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.

Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin.

The aim of this study was to investigate the effects of two phenolic compounds found in extra virgin olive oil, hydroxytyrosol (HT) and luteolin (LUT), on the metabolism of breast cancer (BC) cells of different molecular subtypes. An untargeted metabolomics approach was used to characterize the metabolic responses of both triple-negative MDA-MB-231 cells and hormone-responsive MCF-7 cells to treatment with these phenols. Notably, while some effects were common across both cell types, others were dependent on the cell type, highlighting the importance of cellular metabolic phenotype. Common effects included stimulation of mitochondrial metabolism, acetate production, and formate overflow. On the other hand, glucose metabolism and lactate production were differentially modulated. HT and LUT appeared to inhibit glycolysis and promote the hexosamine biosynthetic pathway in MDA-MB-231 cells, while MCF-7 cells exhibited higher glycolytic flux when treated with phenolic compounds. Another significant difference was observed in lipid metabolism. Treated MDA-MB-231 cells displayed increased levels of neutral lipids (likely stored in cytosolic droplets), whereas treatment of MCF-7 cells with HT led to a decrease in triacylglycerols. Additionally, glutathione levels increased in MDA-MB-231 cells treated with HT or LUT, as well as in MCF-7 cells treated with LUT. In contrast, in HT-treated MCF-7 cells, glutathione levels decreased, indicating different modulation of cellular redox status. Overall, this work provides new insights into the metabolic impact of HT and LUT on different BC cell subtypes, paving the way for a better understanding of the nutritional relevance of these phenolic compounds in the context of BC prevention and management.

Extra-Virgin Olive Oil and Its Minor Compounds Influence Apoptosis in Experimental Mammary Tumors and Human Breast Cancer Cell Lines.

Breast cancer is the most common malignancy among women worldwide. Modifiable factors such as nutrition have a role in its etiology. In experimental tumors, we have observed the differential influence of high-fat diets in metabolic pathways, suggesting a different balance in proliferation/apoptosis. In this work, we analyzed the effects of a diet high in n-6 polyunsaturated fatty acids (PUFA) and a diet high in extra-virgin olive oil (EVOO) on the histopathological features and different cell death pathways in the dimethylbenz(a)anthracene-induced breast cancer model. The diet high in n-6 PUFA had a stimulating effect on the morphological aggressiveness of tumors and their proliferation, while no significant differences were found in groups fed the EVOO-enriched diet in comparison to a low-fat control group. The high-EVOO diet induced modifications in proteins involved in several cell death pathways. In vitro analysis in different human breast cancer cell lines showed an effect of EVOO minor compounds (especially hydroxytyrosol), but not of fatty acids, decreasing viability while increasing apoptosis. The results suggest an effect of dietary lipids on tumor molecular contexts that result in the modulation of different pathways, highlighting the importance of apoptosis in the interplay of survival processes and how dietary habits may have an impact on breast cancer risk.

Influence of Olive Oil and Its Components on Breast Cancer: Molecular Mechanisms.

Breast cancer is the most frequent malignant neoplasia and a leading cause of mortality in women worldwide. The Mediterranean diet has been proposed as a healthy dietary pattern with protective effects in several chronic diseases, including breast cancer. This diet is characterized by the consumption of abundant plant foods and olive oil as the principal source of fat, which is considered one of the main components with potential antioxidant, anti-inflammatory and anticancer effects. Extra-virgin olive oil (EVOO) has several bioactive compounds, mainly including monounsaturated fatty acids, triterpenes and polyphenols, such as phenolic alcohols (e.g., hydroxytyrosol), secoiridoids (e.g., oleuropein and oleocanthal), lignans (e.g., pinoresinol) or flavonoids (e.g., luteolin). While epidemiological evidence is still limited, experimental in vivo and in vitro data have shown a protective effect of this oil and its compounds on mammary carcinogenesis. Such effects account through complex and multiple mechanisms, including changes in epigenetics, transcriptome and protein expression that modulate several signaling pathways. Molecular targets of EVOO compounds have a role in the acquisition of cancer hallmarks. Although further research is needed to elucidate their beneficial effects on human prevention and progression of the disease, evidence points to EVOO in the context of the Mediterranean diet as a heathy choice, while EVOO components may be promising adjuvants in anticancer strategies.

A high extra-virgin olive oil diet induces changes in metabolic pathways of experimental mammary tumors.

Breast cancer is the most common malignancy in women worldwide, and environmental factors, especially diet, have a role in the etiology of this disease. This work aimed to investigate the influence of high fat diets (rich in corn oil or extra virgin olive oil -EVOO-) and the timing of dietary intervention (from weaning or after induction) on tumor metabolism in a seven,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer model in rat. The effects of lipids (oils and fatty acids) have also been investigated in MCF-7 cells. The results have confirmed different effects on tumor progression depending on the type of lipid. Molecular analysis at mRNA, protein and activity level of enzymes of the main metabolic pathways have also shown differences among groups. Thus, the animals fed with the EVOO-enriched diet developed tumors with less degree of clinical and morphological malignancy and showed modified glucose and mitochondrial metabolism when compared to the animals fed with the corn oil-enriched diet. Paradoxically, no clear influence on lipid metabolism by the high fat diets was observed. Considering previous studies on proliferation and apoptosis in the same samples, the results suggest that metabolic changes have a role in the molecular context that results in the modulation of different signaling pathways. Moreover, metabolic characteristics, without the context of other pathways, may not reflect tumor malignancy. The time of dietary intervention plays also a role, suggesting the importance of metabolic plasticity and the relation with mammary gland status when the tumor is induced.

A high-corn-oil diet strongly stimulates mammary carcinogenesis, while a high-extra-virgin-olive-oil diet has a weak effect, through changes in metabolism, immune system function and proliferation/apoptosis pathways.

Breast cancer is the most common malignancy in women worldwide, and dietary lipids are important environmental factors influencing its etiology. We have investigated the effects, and the mechanisms associated, of high-fat diets on 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. Animals were fed a low-fat, a high-corn-oil (HCO) or a high-extra-virgin-olive-oil (HOO) diet from weaning or after induction. The HCO diet had a clear stimulating effect on mammary carcinogenesis, especially when dietary intervention started after induction, whereas the tumors from HOO diet groups exhibited clinical and morphological characteristics similar to those from low-fat controls. Transcriptomic and further protein and immunohistochemical analyses of tumors also indicated different modulatory effects of high-fat diets affecting relevant biological functions: metabolism, immunosurveillance and proliferation/apoptosis pathways. Thus, the results suggested different metabolic adaptations with increased glycolysis by effect of HOO diet. Moreover, leukocyte tumor infiltration and inflammation mediators showed increased cytotoxic T cells and decreased TGFß1 expression by the HOO diet, while the HCO one increased arginase expression and IL-1α plasma levels. Furthermore, the study of proteins controlling proliferation/apoptosis pathways (Sema3A, Stat5, Smad1, Casp3) suggested an increase in proliferation by the HCO diet and an increase of apoptosis by the diet rich in olive oil. In conclusion, the HCO diet clearly stimulated mammary carcinogenesis, especially in the promotion phase, and induced molecular changes suggesting increased tumor proliferation/apoptosis balance and a proinflammatory microenvironment. The HOO diet, despite being high fat, had a weaker effect on tumorigenesis probably related to metabolic adaptations, enhanced immunosurveillance and increased apoptosis.

Gene ontology analysis of transcriptome data from DMBA-induced mammary tumors of rats fed a high-corn oil and a high-extra virgin olive oil diet.

Breast cancer is the most common malignancy in women worldwide, and dietary lipids are important environmental factors influencing its etiology. In this work we present data in relation to the transcriptional effects of two high-fat diets, one high in corn oil (HCO) and one high in extra-virgin olive oil (HOO), administered from weaning or after induction, on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. Raw data were deposited at ArrayExpress under accession number E-MTAB-3541. We compared the gene expression profiles of the mammary tumors from the high-fat diet groups with those from the control group, finding different effects of diets depending on timing and type of dietary intervention. Lists of differentially expressed genes were analyzed to find overrepresented categories of biological significance. Here we provide information about the cell functions categories overrepresented in significantly modulated genes by effect of the high-fat diets. Further investigations of such functions are described in "A high corn oil diet strongly stimulates mammary carcinogenesis, while a high extra virgin olive oil diet has a weak effect, through changes in metabolism, immune system function, and proliferation/apoptosis pathways" (Escrich et al., in press) [1].

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.

Molecular Profiling and Malignant Behavior Define Two Rat Mammary Tumor Cell Lines as a Relevant Experimental Model.

Cancer cell lines have become a reliable tool in genetic and biochemical studies of breast cancer. Here, we described the behavior and novel molecular characterization of two cell lines derived from DMBA-induced rat mammary tumor, LA7 and RBA. LA7 cells have been identified as myoepithelial cells with stem cell properties, whereas the RBA cell line are epithelial cells that present mutational activated H-Ras, but are much less known. We evaluated the proliferation rate and molecular markers, several signaling pathways status related to proliferation, survival, inflammation, and apoptosis, as well as migration capacity, global DNA methylation levels, and stem cells populations. In fact, we found the A/T transversion in the c-Ha-Ras codon 61 as the activator mutation origin described in RBA cells. LA7 and RBA cells showed a high proliferation rate associated with overexpression of Cyclin D1, and resistance to apoptotic signals due to lack of expression of Bad. Moreover, neither of these two cell lines expressed steroid receptors, but they showed high migration capacity, all in accordance with an aggressive phenotype. We found global DNA methylation levels in LA7 and RBA cells lower than reference tissues analyzed, in addition to the presence of different stem cells populations in RBA cell line that differed in the expression of CD44 and CD24. These results revealed a malignant behavior associated with cancer stem cell phenotype. Since this profile is similar to a human triple-negative basal-like tumor, their extensive characterization presented herein increases their value as a good in vitro model. J. Cell. Biochem. 117: 2825-2834, 2016. © 2016 Wiley Periodicals, Inc.

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.

Modulatory effects and molecular mechanisms of olive oil and other dietary lipids in breast cancer.

Breast cancer is the most common cancer among women worldwide. In addition to genetic and endocrine factors, the environment, and specifically dietary habits, plays a key role in the aetiology of this malignancy. Epidemiological and, especially, experimental studies have shown a relationship between dietary lipids and breast cancer although there are conflicting results concerning their potential to modify cancer risk in humans. Abundant data have attributed a potential chemopreventive effect to extra-virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, which is associated with low incidence and mortality rates from cardiovascular disease and some cancers, including that of the breast. It is well-established that the healthy effects of EVOO can be attributed both to its particular fatty acid composition (a high content in oleic acid (OA), a suitable quantity of essential polyunsaturated fatty acids (PUFA) and a relatively low n-6 PUFA/n-3 PUFA ratio) and its richness in minor bioactive compounds such as squalene and phenolic antioxidants. The specific mechanisms by which EVOO and other dietary lipids may exert their modulatory effects on cancer are not fully understood although abundant research has proposed the following: They influence in the stages of the carcinogenesis process, oxidative stress, alteration of the hormonal status, modification of the structure and function of cell membranes, modulation of cell signalling transduction pathways, regulation of gene expression and influence in the immune system. This article will explore the current knowledge of these mechanisms, including our own results in the context of the international literature.