Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Effects on Fetal Metabolic Programming and Endocannabinoid System of a Normocaloric Diet during Pregnancy and Lactation of Female Mice with Pregestational Obesity.

Fetal programming provides explanatory mechanisms for the currently high prevalence of gestational obesity. The endocannabinoid system (ECS) participates in the regulation of energy balance, and with a high-fat diet (HFD), it is overactivated. The aim of this study was to determine the effects of a nutritional intervention during pregnancy and lactation on obese female progenitors, on metabolic alterations of the offspring and on the involvement of ECS. Female mice (C57/BL/6-F0), 45 days old, and their offspring (males) were separated according to type of diet before and during gestation and lactation: CON-F1: control diet; HFD-F1 group: HFD (fat: 60% Kcal); INT-F1 group: HFD until mating and control diet (fat: 10% Kcal) afterward. Glucose tolerance and insulin sensitivity (IS) were tested at 2 and 4 months. At 120 days, mice were sacrificed, plasma was extracted for the determination of hormones, and livers for gene expression and the protein level determination of ECS components. INT-F1 group presented a lower IS compared to CON-F1, and normal levels of adiponectin and corticosterone in relation to the HFD-F1 group. The intervention increased hepatic gene expression for fatty-acid amide hydrolase and monoacylglycerol lipase enzymes; however, these differences were not observed at the protein expression level. Our results suggest that this intervention model normalized some hormonal parameters and hepatic mRNA levels of ECS components that were altered in the offspring of progenitors with pre-pregnancy obesity.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Brain structural parameters correlate with University Selection Test outcomes in Chilean high school graduates.

How well students learn and perform in academic contexts is a focus of interest for the students, their families, and the entire educational system. Although evidence has shown that several neurobiological factors are involved in scholastic achievement (SA), specific brain measures associated with academic outcomes and whether such associations are independent of other factors remain unclear. This study attempts to identify the relationship between brain structural parameters, and the Chilean national University Selection Test (PSU) results in high school graduates within a multidimensional approach that considers socio-economic, intellectual, nutritional, and demographic variables. To this end, the brain morphology of a sample of 102 students who took the PSU test was estimated using Magnetic Resonance Imaging. Anthropometric parameters, intellectual ability (IA), and socioeconomic status (SES) were also measured. The results revealed that, independently of sex, IA, gray matter volume, right inferior frontal gyrus thickness, and SES were significantly associated with SA. These findings highlight the role of nutrition, health, and socioeconomic variables in academic success.

Reduced n-3 and n-6 PUFA (DHA and AA) Concentrations in Breast Milk and Erythrocytes Phospholipids during Pregnancy and Lactation in Women with Obesity.

Obesity during pregnancy is a worrying public health problem worldwide. Maternal diet is critical for fatty acid (FA) placental transport and FA content in breast milk (BM). We evaluated FA composition in erythrocytes phospholipids (EP) and BM in pregnant women with (OBE, n = 30) and without (non-OBE, n = 31) obesity. Sixty-one healthy women were evaluated at their 20-24th gestational week and followed until 6th month of lactation. Diet was evaluated through a food frequency questionnaire. FA composition of EP and BM was assessed by gas-liquid chromatography. The OBE group showed lower diet quality, but total n-6 and n-3 polyunsaturated FA (PUFA), ALA, EPA, and DHA dietary intake was similar between groups. N-3 PUFA, ALA, DHA, and the n-6/n-3 PUFA ratio in EP were lower at the 6th lactation month in the OBE group. In BM, the arachidonic acid (AA) concentration was lower at the end of the lactation, and DHA content showed an earlier and constant decline in the OBE group compared to the non-OBE group. In conclusion, n-3 PUFA and AA and DHA levels were reduced in EP and BM in pregnant women with obesity. Strategies to increase n-3 PUFA are urgently needed during pregnancy and lactation, particularly in women with obesity.

Variabilidad en el diagnóstico nutricional de infantes menores de 12 meses realizados por profesionales nutricionistas

RESUMEN Antecedentes: La malnutrición por exceso (sobrepeso y obesidad) es una condición de alta prevalencia en Chile, para el diagnóstico de esta condición se deben utilizar diversas normativas nacionales, que en su aplicación son afectas a interpretaciones. Objetivo: Evaluar la concordancia en los diagnósticos nutricionales en niños menores de 12 meses entre profesionales nutricionistas. Métodos: Estudio observacional descriptivo de corte transversal con un muestreo no probabilístico por conveniencia. Se masificó un instrumento on-line con 5 casos para realizar el Diagnóstico del Estado Nutricional en grupos de profesionales nutricionistas en redes sociales. Se estableció el grado de concordancia en porcentaje y coeficientes Kappa de Fleiss. Resultados: 104 profesionales completaron el instrumento (3 hombres), la experiencia laboral promedio fue de 4,8 ± 4,7 años, el porcentaje de concordancia varió desde 8% a 81% con valores de Kappa de Fleiss de κ= 0,468 a κ= 0,847. Conclusión: A pesar de existir diversas normativas que regulan la determinación del Diagnóstico Nutricional existe alta variabilidad lo que demuestra la necesidad de crear consensos profesionales.

ABSTRACT Background: Overweight is a highly prevalent condition in Chile. For diagnosis of this condition, various national regulations must be used, but, their application are subject to interpretations, particularly in infants. Aim: To assess the agreement in infant nutritional diagnoses made by nutritionist. Methods: Observational descriptive cross-sectional study with non-probability sampling for convenience. An online instrument with 5 cases was used to carry out Nutritional Status Diagnosis among groups of nutritionists contacted via social networks. Degree of concordance was determined by percentage and Fleiss Kappa coefficients. Results: 104 professionals completed the instrument (3 men), average work experience was 4.8 ± 4.7 years, the percentage of agreement ranged from 8% to 81% with Fleiss Kappa values of κ= 0.468 to κ= 0.847. Conclusion: Although various national guidelines exist on nutritional diagnosis, there is high variability, which demonstrates the need to create professional consensus.

Diet, Plasma, Erythrocytes, and Spermatozoa Fatty Acid Composition Changes in Young Vegan Men.

There has been increasing interest in vegan diets, but how this dietary pattern regulates tissue fatty acids (FA), especially in men, is unclear. Our aim was to evaluate the effect of a vegan diet on plasma, erythrocyte, and spermatozoa FA composition in young men. Two groups consisting of 67 young (18-25 years old) men were studied. One group following an omnivore diet but did not consume fish, shellfish or other marine foods (control, n = 33), and another group following a vegan diet (vegan, n = 34) for at least 12 months were compared. Dietary intake was assessed via a food frequency questionnaire and a 24-h recall. FA composition was measured in plasma, erythrocyte phospholipids, and spermatozoa by gas-liquid chromatography. Compared to controls, the vegan group had higher reported intakes of carbohydrate, dietary fiber, vitamins (C, E, K, and folate), and minerals (copper, potassium) but lower intakes of cholesterol, trans FA, vitamins B6 , D, and B12 , and minerals (calcium, iron, and zinc). Vegan's reported a lower saturated FA and not arachidonic acid intake, both groups did not intake eicosapentaenoic acid and docosahexaenoic acid (DHA), but vegan's showed a higher alpha linolenic acid ALA intake. Vegans had higher plasma, erythrocyte phospholipid, and spermatozoa ALA, but lower levels of other n-3 polyunsaturated fatty acid (PUFA), especially DHA. Vegans were characterized by higher ALA, but lower levels of other n-3 PUFA, especially DHA in plasma, erythrocytes, and spermatozoids. The biological significance of these findings requires further study.

Iron-induced derangement in hepatic Δ-5 and Δ-6 desaturation capacity and fatty acid profile leading to steatosis: Impact on extrahepatic tissues and prevention by antioxidant-rich extra virgin olive oil.

The administration of iron induces liver oxidative stress and depletion of long-chain polyunsaturated fatty acids (LCPUFAs), n-6/n-3 LCPUFA ratio enhancement and fat accumulation, which may be prevented by antioxidant-rich extra virgin olive oil (AR-EVOO) supplementation. Male Wistar rats were subjected to a control diet (50 mg iron/kg diet) or iron-rich diet (IRD; 200 mg/kg diet) with alternate AR-EVOO for 21 days. Liver fatty acid (FA) analysis was performed by gas-liquid chromatography (GLC) after lipid extraction and fractionation, besides Δ-5 desaturase (Δ-5 D) and Δ6-D mRNA expression (qPCR) and activity (GLC) measurements. The IRD significantly (p < 0.05) increased hepatic total fat, triacylglycerols, free FA contents and serum transaminases levels, with diminution in those of n-6 and n-3 LCPUFAs, higher n-6/n-3 ratios, lower unsaturation index and Δ5-D and Δ6-D activities, whereas the mRNA expression of both desaturases was enhanced over control values, changes that were prevented by concomitant AR-EVOO supplementation. N-6 and n-3 LCPUFAs were also decreased by IRD in extrahepatic tissues and normalized by AR-EVOO. In conclusion, AR-EVOO supplementation prevents IRD-induced changes in parameters related to liver FA metabolism and steatosis, an effect that may have a significant impact in the treatment of iron-related pathologies or metabolic disorders such as non-alcoholic fatty liver disease.

A multifactorial approach of nutritional, intellectual, brain development, cardiovascular risk, socio-economic, demographic and educational variables affecting the scholastic achievement in Chilean students: An eight- year follow-up study.

The aim of this study was to quantitate the relative impact of nutritional, intellectual, brain development, cardiovascular risk, socio-economic, demographic and educational variables on the results of the 2009 Quality Education Measurement System (SIMCE) tests of language and mathematics for scholastic achievement (SA) applying a multifactorial approach, in school-age children of the 2010 5th elementary school grade (5ESG) and of the 1st grade of high school (1HSG). The purposes were: i) to test the hypothesis that intellectual ability, the level of SA of the educational establishments in the 2009 SIMCE tests, sex, parental schooling levels, and head circumference-for-age Z-score are the most relevant parameters associated with 2009 SIMCE outcomes; ii) to determine the predictive ability of the 2009 SIMCE results in determining the 2013 SIMCE outcomes for the 2010 5ESG cohort (when they graduated from elementary school, 8th grade) and for determining the 2013 University Selection Test (PSU) outcomes for the 2010 1HSG group (for university admission, when they graduated from high school, 4th grade); iii) to determine the association between the 2009 SIMCE results with the 2017 PSU outcomes for the 2010 5ESG group (for university admission, when they graduated from high school, 4th grade). A representative, proportional and stratified sample of 33 schools of the Metropolitan Region of Chile was randomly chosen. In these schools, 1,353 school-age children of both sexes, of the 2010 5ESG (n = 682; mean age = 10.8 years, SD = 0.6) and of the 2010 1HSG (n = 671; mean age = 14.8 years, SD = 0.6) participated. In both grades and tests, the findings confirm the hypotheses formulated. 2009 SIMCE outcomes were positively and significantly associated with 2013 SIMCE and with 2017 PSU and, with 2013 PSU outcomes in school-age children from 2010 5ESG and 1HSG, respectively. These findings may be useful for educational and health planning in Chile and countries in a comparable stage of development.

Impact of anthropometric nutritional parameters on the university selection test in Chile: A multifactorial approach.

OBJECTIVES: Scholastic achievement (SA) is a multifactorial problem that depends on factors related to the child, the child's family, and the educational system. The aim of this study was to quantify the relative impact of significant variables at the beginning of high school during 2010 (first grade of high school [1 HSG]) on 2013 university selection test (Prueba de Seleccion Universitaria [PSU]) outcomes, both in language scholastic achievement (LSA) and mathematics scholastic achievement (MSA), when students graduated from high school (4 HSG). This was done at the time of university admission with a multicausal approach. The purpose was to confirm the hypothesis that the level of educational establishment SA, intellectual ability, sex, parental schooling levels, and head circumference for age Z-score at the onset of high school are the most relevant parameters associated with 2013 PSU outcomes, both in LSA and MSA. METHODS: A representative, proportional, and stratified sample of 671 children of both sexes who enrolled in 1 HSG in 2010 (mean age: 14.8 ± 0.6 y) participated in the study. Nutritional, intellectual, brain developmental, cardiovascular risk, socio-to-economic, demographic, and educational variables were quantitated. SA was assessed at 4 HSG with the 2013 PSU tests. Data were analyzed with SAS software. RESULTS: Educational establishment SA, intellectual ability, maternal schooling, and age Z-score were the most relevant parameters to explain LSA (R2 = 0.493; P < 0.0001) and MSA variance in addition to sex (male), but only in MSA (R2 = 0.600; P < 0.0001). CONCLUSIONS: These findings confirm the hypothesis and can be useful to support nutritional, health, and educational planning.

Docosahexaenoic acid levels in erythrocytes and their association with the University Selection Test Outcomes in Chile.

The aim of this study was to quantitate the relative impact of DHA and AA levels in erythrocytes, anthropometric parameters and socio-economic status of school-age children, of both genders, graduated from high school in Chile, on the scholastic achievement in the University Selection Test (Prueba de Selección Universitaria, PSU) both language scholastic achievement (LSA) and mathematics scholastic achievement (MSA). A representative sample of 671 school-age young graduated from high school in 2013, 550 and 548 of them took the PSU for LSA and MSA, respectively. Only school-age young with high (n = 91) and low (n = 69) SA in both tests were considered. A total of 122 school-age children agreed to participate in the study and were divided as follows: Group 1: high PSU outcome (n = 70; males n = 48) and Group 2: low PSU outcome (n = 52; males n = 23). Data were analyzed by means of SAS software. Independently of gender, DHA, socio-economic status and head circumference-for-age Z-score were the most relevant parameters explaining both LSA (R2 = 0.650; p < 0.0001) and MSA outcomes (R2 = 0.700; p < 0.0001). These results can be useful for nutrition, health and education planning, in order to protect children starting from an early age and thus increase their school outcomes.

Overnutrition and Scholastic Achievement: Is There a Relationship? An 8-Year Follow-Up Study.

OBJECTIVE: The aim of this study was to assess the association between overnutrition and scholastic achievement (SA). METHODS: A representative and proportional sample of 477 children of the 5th elementary school grade of both genders was randomly chosen during 2010, in the Metropolitan Region of Chile. SA was measured through the 2009 Education Quality Measurement System (SIMCE) tests of language (LSA), mathematics (MSA) and understanding of the natural environment (UNESA). Current nutritional status was assessed through the body mass index Z-score (Z-BMI). Nutritional quality of diet, schedule exercise, socioeconomic status, family, and educational variables were also recorded. Four and 8 years later, SA was assessed through the 2013 SIMCE and the University Selection Test (2017 PSU), respectively. RESULTS: Socioeconomic status, the number of repeated school years, and maternal schooling were strong predictors of 2009 SIMCE and the independent variables with the greatest explanatory power for LSA (Model R2 = 0.178; p < 0.00001) variances, besides of gender for MSA (Model R2 = 0.205; p< 0.00001) and UNESA (Model R2 = 0.272; p < 0.00001). Overnourished children did not have significantly lower 2009 and 2013 SIMCE and 2017 PSU outcomes. CONCLUSIONS: These results confirm that overnourished children did not achieve significantly lower SA.

Molecular mechanisms related to the hepatoprotective effects of antioxidant-rich extra virgin olive oil supplementation in rats subjected to short-term iron administration.

Enhanced iron levels in liver are associated with oxidative stress development and damage with increased fat accumulation. The aim of this work was to assess the hypothesis that antioxidant-rich extra virgin olive oil (AR-EVOO) counteracts iron-rich diet (IRD)-induced oxidative stress hindering hepatic steatosis. Male Wistar rats were fed and IRD (200 mg iron/kg diet) versus a control diet (CD; 50 mg iron/kg diet) with alternate AR-EVOO supplementation (100 mg/day) for 21 days. IRD induced liver steatosis and oxidative stress (higher levels of protein oxidation and lipid peroxidation with glutathione depletion), mitochondrial dysfunction (decreased citrate synthase and complex I and II activities) and loss of polyunsaturated fatty acids (PUFAs), with a drastic enhancement in the sterol regulatory element-binding protein-1c (SREBP-1c)/peroxisome proliferator-activated receptor-α (PPAR-α) ratio upregulating the expression of lipogenic enzymes (acetyl-CoA carboxylase, fatty acid (FA) synthase and stearoyl desaturase 2) and downregulating those involved in FA oxidation (carnitine palmitoyl transferase and acyl-CoA oxidase) over values in the CD group. IRD also upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and its target genes. AR-EVOO supplementation alone did not modify the studied parameters, however, IRD combined with AR-EVOO administration returned IRD-induced changes to baseline levels of the CD group. It is concluded that IRD-induced non-alcoholic fatty liver disease (NAFLD) is prevented by AR-EVOO supplementation, which might be related to the protective effects of its components such as hydroxytyrosol, oleic acid, tocopherols and/or PUFAs, thus representing a suitable anti-steatotic strategy to avoid progression into more severe stages of the disease, underlying NAFLD associated with iron overloading pathologies or obesity.

The Impact of Maternal Diet during Pregnancy and Lactation on the Fatty Acid Composition of Erythrocytes and Breast Milk of Chilean Women.

Maternal diet during pregnancy is relevant for fatty acid supply during fetal life and lactation. Arachidonic (AA) and docosahexaenoic (DHA) acids are also relevant for the normal growth and development of brain and visual system. AA and DHA provided by the mother to the fetus and infant are directly associated with maternal dietary intake and body stores. Our aim was to evaluate the impact of maternal diet, specially referring to the quality of fatty acid intake, in a sample of Chilean women during last stage of pregnancy and across the lactation period. Fifty healthy pregnant women (age range 20⁻33 years) were studied from the 6th month of pregnancy and followed until 6th month of lactation period. Diet characteristics were evaluated through food frequency questionnaires. Fatty acids composition of erythrocyte phospholipids and breast milk samples was assessed by gas-liquid chromatography. Overall, women had high saturated fatty acids intake with sufficient intake of mono- and polyunsaturated fatty acids (PUFA). Diet was high in n-6 PUFA and low in n-3 PUFA (mainly DHA), with imbalanced n-6/n-3 PUFA ratio. Erythrocytes and breast milk DHA concentration was significantly reduced during lactation compared to pregnancy, a pattern not observed for AA. We concluded that is necessary to increase the intake of n-3 PUFA during pregnancy and lactation by improving the quality of consumed foods with particular emphasis on its DHA content.

Iron-induced pro-oxidant and pro-lipogenic responses in relation to impaired synthesis and accretion of long-chain polyunsaturated fatty acids in rat hepatic and extrahepatic tissues.

OBJECTIVES: Iron is involved in processes involving oxygen transfer and utilization. Excess iron is linked to cardiovascular diseases and some types of cancer. Iron overload is associated with oxidative stress development, and may have important interactions with lipid metabolism in the liver favoring the development and progression of non-alcoholic fatty liver disease. The aim of the study described here was to assess the effect of high intake of iron on oxidative stress-related parameters, lipid metabolism, and levels of long-chain polyunsaturated fatty acids (LCPUFAs) in liver and other tissues of the rat. METHODS: Male Wistar rats (21 d old) were fed an iron-rich diet (200 mg iron/kg diet, IRD) versus a control diet (50 mg iron/kg diet; CD) for 21 d. Samples of erythrocytes, liver, adipose tissue, brain, heart, and testicles were evaluated for fatty acid composition and hepatic biochemical and oxidative stress parameters, Δ-6 and Δ-5 desaturase activities, SREBP-1c and PPAR-α mRNA expression and DNA-binding capacity, and lipolytic, lipogenic, and antioxidant enzymatic activities. RESULTS: The IRD caused liver steatosis and increased activity of plasma transaminases, with higher oxidative stress status in plasma and liver. Liver Δ-6 and Δ-5 desaturase exhibited decreased activity, but enhanced expression in response to the IRD compared with the CD, with lower levels of ω-3 and ω-6 LCPUFAs and higher expression and DNA binding of SREBP-1c, whereas expression and DNA-binding activity of PPAR-α were diminished. CONCLUSIONS: IRD induced oxidative stress and a reduction in the desaturation capacity of the liver, with LCPUFA depletion in the different tissues studied, thus promoting a pro-steatotic condition in the liver.

Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats.

Alpha-linolenic acid (C18:3 n-3, ALA) is an essential fatty acid and the metabolic precursor of long-chain polyunsaturated fatty acids (LCPUFA) from the n-3 family with relevant physiological and metabolic roles: eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA). Western diet lacks of suitable intake of n-3 LCPUFA and there are recommendations to increase the dietary supply of such nutrients. Seed oils rich in ALA such as those from rosa mosqueta (Rosa rubiginosa), sacha inchi (Plukenetia volubis) and chia (Salvia hispanica) may constitute an alternative that merits research. This study evaluated hepatic and epididymal accretion and biosynthesis of n-3 LCPUFA, the activity and expression of Δ-5 and Δ-6 desaturase enzymes, the expression and DNA-binding activity of PPAR-α and SREBP-1c, oxidative stress parameters and the activity of antioxidative enzymes in rats fed sunflower oil (SFO, 1% ALA) as control group, canola oil (CO, 10% ALA), rosa mosqueta oil (RMO, 33% ALA), sacha inchi oil (SIO, 49% ALA) and chia oil (ChO, 64% ALA) as single lipid source. A larger supply of ALA increased the accretion of n-3 LCPUFA, the activity and expression of desaturases, the antioxidative status, the expression and DNA-binding of PPAR-α, the oxidation of fatty acids and the activity of antioxidant enzymes, whereas the expression and DNA-binding activity of SREBP-1c transcription factor and the biosynthetic activity of fatty acids declined. Results showed that oils rich in ALA such as SIO and ChO may trigger metabolic responses in rats such as those produced by n-3 PUFA.

Anti-steatotic effects of an n-3 LCPUFA and extra virgin olive oil mixture in the liver of mice subjected to high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is characterized by liver steatosis, oxidative stress, and drastic depletion of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), namely, eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA), which trigger lipolysis stimulation and lipogenesis inhibition. Extra virgin olive oil (EVOO) has important antioxidant effects. This study evaluated the anti-steatotic effects of n-3 LCPUFA plus EVOO in the liver of male C57BL/6J mice subjected to a control diet (CD) (10% fat, 20% protein, 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, 20% carbohydrate), without and with supplementation with n-3 LCPUFA (100 mg per kg per day) plus EVOO (100 mg per kg per day) for 12 weeks. HFD induced (i) liver steatosis (increased total fat, triacylglycerols, and free fatty acid total contents), (ii) higher fasting serum glucose and insulin levels and HOMA index, total cholesterol, triacylglycerols and TNF-α and IL-6, (iii) liver and plasma oxidative stress enhancement, (iv) depletion of the n-3 LCPUFA hepatic content, and (v) increment in lipogenic enzyme activity and reduction in lipolytic enzyme activity. These changes were either reduced (p < 0.05) or normalized to control the values in animals subjected to HFD supplemented with n-3 LCPUFA plus EVOO. In conclusion, n-3 LCPUFA plus EVOO intervention exerts anti-steatotic effects underlying antioxidant and anti-inflammatory responses, improved insulin sensitivity, and recovery of the lipolytic/lipogenic status of the liver altered by HFD, and supports the potential therapeutic use of n-3 LCPUFA plus EVOO supplementation in the treatment of human liver steatosis induced by nutritional factors or other etiologies.

Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing.

α-Linolenic acid (ALA) is the precursor of docosahexaenoic acid (DHA) in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L.), a plant native to some Latin American countries, is high in ALA (up to 60%) and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22-35 years old) tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21) and a chia group (n = 19), which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i) a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA) ingestion, no showing modification of arachidonic acid (AA), eicosapentaenoic acid (EPA) and DHA; (ii) a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii) a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA.

Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: Relation to LCPUFA depletion in liver and extrahepatic tissues.

α-Linolenic (ALA) and linoleic (LA) acids are precursors of long chain polyunsaturated fatty acids (LCPUFAs), FAs with important biochemical and physiological functions. In this process, desaturation reactions catalyzed by Δ5- and Δ6-desaturase play a major role, enzymes that are subjected to hormonal and dietary regulation. The aim of this study was to assess the influence of a high fat diet (HFD) on activity of liver Δ5 and Δ6 desaturases, in relation to LCPUFA composition in liver and extrahepatic tissues. Male C57BL/6J mice received control diet (CD) (10% fat, 20% protein and 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, and 20% carbohydrate) for 12 weeks. After this time, blood and liver samples were taken for metabolic, morphologic, inflammatory, oxidative stress and desaturase activity assessment, besides FA phospholipid analysis in erythrocytes, heart, adipose tissue and brain. HFD significantly increased hepatic total fat, triacylglycerides and free FA content with macrovesicular steatosis and oxidative stress enhancement, concomitantly with higher fasting serum glucose and insulin levels, HOMA, and serum cholesterol, triacylglycerols, TNF-α, and IL-6. Diminution in liver Δ5- and Δ6-desaturase activities and LCPUFA depletion were induced by HFD, the later finding being also observed in extrahepatic tissues. In conclusion, HFD-induced reduction in the bioavailability of liver LCPUFA is associated with defective desaturation of ALA and LA, with Δ5- and Δ6-desaturase activities being correlated with insulin resistance development. Data analyzed point to the liver as a major organ responsible for extrahepatic LCPUFA homeostasis, which is markedly deranged by HFD.

Polyunsaturated fatty acid composition of maternal diet and erythrocyte phospholipid status in Chilean pregnant women.

Chilean diets are characterized by a low supply of n-3 polyunsaturated fatty acids (n-3 PUFA), which are critical nutrients during pregnancy and lactation, because of their role in brain and visual development. DHA is the most relevant n-3 PUFA in this period. We evaluated the dietary n-3 PUFA intake and erythrocyte phospholipids n-3 PUFA in Chilean pregnant women. Eighty healthy pregnant women (20-36 years old) in the 3rd-6th month of pregnancy were included in the study. Dietary assessment was done applying a food frequency questionnaire, and data were analyzed through the Food Processor SQL® software. Fatty acids of erythrocyte phospholipids were assessed by gas-liquid chromatography. Diet composition was high in saturated fat, low in mono- and PUFA, high in n-6 PUFA (linoleic acid) and low in n-3 PUFA (alpha-linolenic acid and DHA), with imbalance in the n-6/n-3 PUFA ratio. Similar results were observed for fatty acids from erythrocyte phospholipids. The sample of Chilean pregnant women showed high consumption of saturated fat and low consumption of n-3 PUFA, which is reflected in the low DHA content of erythrocyte phospholipids. Imbalance between n-6/n-3 PUFA could negatively affect fetal development. New strategies are necessary to improve n-3 PUFA intake throughout pregnancy and breast feeding periods. Furthermore, it is necessary to develop dietary interventions to improve the quality of consumed foods with particular emphasis on n-3 PUFA.