it is consumed in moderate quantities, suggest a beneficial influence of EVOO on breast cancer risk. CONCLUSIONS: Consumption of EVOO in moderate quantities and throughout the lifetime appears to be a healthy choice and may favourably influence breast cancer risk.

Diets high in corn oil or extra-virgin olive oil provided from weaning advance sexual maturation and differentially modify susceptibility to mammary carcinogenesis in female rats.

Based on the importance of early-life events in breast cancer risk, we have investigated the effects of high-fat diets on maturation, mammary gland development, and its susceptibility to transformation. Female Sprague-Dawley rats were fed a lowfat (LF), high corn oil (HCO), or high extra-virgin olive oil (HOO) diet from weaning and gavaged with 7,12-dimethylbenz[a]anthracene. Body weight and mass increased in the HCO group compared to the LF group. The vaginal opening was advanced in both high-fat groups, especially in the HCO group. This HCO group also had increased body weight around puberty, more corpora lutea at post-puberty, and tended to have higher kisspeptin levels in the hypothalamus. Both high-fat diets induced subtle modifications in the morphology of the mammary gland, with no changes on ß-casein or hormone receptors expression in the gland. The HCO diet had a clearly stimulating effect of carcinogenesis, inducing the earliest appearance of tumors and the highest tumor incidence and yield, whereas the HOO diet seemed to have a weak enhancing effect, increasing tumor yield. Our data suggest a strong influence of the HCO diet in sexual maturation and mammary cancer risk, while rats fed the HOO diet were more similar to the controls.