Impact of erythrocyte long-chain omega-3 polyunsaturated fatty acid levels in early pregnancy on birth outcomes: findings from a Belgian cohort study.

OBJECTIVE: To examine the association between maternal erythrocyte long-chain omega-3 PUFA (n-3 LCPUFA), measured in early pregnancy, and pregnancy and birth outcomes. STUDY DESIGN: One hundred and eight healthy women with a singleton pregnancy were included. Erythrocyte fatty acids were analyzed using gas chromatography. Gestational length, birth anthropometric measures, and pregnancy-associated complications were collected from hospital medical records. RESULTS: We observed significant positive associations between maternal docosahexaenoic acid (DHA) levels (p = 0.024) and omega-3 index values (p = 0.021) and gestational length in adjusted linear regression models. Each point in maternal DHA level was associated with 2.19 days longer gestational duration (ß = 2.19; 95% CI 0.29-4.09). No consistent associations were found between n-3 PUFA levels and composite pregnancy outcome. CONCLUSION: These findings suggest that the gestational length is positively affected by maternal n-3 LCPUFA status as soon as the early stages of pregnancy.

Gut microbiota and osteoarthritis management: An expert consensus of the European society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO).

The prevalence of osteoarthritis (OA) increases not only because of longer life expectancy but also because of the modern lifestyle, in particular physical inactivity and diets low in fiber and rich in sugar and saturated fats, which promote chronic low-grade inflammation and obesity. Adverse alterations of the gut microbiota (GMB) composition, called microbial dysbiosis, may favor metabolic syndrome and inflammaging, two important components of OA onset and evolution. Considering the burden of OA and the need to define preventive and therapeutic interventions targeting the modifiable components of OA, an expert working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) to review the potential contribution of GMB to OA. Such a contribution is supported by observational or dietary intervention studies in animal models of OA and in humans. In addition, several well-recognized risk factors of OA interact with GMB. Lastly, GMB is a critical determinant of drug metabolism and bioavailability and may influence the response to OA medications. Further research targeting GMB or its metabolites is needed to move the field of OA from symptomatic management to individualized interventions targeting its pathogenesis.

Myoferlin Contributes to the Metastatic Phenotype of Pancreatic Cancer Cells by Enhancing Their Migratory Capacity through the Control of Oxidative Phosphorylation.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies with an overall survival of 5% and is the second cause of death by cancer, mainly linked to its high metastatic aggressiveness. Accordingly, understanding the mechanisms sustaining the PDAC metastatic phenotype remains a priority. In this study, we generated and used a murine in vivo model to select clones from the human Panc-1 PDAC cell line that exhibit a high propensity to seed and metastasize into the liver. We showed that myoferlin, a protein previously reported to be overexpressed in PDAC, is significantly involved in the migratory abilities of the selected cells. We first report that highly metastatic Panc-1 clones expressed a significantly higher myoferlin level than the corresponding low metastatic ones. Using scratch wound and Boyden's chamber assays, we show that cells expressing a high myoferlin level have higher migratory potential than cells characterized by a low myoferlin abundance. Moreover, we demonstrate that myoferlin silencing leads to a migration decrease associated with a reduction of mitochondrial respiration. Since mitochondrial oxidative phosphorylation has been shown to be implicated in the tumor progression and dissemination, our data identify myoferlin as a valid potential therapeutic target in PDAC.

Imbalance between Omega-6 and Omega-3 Polyunsaturated Fatty Acids in Early Pregnancy Is Predictive of Postpartum Depression in a Belgian Cohort.

While studies revealed that the omega-3 polyunsaturated fatty acids (n-3 PUFA) and their mediators would be able to regulate several biological processes involved into the development of postpartum depression (PPD), evidence from observational studies remains mixed. The aim of the present study was to investigate the association between maternal erythrocyte n-3 PUFA, measured in early pregnancy, and the risk of PPD. A Belgian cohort of 72 healthy women was screened. Erythrocyte fatty acids were analysed using gas chromatography. PPD was assessed using the Bromley Postnatal Depression Scale by phone interview one year after delivery. We observed a significant negative association between docosahexaenoic acid (DHA) levels and the risk of postpartum depression in the adjusted model (p = 0.034). Higher n-6/n-3 and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratios were significantly associated with an increased odds of PPD (p = 0.013 and p = 0.043, respectively). Women with an omega-3 index <5% had a 5-fold increased risk of depressive episode than did those with an omega-3 index ≥5% (OR 5.22 (95%CI 1.24-21.88)). A low n-3 PUFA status, alone and combined with high n-6 PUFA status, in early pregnancy was associated with a greater risk of PPD. Management of maternal n-3 PUFA deficiency can be a simple, safe and cost-effective strategy for the prevention of this major public health issue.

Importance of n-3 PUFA consumption during pregnancy: perception discrepancies between pregnant women and gynaecologists-obstetricians in Belgium.

OBJECTIVE: n-3 PUFA during pregnancy have been subject to intense research interest, but also much controversy, creating a situation of confusion among patients and health-care providers. The present study was carried out to explore knowledge, attitude and practices regarding n-3 PUFA in two independent populations of pregnant women and gynaecologists-obstetricians in Belgium and to assess the relationship between the pregnant women's attributes and their n-3 PUFA status measured by the omega-3 index. DESIGN: Cross-sectional study. Knowledge, attitude and practices were collected by self-administered questionnaires while laboratory data were available for each pregnant woman. SETTING: During the first antenatal hospital appointment (for the pregnant women) and by email (for the gynaecologists-obstetricians).ParticipantsWomen in early pregnancy (n 122) and gynaecologists-obstetricians (n 67). RESULTS: Marked discrepancies in perception were evidenced between the pregnant women and health-care providers. While 82 % of the women attached high importance to n-3 PUFA during pregnancy, only a third of the gynaecologists-obstetricians did. About 35 % of the women declared paying particular attention to their consumption of n-3 PUFA. After adjusting for sociodemographic characteristics, these positive dietary practices were significantly associated with higher omega-3 index (P=0·04). Overall, 43·3 % of professionals did not provide any information about n-3 PUFA to their pregnant patients and 46·3 % did not take any preventive actions. CONCLUSIONS: Evidence-based guidelines, refreshment training and communication tools are needed to improve awareness and clinical practices among caregivers regarding n-3 PUFA to benefit both mothers and their children.

Low omega-3 index values and monounsaturated fatty acid levels in early pregnancy: an analysis of maternal erythrocytes fatty acids.

BACKGROUND: It is unanimously recognized that the maternal nutritional status at the pregnancy onset influence both short-term and long-term health of the mother and offspring. Among several nutrients, LCPUFA, particularly from the omega-3 family, are of utmost importance. This study was carried out to determine fatty acids profile of maternal erythrocyte membranes in early pregnancy and to identify potential determinants impacting on this status. METHODS: A cohort of 122 healthy women with a singleton pregnancy was included. Fatty acids were analyzed using gas chromatography. Because of the lack of cutoff values, reference ranges were used to determine fatty acids categories. RESULTS: Of concern, our data revealed low monounsaturated and long-chain omega-3 fatty acid status in most participants. More than 75% of Belgian pregnant women exhibited Pal, AO and EPA levels as well as IOM3 values below the laboratory reference ranges. Higher DHA concentrations and IOM3 values were found among foreign-nationality participants, non-smokers and physically active women. With regard to dietary factors, omega-3 supplements and diet seem to be complementary since DHA from supplements (but not from diet) and EPA from diet (but not from supplements) were found to be associated with higher concentrations of DHA and EPA, respectively. CONCLUSIONS: Our study presents evidence demonstrating that the fatty acid status of most early pregnant women is far from being optimal based on the admitted general reference values. Clinicians should be advice to carefully evaluate and improve this status to guarantee the best possible outcome for both the mother and the baby.

In vivo PET/CT in a human glioblastoma chicken chorioallantoic membrane model: a new tool for oncology and radiotracer development.

UNLABELLED: For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken chorioallantoic membrane (CAM) provides a more rapid, low cost, and ethically sustainable alternative. For the first time, to our knowledge, we demonstrate the feasibility of in vivo PET and CT imaging in a U87 glioblastoma tumor model on chicken CAM, with the aim of applying this model for screening of novel PET tracers. METHODS: U87 glioblastoma cells were implanted on the CAM at day 11 after fertilization and imaged at day 18. A small-animal imaging cell was used to maintain incubation and allow anesthesia using isoflurane. Radiotracers were injected directly into the exposed CAM vasculature. Sodium (18)F-fluoride was used to validate the imaging protocol, demonstrating that image-degrading motion can be removed with anesthesia. Tumor glucose metabolism was imaged using (18)F-FDG, and tumor protein synthesis was imaged using 2-(18)F-fluoro-l-tyrosine. Anatomic images were obtained by contrast-enhanced CT, facilitating clear delineation of the tumor, delineation of tracer uptake in tumor versus embryo, and accurate volume measurements. RESULTS: PET imaging of tumor glucose metabolism and protein synthesis was successfully demonstrated in the CAM U87 glioblastoma model. Catheterization of CAM blood vessels facilitated dynamic imaging of glucose metabolism with (18)F-FDG and demonstrated the ability to study PET tracer uptake over time in individual tumors, and CT imaging improved the accuracy of tumor volume measurements. CONCLUSION: We describe the novel application of PET/CT in the CAM tumor model, with optimization of typical imaging protocols. PET imaging in this valuable tumor model could prove particularly useful for rapid, high-throughput screening of novel radiotracers.

Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase.

Sirtuins are homologues of the yeast transcriptional repressor Sir2p and are conserved from bacteria to humans. We report that human SIRT4 is localized to the mitochondria. SIRT4 is a matrix protein and becomes cleaved at amino acid 28 after import into mitochondria. Mass spectrometry analysis of proteins that coimmunoprecipitate with SIRT4 identified insulindegrading enzyme and the ADP/ATP carrier proteins, ANT2 and ANT3. SIRT4 exhibits no histone deacetylase activity but functions as an efficient ADP-ribosyltransferase on histones and bovine serum albumin. SIRT4 is expressed in islets of Langerhans and colocalizes with insulin-expressing beta cells. Depletion of SIRT4 from insulin-producing INS-1E cells results in increased insulin secretion in response to glucose. These observations define a new role for mitochondrial SIRT4 in the regulation of insulin secretion.