Olive Oil, Palm Oil, and Hybrid Palm Oil Distinctly Modulate Liver Transcriptome and Induce NAFLD in Mice Fed a High-Fat Diet.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. The most severe form is nonalcoholic steatohepatitis (NASH). Among risk factors for the development of NAFLD is excessive lipid intake. Since palm (P) oil is the most consumed oil in the world, we aimed to investigate the effects of high-fat diets made with P oil, hybrid palm (HP) oil, or olive (O) oil in liver. Twenty-four male mice (C57Bl/6J) were fed a high-fat diet (41% fat) containing P, HP, or O oils for 8 weeks and compared to a control (C) group fed a chow diet. Adiposity was measured with computed tomography. Body, adipose tissue, and liver weights, as well as liver fat (Bligh⁻Dyer), blood lipid profile, glucose, and liver enzymes were measured. Liver histology (hematoxylin⁻eosin) and transcriptome (microarray-based) were performed. ANOVA tests with Newman⁻Keuls were used. Body weight was increased in the P group (p < 0.001) and body fat in the O group (C vs. O p ≤ 0.01, P vs. O p ≤ 0.05, HP vs. O p ≤ 0.05). All high-fat diets disturbed the blood lipid profile and glucose, with marked effects of HP on very low-density lipoprotein cholesterol (VLDL), triglycerides, and alkaline phosphatase (p ≤ 0.001). HP had the highest liver fat (42.76 ± 1.58), followed by P (33.94 ± 1.13). O had a fat amount comparable to C (16.46 ± 0.34, 14.71 ± 0.70, respectively). P and HP oils induced hepatocyte ballooning. Transcriptome alterations of the O group were related to amino acid metabolism and fatty acid (FA) metabolism, the P group to calcium ion homeostasis, and HP oil to protein localization. Both P and HP oils induced NASH in mice via disturbed hepatocyte transcription. This raises concerns about the content of these oils in several industrialized foods.

Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR.

Consumption of distinct dietary lipids during early pregnancy differentially modulates the expression of microRNAs in mothers and offspring.

Diet during pregnancy and lactation influences the offspring's health in the long-term. Indeed, human epidemiological studies and animal experiments suggest that different type of fatty acids consumption during pregnancy affect offspring development and susceptibility to metabolic disorders. Epigenetic changes are thought to be elicited by dietary factors during critical timing of development. microRNAs (miRNAs) are versatile regulators of gene expression. Thus, we aimed to determine the influence of different fatty acids on miRNA expression in offspring when given during early pregnancy. We fed pregnant either soybean (SO), olive (OO), fish (FO), linseed (LO), or palm-oil (PO) diets from conception to day 12 of gestation; and standard diet thereafter. miRNA expression was assessed in liver an adipose tissue of pregnant rats and their virgin counterparts. While liver concentrations of fatty acids in pregnant or virgin rats replicated those of the diets consumed during early pregnancy, their pups' liver tissue marginally reflected those of the respective experimental feeds. By contrast, the liver fatty acid profile of adult offsprings was similar, regardless of the diet fed during gestation. Different parental miRNAs were modulated by the different type of fatty acid: in adult offspring, miR-215, miR-10b, miR-26, miR-377-3p, miR-21, and miR-192 among others, were differentially modulated by the different fatty acids fed during early pregnancy. Overall, our results show that maternal consumption of different types of fatty acids during early pregnancy influences miRNA expression in both maternal and offspring tissues, which may epigenetically explain the long-term phenotypic changes of the offspring.

Sex-dependent nutritional programming: fish oil intake during early pregnancy in rats reduces age-dependent insulin resistance in male, but not female, offspring.

Prenatal and early postnatal nutritional status may predispose offspring to impaired glucose tolerance and changes in insulin sensitivity in adult life. The long-term consequences of changes in maternal dietary fatty acid composition were determined in rats. From day 1 until day 12 of pregnancy, rats were given isocaloric diets containing 9% nonvitamin fat based on soybean, olive, fish (FO), linseed, or palm oil. Thereafter, they were maintained on the standard diet; offspring were studied at different ages. Body weight at 4, 8, and 12 mo and lumbar adipose tissue and liver weights at 12 mo did not differ between females on the different diets, whereas in males the corresponding values were all lower in the offspring from the FO group compared with the other dietary groups. Plasma glucose concentrations (both basal and after an oral glucose load) did not change with sex or dietary group, but plasma insulin concentrations were lower in females than in males and, in males, were lowest in the FO group. Similar relations were found with both the homeostasis model assessment of insulin resistance and insulin sensitivity index. In conclusion, the intake of more n-3 fatty acids (FO diet) during early pregnancy reduced both fat accretion and age-related decline in insulin sensitivity in male offspring but not in females. It is proposed that the lower adiposity caused by the increased n-3 fatty acids during the intrauterine life was responsible of the lower insulin resistance in male offspring.

Composition of fatty acids in the maternal and umbilical cord plasma of adolescent and adult mothers: relationship with anthropometric parameters of newborn.

BACKGROUND: Considering the importance of long chain polyunsaturated fatty acids to fetal development and the lack of studies that have compared the status of fatty acids between adolescents and adults mothers, the purpose of this study was to evaluate the composition of fatty acids in maternal and umbilical cord plasma from adolescent and adults mothers. METHODS: Forty pregnant adolescents and forty pregnant adults were selected to assess the distribution profile of fatty acids in the maternal and umbilical cord plasma. Quantification of fatty acids in the total lipids of the sample groups was performed through the use of gas-liquid chromatography. RESULTS: The maternal and umbilical cord plasma of the adolescents showed a greater concentration of AA than did that of the adults (P < 0.05). However, a greater percentage of EPA was found in the umbilical cord plasma of the adults (P < 0.05). DHA in the plasma of the adolescent mothers correlated positively to birth weight and head circumference. CONCLUSIONS: This suggests that in situations of greater nutritional risk, as in adolescent pregnancy, n-3PUFA concentrations have a greater influence on the proper development of newborns. Moreover, variations in fatty acid concentrations in the maternal and cord plasma of adolescents and adults may indicate that pregnancy affects the LC-PUFA status of adults and adolescents in distinct ways.

Dietary lipids during early pregnancy differently influence adipose tissue metabolism and fatty acid composition in pregnant rats with repercussions on pup's development.

Pregnant rats received soybean (SO), olive (OO), fish (FO) and linseed (LO) oil diets from conception to d12 of gestation (early diets) and standard diet thereafter. At d12 and d20 the lipoprotein lipase (LPL) activity was evaluated in maternal adipose tissues (ATs). Fatty Acid (FA) profile was determined in maternal lumbar AT (LAT), in milk and in pup's plasma and brain. LPL activity was higher in ATs at d12 than d20, all groups presenting hypertriglyceridemia at d20. At d12, the LO diet resulted higher LPL activity and incorporation of 18:3 n-3 into LAT. FA profile in maternal LAT at d20 and colostrum was similar to early diets, reflected also in FA composition of pup's plasma. In FO, brain phospholipids had higher 22:6 n-3 without affecting arachidonic acid. These results suggest that specifics dietary FA in early pregnancy modulates lipid metabolism and the provision of LC-PUFA in milk and pups brain.

Ethanol Intake during Lactation Alters Milk Nutrient Composition and Growth and Mineral Status of Rat Pups

Lactating Wistar rats were fed a liquid diet containing either ethanol [ethanol-fed group (EFG)] or an isocaloric amount of carbohydrate [pair-fed group (PFG)] from day 1 postpartum up to day 14 of lactation, to investigate micro/macronutrient milk composition and the mineral status of pups. EFG presented a reduction of daily milk production and milk composition was significantly higher in protein and lower in carbohydrate, while the lipid content was similar to that of PFG. When compared to PFG, the milk of EFG had a decreased proportion of C22:6 n-3 fatty acid and an increase in medium-chain fatty acids and of several minerals. Pups of EFG showed reduced growth and a lower concentration of Cu and Sr in plasma and lower concentrations of Ca, P and Cl, and higher concentrations of Cd in the brain. We conclude that maternal EtOH intake greatly impairs lactational performance and modifies the mineral status of pups.

Effects of the fish-oil supplementation on the immune and inflammatory responses in elite swimmers.

The effect of fish-oil supplementation (FO-S) on the immune responses of elite swimmers was investigated. In a randomized placebo-controlled trial, swimmers received either fish-oil capsules (n=10) containing long chain polyunsaturated fatty acids (FA) of n-3 (LCPUFA n-3) or placebo capsules (n=10), both for 6 weeks. Plasma FA, immunological markers, insulin and cortisol were evaluated. The FO-S resulted in an increase in LCPUFA n-3 and a decrease in arachidonic n-6 FA in plasma and a reduction in the production of interferon-gamma by cultured cells. A reduction in the production of tumor necrosis factor-alpha was observed in both groups. An increase in interleukin-2 production and no significant difference in interleukin-4 were also observed. FO-S was able to attenuate the exercise-induced increases in prostaglandin E2. Circulating concentrations of insulin did not change, while cortisol and glucose showed increase after the study period. These results suggest that FO-S influence exercise-associated immune responses in competitive swimmers.

Intake of trans fatty acid-rich hydrogenated fat during pregnancy and lactation inhibits the hypophagic effect of central insulin in the adult offspring.

OBJECTIVE: Using rats we examined whether maternal intake of hydrogenated fat rich in trans fatty acids affects brain fatty acid profile, hypothalamic content of insulin receptor and insulin receptor substrate-1 proteins, and the hypophagic effect of centrally administered insulin in 3-mo-old male progeny. METHODS: Throughout pregnancy and lactation, Wistar rats ate isocaloric/normolipidic diets with soybean oil (control) or soybean oil-derived hydrogenated fat (trans diet) as a fat source. Upon weaning, the trans offspring continued on the trans diet (trans group) or were switched to a control diet (trans-control group). RESULTS: Compared with control rats, trans rats had lower brain levels of eicosapentaenoic acid. Compared with trans rats, trans-control rats had increased levels of total polyunsaturated fatty acids and arachidonic acid and decreased levels of trans fatty acids, saturated fatty acids, and monounsaturated fatty acids. Insulin receptor and insulin receptor substrate-1 levels were significantly lower (44% and 38%, respectively) in trans than in control rats. In trans-control rats, insulin receptor was 26% lower (P < 0.05), whereas insulin receptor substrate-1 was 50% lower, than in control rats. Insulin decreased 24-h feeding in control (27%) and trans (38%) rats but failed to do so in trans-control rats. The latter group had increased serum glucose levels. CONCLUSIONS: The data suggest that the early (intrauterine/perinatal) exposure to hydrogenated fat rich in trans fatty acids programmed the hypothalamic feeding control mechanisms. As young adults, only trans-control animals showed loss of insulin-induced hypophagia, indicating that the mismatch between early and later nutritional environments was relevant. However, the trans group also showed signs of altered appetite signaling mechanisms, suggesting that the early adaptations may have deleterious consequences later in life.