Metabolic and molecular effects of dietary extra virgin olive oil in blood and placenta of women with GDM.

Gestational diabetes mellitus (GDM) increases the risks of maternal, placental, and neonatal complications. Previously, we found that a diet enriched in extra virgin olive oil (EVOO) prevents increased maternal triglyceridemia and placental proinflammatory markers in a cohort of GDM patients. The aim of this work was to evaluate maternal circulating markers of insulin resistance, placental collagen, glycogen and lipid levels, and placental levels of proteins, mRNAs, and a microRNA involved in the endocytic pathway in the same cohort of control women and women with GDM who received or did not receive a diet enriched in EVOO (36 g/day) from weeks 24 to 28 of pregnancy until term. Results: At term, the TG/HDL cholesterol ratio, fatty acid binding protein 4 circulating levels, and maternal BMI were increased in the GDM patients, alterations prevented by the maternal diet enriched in EVOO. Although there were no changes in placental lipid levels and lipid profile, GDM placentas were thicker than controls and showed increased glycogen and collagen content, alterations prevented by the EVOO enriched diet. GDM placentas showed increases in megalin levels, in the expression of several genes involved in the endocytic pathway, and in miR-199, which targets these genes, alterations prevented by the maternal diet enriched in EVOO. Conclusions: We identified novel beneficial effects of an EVOO-enriched diet in GDM women, a diet capable of regulating maternal insulin resistance, the structure and metabolism of the placenta, and the placental endocytic pathway, suggesting effects that may be beneficial for fetal development.

Unsaturated Fatty Acid Intake During Periconception and Incidence of Achieving Pregnancy: A Systematic Review and Meta-Analysis.

Background: Previous studies suggest that maternal diets enriched in unsaturated fatty acids may have a positive effect on pregnancy success. The aim of the present study was to conduct a systematic review and meta-analysis to evaluate whether increased dietary intake of polyunsaturated fatty acids (PUFAs) or monounsaturated fatty acids (MUFAs) during the periconception period has beneficial effects on the achievement of pregnancy in women. Methods: The electronic databases PubMed, Medline and Cochrane Central Register, as well as references in related review articles, were searched to find studies assessing the effects of unsaturated fatty acid dietary intake during the periconception period on the achievement of pregnancy in women. Pregnancy was confirmed by high levels of hCG (biochemical means) and ultrasound confirmation of a gestational sac and heartbeat (clinical means). Results: For the meta-analysis evaluating the effects of periconceptional diets enriched in PUFAs on pregnancy, four articles, providing data on 2,121 patients, were included. Results showed that periconceptional intake of PUFAs has no significant effects on achieving pregnancy compared to controls, according to both the fixed effects and random effects models (RR = 0.99, 95% CI 0.98-1.00). Further secondary analysis considering ω-6 and ω-3 PUFAs separately showed no significant effects on achieving pregnancy compared to controls. On the other hand, for the meta-analysis evaluating the effects of periconceptional diets enriched in MUFAs on achieving pregnancy, five articles, providing data on 2,473 patients, were included. Results showed that periconceptional dietary intake of MUFAs has significant effects on achieving pregnancy compared to controls according to the fixed effects model (RR = 1.03, 95% CI 1.01-1.06, p < 0.02) but not to the random effects model, due to heterogeneity. A secondary meta-analysis excluding one study which led to heterogeneity showed significant effects of MUFAs on achieving pregnancy compared to controls, according to both the fixed effects and random effects models (RR = 1.03, 95% CI 1.01-1.05, p < 0.02). Conclusion: The meta-analysis of published clinical studies suggests that diets enriched in MUFAs, although not those enriched in PUFAs, may have a positive effect on pregnancy success as determined by HCG and ultrasonography. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021239355, identifier: CRD42021239355.

Olive oil supplementation prevents extracellular matrix deposition and reduces prooxidant markers and apoptosis in the offspring´s heart of diabetic rats.

Maternal diabetes induces fetal programming of cardiovascular diseases. Diabetes induced-cardiac fibrosis is a process that may start in utero and may be related to the prooxidant/proinflammatory environment. The aim of this study was to investigate the effect of a maternal diet enriched in olive oil on the levels of components and regulators of the extracellular matrix, on prooxidant markers and on apoptosis rate in the heart of 21-day-old offspring of diabetic rats. Maternal diabetes was induced by neonatal administration of streptozotocin. During pregnancy, diabetic and control rats were fed with diets supplemented or not with 6% olive oil. The heart of the offspring was studied at 21 days of age. We found increased deposition of collagen IV and fibronectin in the offspring´s heart of diabetic rats, which was prevented by the maternal diets enriched in olive oil. Increases in connective tissue growth factor were also prevented by the maternal diets enriched in olive oil. Prooxidant markers as well as apoptosis, which were increased in the heart of the offspring of diabetic rats, were prevented by the maternal olive oil dietary treatment. Our findings identified powerful effects of a maternal diet enriched in olive oil on the prevention of increased extracellular matrix deposition and increased prooxidant markers in the heart of 21-day-old offspring of diabetic rats.

An extra virgin olive oil-enriched diet improves maternal, placental, and cord blood parameters in GDM pregnancies.

AIMS: To address the effect of a diet enriched in extra virgin olive oil (EVOO) on maternal metabolic parameters and placental proinflammatory markers in Gestational diabetes mellitus (GDM) patients. METHODS: Pregnant women at 24-28 weeks of gestation were enrolled: 33 GDM patients which were randomly assigned or not to the EVOO-enriched group and 17 healthy controls. Metabolic parameters were determined. Peroxisome proliferator activated receptor (PPAR) γ and PPARα protein expression, expression of microRNA (miR)-130a and miR-518d (which respectively target these PPAR isoforms) and levels of proinflammatory markers were evaluated in term placentas. Matrix metalloproteinases (MMPs) activity was evaluated in term placentas and umbilical cord blood. RESULTS: GDM patients that received the EVOO-enriched diet showed reduced pregnancy weight gain (GDM-EVOO:10.3 ± 0.9, GDM:14.2 ± 1.4, P = .03) and reduced triglyceridemia (GDM-EVOO:231 ± 14, GDM:292 ± 21, P = .02) compared to the non-EVOO-enriched GDM group. In GDM placentas, the EVOO-enriched diet did not regulate PPARγ protein expression or miR-130a expression, but prevented the reduced PPARα protein expression (P = .02 vs GDM) and the increased miR-518d expression (P = .009 vs GDM). Increased proinflammatory markers (interleukin-1ß, tumour necrosis factor-α and nitric oxide overproduction) in GDM placentas were prevented by the EVOO-enriched diet (respectively P = .001, P = .001 and P = .01 vs GDM). MMPs overactivity was prevented in placenta and umbilical cord blood in the EVOO-enriched GDM group (MMP-9: respectively P = .01 and P = .001 vs GDM). CONCLUSIONS: A diet enriched in EVOO in GDM patients reduced maternal triglyceridemia and weight gain and has antiinflammatory properties in placenta and umbilical cord blood, possibly mediated by the regulation of PPAR pathways.

Maternal diets enriched in olive oil regulate lipid metabolism and levels of PPARs and their coactivators in the fetal liver in a rat model of gestational diabetes mellitus.

In a rat model of gestational diabetes mellitus (GDM) programmed in the offspring of neonatal streptozotocin-induced (nSTZ) diabetic rats, lipids are accumulated in the fetal liver in a sex-dependent way. Here, we evaluated whether maternal diets enriched in olive oil in rats that will develop GDM ameliorate lipid metabolic impairments in the fetal livers. Pregnant offspring of control and nSTZ diabetic rats (F0) were fed a 6% olive oil-supplemented diet throughout the F1 gestation. We evaluated maternal metabolic parameters as well as lipid content, expression of lipid metabolizing enzymes and protein expression of PLIN2, PPARs and PPAR coactivators in the fetal livers. The offspring of nSTZ diabetic rats developed GDM regardless of the maternal treatment. Hypertriglyceridemia in GDM rats was prevented by the olive oil-enriched maternal treatment. In the livers of male fetuses of GDM rats, the maternal olive oil-supplemented diet prevented lipid overaccumulation and prevented the increase in PPARγ and PPARδ levels. In the livers of female fetuses of GDM rats, the maternal olive oil supplementation prevented the increase in PPARδ levels and the reduction in PGC1α levels, but did not prevent the reduced lipid content. Control and GDM rats showed a reduction of lipid metabolic enzymes in the fetal livers, which was associated with reduced levels of the PPAR coactivators PGC-1α and SRC-1 in males and of SRC-1 in females. These results suggest powerful effects of a maternal olive oil-supplemented diet in the fetal liver, possibly providing benefits in the fetuses and offspring from GDM rats.

Diet Enriched with Olive Oil Attenuates Placental Dysfunction in Rats with Gestational Diabetes Induced by Intrauterine Programming.

SCOPE: Offspring from rats with mild diabetes develop gestational diabetes mellitus (GDM). We tested the hypothesis that an olive oil-supplemented diet attenuates placental oxidative stress/inflammation, activation of mTOR signaling, and inhibition of peroxisome proliferator-activated receptor γ (PPARγ) and fetal overgrowth in GDM offspring from mild diabetic rats. METHODS AND RESULTS: Female offspring from rats with mild diabetes (group that developed GDM) and controls were fed with either a standard diet or a 6% olive oil-supplemented diet during pregnancy. On day 21 of pregnancy, plasma glucose levels in mothers and fetuses were increased in the GDM group independently of the diet. Fetal overgrowth and activation of placental mTOR signaling were partially prevented in the olive oil-treated GDM group. Placental PPARγ protein expression was decreased in GDM rats, independently of the diet. However, increases in placental lipoperoxidation, connective tissue growth factor, and matrix metalloproteinase 2 levels were prevented by the olive oil-enriched diet. CONCLUSION: Diets enriched with olive oil attenuate placental dysfunction and fetal overgrowth in rats with GDM induced by intrauterine programming.