Browsing by Author "Pestana, Diogo"
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- Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDEPublication . Pestana, Diogo; Teixeira, Diana; Meireles, Manuela; Marques, Cláudia; Norberto, Sónia; Sá, Carla; Fernandes, Virgínia; Correia-Sá, Luísa; Faria, Ana; Guardão, Luísa; Guimarães, João T.; Cooper, Wendy N.; Sandovici, Ionel; Domingues, Valentina; Delerue-Matos, Cristina; Monteiro, Rosário; Constância, Miguel; Calhau, ConceiçãoEndocrine-disrupting chemicals such as p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), are bioaccumulated in the adipose tissue (AT) and have been implicated in the obesity and diabetes epidemic. Thus, it is hypothesized that p,p'-DDE exposure could aggravate the harm of an obesogenic context. We explored the effects of 12 weeks exposure in male Wistar rats' metabolism and AT biology, assessing a range of metabolic, biochemical and histological parameters. p,p'-DDE -treatment exacerbated several of the metabolic syndrome-accompanying features induced by high-fat diet (HF), such as dyslipidaemia, glucose intolerance and hypertension. A transcriptome analysis comparing mesenteric visceral AT (vAT) of HF and HF/DDE groups revealed a decrease in expression of nervous system and tissue development-related genes, with special relevance for the neuropeptide galanin that also revealed DNA methylation changes at its promoter region. Additionally, we observed an increase in transcription of dipeptidylpeptidase 4, as well as a plasmatic increase of the pro-inflammatory cytokine IL-1β. Our results suggest that p,p'-DDE impairs vAT normal function and effectively decreases the dynamic response to energy surplus. We conclude that p,p'-DDE does not merely accumulate in fat, but may contribute significantly to the development of metabolic dysfunction and inflammation. Our findings reinforce their recognition as metabolism disrupting chemicals, even in non-obesogenic contexts.
- Association between Elevated Iodine Intake and IQ among School Children in PortugalPublication . Carvalho, Irene P.; Peixoto, Bruno; Caldas, José Carlos; Costa, Ana; Silva, Sofia; Moreira, Bárbara; Almeida, Agostinho; Moreira-Rosário, André; Guerra, António; Delerue-Matos, Cristina; Sintra, Diana; Pestana, Diogo; Pinto, Edgar; Mendes, Francisca Castro; Martins, Inês; Leite, João Costa; Fontoura, Manuel; Maia, Maria Luz; Queirós, Pedro; Moreira, Roxana; Leal, Sandra; Norberto, Sónia; Costa, Vera; Fernandes, Virgínia Cruz; Keating, Elisa; Azevedo, Luís; Calhau, ConceiçãoThe goal of this work was to examine whether elevated iodine intake was associated with adverse effects on IQ among school-age children in Portugal. In a representative sample of children from the north of the country, IQ percentiles by age (assessed with Raven’s Colored Progressive Matrices) were dichotomized to <50 (“below-average” IQs) and ≥50. Morning urine iodine concentrations, corrected for creatinine, were dichotomized to <250 µg/g and ≥250 µg/g, according to the European Commission/Scientific Committee on Food’s tolerable upper level of daily iodine intake for young children. Data were examined with Chi-square tests, logistic regression, and GLM univariate analysis. The sample (N = 1965) was classified as generally iodine-adequate (median urinary iodine concentration = 129 µg/L; median iodine-to-creatinine ratio = 126 µg/g) according to the WHO’s criteria. A greater proportion of children in the ≥250 µg/g group had below-average IQs, compared to children with less than 250 µg/g (p = 0.037), despite a sizable (though non-significant) proportion of children in the less-than-250 µg/g group also presenting below-average IQs, at the bottom of the iodine distribution (<50 µg/g). The proportion of below-average IQs increased with increasingly elevated iodine concentrations (p = 0.047). The association remained significant after the adjustment for confounders, with the elevated iodine group showing increased odds of having below-average IQs when compared with the non-elevated iodine group (OR 1.55; 95% CI 1.11–2.17; p = 0.011). Consistently, the former group presented a lower mean IQ than the latter (p = 0.006). High iodine intake was associated with lower IQs even in a population classified as iodine-adequate. These results bear on child cognition and on initiatives involving iodine supplementation
- Association between elevated iodine intake and IQ among school children in PortugalPublication . Carvalho, Irene P.; Peixoto, Bruno; Caldas, José Carlos; Costa, Ana; Silva, Sofia; Moreira, Bárbara; Almeida, Agostinho; Moreira-Rosário, André; Guerra, António; Delerue-Matos, Cristina; Sintra, Diana; Pestana, Diogo; Pinto, Edgar; Mendes, Francisca Castro; Martins, Inês; Leite, João Costa; Fontoura, Manuel; Maia, Maria Luz; Queirós, Pedro; Moreira, Roxana; Leal, Sandra; Norberto, Sónia; Costa, Vera; Fernandes, Virgínia Cruz; Keating, Elisa; Azevedo, Luís; Calhau, ConceiçãoThe goal of this work was to examine whether elevated iodine intake was associated with adverse effects on IQ among school-age children in Portugal. In a representative sample of children from the north of the country, IQ percentiles by age (assessed with Raven’s Colored Progressive Matrices) were dichotomized to <50 (“below-average” IQs) and ≥50. Morning urine iodine concentrations, corrected for creatinine, were dichotomized to <250 µg/g and ≥250 µg/g, according to the European Commission/Scientific Committee on Food’s tolerable upper level of daily iodine intake for young children. Data were examined with Chi-square tests, logistic regression, and GLM univariate analysis. The sample (N = 1965) was classified as generally iodine-adequate (median urinary iodine concentration = 129 µg/L; median iodine-to-creatinine ratio = 126 µg/g) according to the WHO’s criteria. A greater proportion of children in the ≥250 µg/g group had below-average IQs, compared to children with less than 250 µg/g (p = 0.037), despite a sizable (though non-significant) proportion of children in the less-than-250 µg/g group also presenting below-average IQs, at the bottom of the iodine distribution (<50 µg/g). The proportion of below-average IQs increased withncreasingly elevated iodine concentrations (p = .047). The association remained significant after the adjustment for confounders, with the elevated iodine group showing increased odds of having below-average IQs when compared with the non-elevated iodine group (OR 1.55; 95% CI 1.11–2.17; p = 0.011). Consistently, the former group presented a lower mean IQ than the latter (p = 0.006). High iodine intake was associated with lower IQs even in a population classified as iodine-adequate. These results bear on child cognition and on initiatives involving iodine supplementation.
- Association of 3-Phenoxybenzoic Acid Exposure during Pregnancy with Maternal Outcomes and Newborn Anthropometric Measures: Results from the IoMum Cohort StudyPublication . Guimarães, Juliana; Bracchi, Isabella; Pinheiro, Cátia; Moreira, Nara Xavier; Coelho, Cláudia Matta; Pestana, Diogo; Prucha, Maria do Carmo; Martins, Cristina; Domingues, Valentina F.; Delerue-Matos, Cristina; Dias, Cláudia C.; Azevedo, Luís Filipe R.; Calhau, Conceição; Leite, João Costa; Ramalho, Carla; Keating, Elisa; Fernandes, Virgínia CruzThe aims of this study were to characterize the exposure of pregnant women living in Portugal to 3-phenoxybenzoic acid (3-PBA) and to evaluate the association of this exposure with maternal outcomes and newborn anthropometric measures. We also aimed to compare exposure in summer with exposure in winter. Pregnant women attending ultrasound scans from April 2018 to April 2019 at a central hospital in Porto, Portugal, were invited to participate. Inclusion criteria were: gestational week between 10 and 13, confirmed fetal vitality, and a signature of informed consent. 3-PBA was measured in spot urine samples by gas chromatography with mass spectrometry (GC-MS). The median 3-PBA concentration was 0.263 (0.167; 0.458) μg/g creatinine (n = 145). 3-PBA excretion was negatively associated with maternal pre-pregnancy body mass index (BMI) (p = 0.049), and it was higher during the summer when compared to winter (p < 0.001). The frequency of fish or yogurt consumption was associated positively with 3-PBA excretion, particularly during the winter (p = 0.002 and p = 0.015, respectively), when environmental exposure is low. Moreover, 3-PBA was associated with levothyroxine use (p = 0.01), a proxy for hypothyroidism, which could be due to a putative 3-PBA—thyroid hormone antagonistic effect. 3-PBA levels were not associated with the anthropometric measures of the newborn. In conclusion, pregnant women living in Portugal are exposed to 3-PBA, particularly during summer, and this exposure may be associated with maternal clinical features.
- Brominated flame retardants effect in MCF-7 cells: Impact on vitamin D pathwayPublication . Sousa, Sara; Maia, Maria Luz; Pestana, Diogo; Teixeira, Diana; Ângelo-Dias, Miguel; Martins, Catarina; Borrego, Luís Miguel; Delerue-Matos, Cristina; Calhau, Conceição; Domingues, Valentina; Faria, AnaBrominated flame retardants (BFRs) are persistent environmental pollutants, allowing a constant human exposure which carries several health risks, including the occurrence of breast cancer and vitamin D deficiency. Vitamin D inhibits cell growth and is negatively associated with breast cancer risk. The effect of BFRs in breast cancer and vitamin D pathway is still poorly understood. MCF-7 cells were treated with hexabromocyclododecane (HBCD), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), hexabromobenzene (HBB) and pentabromotoluene (PBT) using short and long-term exposure protocols. Viability, proliferation, migration, cell cycle and gene expression were assessed. Gene expression of hVDBP and hCYP2R1 was also evaluated in hepatocytes. Long-term exposure of MCF-7 cells to HBB increased cell proliferation and migration, consequently increasing MMP-9 expression. The vitamin D pathway was also altered by BFRs: cells appeared less prepared to activate and transport vitamin D and the signaling, action and inactivation mechanisms were diminished in the presence of BFRs. Untreated MCF-7 cells showed cell cycle arrest in phase G0/G1 in the presence of activated vitamin D. However, when MCF-7 cells were exposed to BFRs, cell cycle was arrested in phase G2/M, possibly due to DNA damage. Nonetheless, calcitriol seems to be able to mitigate the effect of some BFRs exposure, e.g. PBT
- Effects of Environmental Organochlorine Pesticides on Human Breast Cancer: Putative Involvement on Invasive Cell AbilityPublication . Pestana, Diogo; Teixeira, Diana; Faria, Ana; Domingues, Valentina; Monteiro, Rosário; Calhau, ConceiçãoHuman exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p′-dichlorodiphenyltrichloroethane (o,p′-DDT), and its metabolites p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), and p,p′-dichlorodiphenyldichloroethane (p,p′-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p′-DDT, p,p′-DDE, and p,p′-DDD (50–1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology.
- Essential trace elements status in portuguese pregnant women and their association with maternal and neonatal outcomes: A prospective study from the IoMum CohortPublication . Bracchi, Isabella; Guimarães, Juliana; Rodrigues, Catarina; Azevedo, Rui; Coelho, Cláudia Matta; Pinheiro, Cátia; Morais, Juliana; Barreiros-Mota, Inês; Fernandes, Virgínia Cruz; Delerue-Matos, Cristina; Pinto, Edgar; Moreira-Rosário, André; Azevedo, Luís Filipe Ribeiro de; Dias, Cláudia Camila; Lima, Jorge; Sapinho, Inês; Ramalho, Carla; Calhau, Conceição; Leite, João Costa; Almeida, Agostinho; Pestana, Diogo; Keating, ElisaCobalt (Co), copper (Cu), manganese (Mn), molybdenum (Mo), and zinc (Zn) are essential trace elements (ETEs) important in cellular chemical reactions and antioxidant defense. Ingestion of ETEs during pregnancy is crucial but their role in specific pregnancy outcomes is largely unknown. This study aimed to quantify urinary levels of these ETEs in pregnancy and to evaluate their role in pregnancy health. First trimester pregnant women of Porto and Lisbon regions provided a urine sample, and sociodemographic and lifestyle data. Clinical data were obtained from clinical records. Urinary ETEs were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Our results show that having urinary Zn levels above the 50th percentile (P50) increases the risk of pre-eclampsia (PE). On the other hand, urinary Zn levels above the P50 decreased the risk of being born with head circumference small for gestational age but it increased the risk having length small for gestational age at birth. This study may provide valuable information for public health policies related to prenatal nutrition, while informing future efforts to de-fine urinary reference intervals for ETEs in pregnant women
- Impact of brominated flame retardants on lipid metabolism: An in vitro approachPublication . Maia, Maria Luz; Sousa, Sara; Pestana, Diogo; Faria, Ana; Teixeira, Diana; Delerue-Matos, Cristina; Domingues, Valentina; Calhau, ConceiçãoBrominated flame retardants (BFRs) are chemicals employed to lower the flammability of several objects. These endocrine disruptor chemicals are lipophilic and persistent in the environment. Due to these characteristics some have been restricted or banned by the European Union, and replaced by several new chemicals, the novel BFRs (NBFRs). BFRs are widely detected in human samples, such as adipose tissue and some were linked with altered thyroid hormone levels, liver toxicity, diabetes and metabolic syndrome in humans. However, the disturbance in lipid metabolism caused by BFRs with emphases to NBFRs remains poorly understood. In this study, we used a pre-adipocyte (3T3-L1) cell line and a hepatocyte (HepG2) cell line to investigate the possible lipid metabolism disruption caused by four BFRs: hexabromobenzene (HBB), pentabromotoluene (PBT), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and hexabromocyclododecane (HBCD). For that purpose, proliferation and Oil Red O assays, as well as, medium fatty acids profile evaluation using Gas chromatography and RNA extraction for quantitative RT-PCR assays were performed. We detected a significant reduction in the proliferation of preadipocytes and an increased lipid accumulation during differentiation caused by HBB. This BFR also lead to a significant increased expression of IL-1β and decreased expression of PGC-1α and adiponectin. Nevertheless, PBT, TBB and HBCD show to increase lipid accumulation in hepatocytes. PBT also display a significant increase of PPARγ gene expression. Lipid accumulation in the cells can occur by diverse mechanisms depending on the BFR. These results highlight the importance of endocrine disruptor compounds in obesity etiopathogeny.
- Inflammatory and Cardiometabolic Risk on Obesity: Role of Environmental XenoestrogensPublication . Teixeira, Diana; Pestana, Diogo; Santos, Cristina; Correia-Sá, Luísa; Marques, Cláudia; Norberto, Sónia; Meireles, Manuela; Faria, Ana; Silva, Ricardo; Faria, Gil; Sá, Carla; Freitas, Paula; Taveira-Gomes, António; Domingues, Valentina; Delerue-Matos, Cristina; Calhau, Conceição; Monteiro, RosárioContext: Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown. Objective: The objective of the study was to investigate the levels of XEs in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state. Design and Participants: We evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m2) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed, according to menopausal status (73 pre- and 48 postmenopausal). Levels of XEs were determined by gas chromatography with electron-capture detection. Anthropometric and biochemical data were collected prior to surgery. Adipocyte size was determined on tissue sections obtained during surgery. Results: Our data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk. Conclusions: Our findings point toward a different distribution of XE between plasma and AT in pre- and postmenopausal women, and reveal the association between XEs on the development of metabolic abnormalities in obese premenopausal women
- Iodine knowledge is associated with iodine status in Portuguese pregnant women: results from the IoMum cohort studyPublication . Pinheiro, Cátia; Moreira, Nara Xavier; Ferreira, Pedro; Coelho, Cláudia Matta; Guimarães, Juliana; Pereira, Gonçalo; Cortez, Alice; Bracchi, Isabella; Pestana, Diogo; Mota, Inês Barreiros; Prucha, Carmo; Martins, Cristina; Ribeiro, Célia Alves; Pinto, Edgar; Almeida, Agostinho; Delerue-Matos, Cristina; Montenegro, Nuno; Dias, Cláudia Camila; Moreira-Rosário, André; Azevedo, Luís Filipe; Brantsæter, Anne-Lise; Ramalho, Carla; Fernandes, Virgínia Cruz; Leite, João Costa; Calhau, Conceição; Keating, ElisaLack of knowledge about iodine has been suggested as a risk factor for iodine deficiency in pregnant women, but no studies have addressed this issue in Portugal. So, the aim of this study was to investigate iodine knowledge among Portuguese pregnant women and its association with iodine status. IoMum, a prospective observational study, included 485 pregnant women recruited at Centro Hospitalar e Universitário de S. João, Porto, between the 10th and 13th gestational weeks. Partial scores for knowledge on iodine importance, on iodine food sources or on iodised salt were obtained through the application of a structured questionnaire. Then, a total iodine knowledge score was calculated and grouped into low, medium and high knowledge categories. Urinary iodine concentration (UIC) was measured in spot urine samples by inductively coupled plasma MS. Of the pregnant women, 54 % correctly recognised iodine as important to neurocognitive development, 32 % were unable to identify any iodine-rich food and 71 % presented lack of knowledge regarding iodised salt. Of the women, 61 % had a medium total score of iodine knowledge. Knowledge on iodine importance during pregnancy was positively associated with iodine supplementation and also with UIC. Nevertheless, median UIC in women who correctly recognised the importance of iodine was below the cut-off for adequacy in pregnancy (150 µg/l). In conclusion, knowledge on iodine importance is positively associated with iodine status. Despite this, recognising iodine importance during pregnancy may not be sufficient to ensure iodine adequacy. Literacy-promoting actions are urgently needed to improve iodine status in pregnancy.