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1.
Nutrients ; 16(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38732507

RESUMO

INTRODUCTION: Pre-pregnancy obesity is a significant public health concern with profound implications for maternal and child health. The burgeoning evidence suggests that maternal obesity prior to conception is intricately linked with an increased risk of gestational complications, as well as with adverse neonatal outcomes. Furthermore, the long and short-term health of offspring, including the risk of early motor development impairment, obesity, and metabolic syndrome in childhood and adulthood, may be adversely affected as well. Addressing pre-pregnancy obesity is critical for improving overall maternal and child health outcomes, and therefore, the aim of this study was to evaluate the connections linking pre-pregnancy obesity with infants' motor development within the first twelve months of infants' lives. MATERIAL AND METHODS: This study included 200 mother-infant pairs divided into two groups based on their pre-pregnancy body mass index values. To assess infants' early motor development, we used the Alberta Infant Motor Scale (AIMS) and evaluated the parameters of infants' early motor development at the ages of three, six, nine, and twelve months. RESULTS: Pre-pregnancy overweight/obesity was significantly associated with excessive gestational weight gain (p < 0.001), fetal macrosomia (p = 0.022), and a family history of diabetes and cardiovascular diseases (p = 0.048 and p = 0.041, respectively), as well as with all observed parameters of early motor development at the ages of three, six, nine, and twelve months: AIMS 3 months total (p < 0.001), AIMS 6 months total (p < 0.001), AIMS 9 months total (p < 0.001), and AIMS 12 months total (p < 0.001). Furthermore, pre-pregnancy overweight/obesity was a significant predictor for AIMS 6 months total (p = 0.043) and AIMS 6 months supination (p = 0.017). CONCLUSIONS: Pre-pregnancy obesity is a critical determinant of pregnancy outcomes and offspring early motor development, with possible far-reaching implications for children's long-term well-being. Addressing this issue requires a comprehensive approach that includes preconception weight management, targeted interventions during the pregnancy and postpartum periods, and ongoing research to better understand the underlying mechanisms and develop effective strategies for prevention and management.


Assuntos
Desenvolvimento Infantil , Obesidade , Humanos , Feminino , Gravidez , Lactente , Adulto , Obesidade/epidemiologia , Masculino , Índice de Massa Corporal , Ganho de Peso na Gestação , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/etiologia , Complicações na Gravidez/epidemiologia , Recém-Nascido , Obesidade Materna/epidemiologia , Destreza Motora , Fatores de Risco
2.
Pediatr Obes ; 19(6): e13120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38590200

RESUMO

Maternal obesity is a well-known risk factor for developing premature obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes in the progeny. The development of white adipose tissue is a dynamic process that starts during prenatal life: fat depots laid down in utero are associated with the proportion of fat in children later on. How early this programming takes place is still unknown. However, recent evidence shows that mesenchymal stem cells (MSC), the embryonic adipocyte precursor cells, show signatures of the early setting of an adipogenic committed phenotype when exposed to maternal obesity. This review aims to present current findings on the cellular adaptations of MSCs from the offspring of women with obesity and how the metabolic environment of MSCs could affect the early commitment towards adipocytes. In conclusion, maternal obesity can induce early programming of fetal adipose tissue by conditioning MSCs. These cells have higher expression of adipogenic markers, altered insulin signalling and mitochondrial performance, compared to MSCs of neonates from lean pregnancies. Fetal MSCs imprinting by maternal obesity could help explain the increased risk of childhood obesity and development of further noncommunicable diseases.


Assuntos
Células-Tronco Mesenquimais , Obesidade Materna , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Gravidez , Obesidade Materna/metabolismo , Tecido Adiposo , Obesidade Infantil , Adipogenia/fisiologia , Recém-Nascido , Adipócitos
3.
Obesity (Silver Spring) ; 32(5): 979-988, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600046

RESUMO

OBJECTIVE: This study explores the impact of maternal pre-pregnancy BMI on infant neurodevelopment at 24 months in low-income Latino families. It also investigates whether infant diet mediates this relationship. METHODS: Latino mother-infant pairs (n = 163) were enrolled at 1 month post partum and were followed for 2 years, with assessments at 6-month intervals. Maternal pre-pregnancy anthropometrics were self-reported at baseline, and child neurodevelopment was assessed at 24 months using the Bayley Scales of Infant Development. Diet quality of infants was measured using the Healthy Eating Index (HEI)-2015 and HEI-Toddlers-2020 scores at multiple time points. Mediation and regression models that adjust for maternal factors were used to examine the associations. RESULTS: Pre-pregnancy BMI showed significant negative associations with child cognitive scores (ß = -0.1, 95% CI: -0.2 to -0.06, p < 0.001) and language scores (ß = -0.1, 95% CI: -0.2 to -0.03, p = 0.01) at 24 months. Infant HEI-2015 scores at 24 months partly mediated these associations, explaining 23% and 30% of the total effect on cognitive and language subscales, respectively. No specific dietary components in infants mediated the relationship, except for the total HEI-2015 score. CONCLUSIONS: Managing maternal obesity pre-pregnancy is crucial for improving infant neurodevelopmental outcomes, especially in low-income Latino families. Promoting healthy weight and enhancing infant diet quality can enhance neurodevelopment in these populations.


Assuntos
Índice de Massa Corporal , Desenvolvimento Infantil , Hispânico ou Latino , Obesidade Materna , Adulto , Feminino , Humanos , Lactente , Masculino , Gravidez , Cognição , Dieta , Dieta Saudável , Hispânico ou Latino/estatística & dados numéricos , Mães/psicologia , Pobreza
4.
Nutrients ; 16(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38613062

RESUMO

The adverse influence of maternal obesity on offspring metabolic health throughout the life-course is a significant public health challenge with few effective interventions. We examined if black bean powder (BBP) supplementation to a high-calorie maternal pregnancy diet or a postnatal offspring diet could offer protection against the metabolic programming of metabolic disease risk in adult offspring. Female Sprague Dawley rats were randomly assigned to one of three diets (n = 10/group) for a 3-week pre-pregnancy period and throughout gestation and lactation: (i) a low-caloric control diet (CON); (ii) a high-caloric obesity-inducing diet (HC); or (iii) the HC diet with 20% black bean powder (HC-BBP). At weaning [postnatal day (PND) 21], one male pup from each dam was weaned onto the CON diet throughout the postnatal period until adulthood (PND120). In addition, a second male from the HC group only was weaned onto the CON diet supplemented with BBP (CON-BBP). Thus, based on the maternal diet exposure and offspring postnatal diet, four experimental adult offspring groups were compared: CON/CON, HC/CON, HC-BPP/CON, and HC/CON-BBP. On PND120, blood was collected for biochemical analysis (e.g., lipids, glycemic control endpoints, etc.), and livers were excised for lipid analysis (triglycerides [TG] and cholesterol) and the mRNA/protein expression of lipid-regulatory targets. Compared with the CON/CON group, adult offspring from the HC/CON group exhibited a higher (p < 0.05) body weight (BW) (682.88 ± 10.67 vs. 628.02 ± 16.61 g) and hepatic TG (29.55 ± 1.31 vs. 22.86 ± 1.85 mmol/g). Although maternal BBP supplementation (HC-BBP/CON) had little influence on metabolic outcomes, the consumption of BBP in the postnatal period (HC/CON-BBP) lowered hepatic TG and cholesterol compared with the other treatment groups. Reduced hepatic TG in the HC/CON-BBP was likely associated with lower postnatal BW gain (vs. HC/CON), lower mRNA and protein expression of hepatic Fasn (vs. HC/CON), and lower serum leptin concentration (vs. CON/CON and HC groups). Our results suggest that the postnatal consumption of a black-bean-powder-supplemented diet may protect male rat offspring against the programming of obesity and dyslipidemia associated with maternal obesity. Future work should investigate the bioactive fraction of BBP responsible for the observed effect.


Assuntos
Dislipidemias , Obesidade Materna , Humanos , Gravidez , Adulto , Feminino , Masculino , Ratos , Animais , Pós , Filhos Adultos , Ratos Sprague-Dawley , Obesidade/etiologia , Obesidade/prevenção & controle , Dislipidemias/etiologia , Dislipidemias/prevenção & controle , Colesterol , RNA Mensageiro , Lipídeos
5.
BMC Pregnancy Childbirth ; 24(1): 297, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649888

RESUMO

BACKGROUND: Maternal overweight/obesity and excessive gestational weight gain (GWG) are frequently reported to be risk factors for obesity and other metabolic disorders in offspring. Cord blood metabolites provide information on fetal nutritional and metabolic health and could provide an early window of detection of potential health issues among newborns. The aim of the study was to explore the impact of maternal prepregnancy overweight/obesity and excessive GWG on cord blood metabolic profiles. METHODS: A case control study including 33 pairs of mothers with prepregnancy overweight/obesity and their neonates, 30 pairs of mothers with excessive GWG and their neonates, and 32 control mother-neonate pairs. Untargeted metabolomic profiling of umbilical cord blood samples were performed using UHPLC‒MS/MS. RESULTS: Forty-six metabolites exhibited a significant increase and 60 metabolites exhibited a significant reduction in umbilical cord blood from overweight and obese mothers compared with mothers with normal body weight. Steroid hormone biosynthesis and neuroactive ligand‒receptor interactions were the two top-ranking pathways enriched with these metabolites (P = 0.01 and 0.03, respectively). Compared with mothers with normal GWG, in mothers with excessive GWG, the levels of 63 metabolites were increased and those of 46 metabolites were decreased in umbilical cord blood. Biosynthesis of unsaturated fatty acids was the most altered pathway enriched with these metabolites (P < 0.01). CONCLUSIONS: Prepregnancy overweight and obesity affected the fetal steroid hormone biosynthesis pathway, while excessive GWG affected fetal fatty acid metabolism. This emphasizes the importance of preconception weight loss and maintaining an appropriate GWG, which are beneficial for the long-term metabolic health of offspring.


Assuntos
Sangue Fetal , Ganho de Peso na Gestação , Metaboloma , Humanos , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Estudos de Casos e Controles , Gravidez , Adulto , Recém-Nascido , Metaboloma/fisiologia , Sobrepeso/sangue , Obesidade/sangue , Complicações na Gravidez/sangue , Metabolômica/métodos , Obesidade Materna/sangue
6.
Front Public Health ; 12: 1346900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38544732

RESUMO

Background: Maternal obesity is associated with an increased risk of large-for-gestational-age births and childhood obesity. However, evidence on its potential associations with long-term offspring body composition remains limited. This prospective cohort study examined associations between maternal body mass index (BMI) during pregnancy and body composition in the young adult offspring. Methods: Participants were the offspring from a birth cohort in Chiang Mai (Thailand). Maternal BMI was assessed at the first antenatal clinic visit (≤24 weeks of gestation) in 1989-1990. In 2010-2011, we followed up the offspring at approximately 20 years of age, assessing their body composition using whole-body dual-energy X-ray absorptiometry (DXA) scans. Associations between maternal BMI and offspring body composition were explored using unadjusted and adjusted analyses. Results: We assessed 391 young adults (55% were females). Higher maternal BMI was associated with increased offspring fat mass and lean mass. In adjusted analyses, offspring of mothers with overweight/obesity exhibited total body fat percentages 1.5 (95% CI 0.1, 2.9; p = 0.032) and 2.3 (95% CI 0.2, 4.5; p = 0.036) percentage points higher than offspring of normal-weight and underweight mothers, respectively. Fat mass index was similarly higher: 0.9 kg/m2 (95% CI 0.3, 1.5 kg/m2; p = 0.002) and 1.4 kg/m2 (95% CI 0.5, 2.3 kg/m2; p = 0.002), respectively. However, no differences in visceral adiposity were detected. Conclusion: Higher maternal BMI during pregnancy was associated with increased adiposity in young adult offspring. Our findings suggest that the cross-generational transmission of maternal obesity-related traits is associated with increased offspring adiposity in the long term.


Assuntos
Obesidade Materna , Obesidade Infantil , Adulto Jovem , Feminino , Humanos , Criança , Gravidez , Masculino , Sobrepeso , Estudos Prospectivos , Filhos Adultos , Composição Corporal
7.
J Nutr Biochem ; 128: 109625, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521130

RESUMO

Maternal obesity might induce obesity and metabolic alterations in the progeny. The study aimed to determine the effect of supplementing obese mothers with Mel (Mel) on thermogenesis and inflammation. C57BL/6 female mice (mothers) were fed from weaning to 12 weeks control diet (C, 17% kJ as fat) or a high-fat diet (HF, 49% kJ as fat) and then matted with male mice fed the control diet. Melatonin (10 mg/kg daily) was supplemented to mothers during gestation and lactation, forming the groups C, CMel, HF, and HFMel (n = 10/group). Twelve-week male offspring were studied (plasma biochemistry, immunohistochemistry, protein, and gene expressions at the hypothalamus - Hyp, subcutaneous white adipose tissue - sWAT, and interscapular brown adipose tissue - iBAT). Comparing HFMel vs. HF offspring, fat deposits and plasmatic proinflammatory markers decreased. Also, HFMel showed decreased Hyp proinflammatory markers and neuropeptide Y (anabolic) expression but improved proopiomelanocortin (catabolic) expression. Besides, HFMel sWAT adipocytes changed to a beige phenotype with-beta-3 adrenergic receptor and uncoupling protein-1 activation, concomitant with browning genes activation, triggering the iBAT thermogenic activity. In conclusion, compelling evidence indicated the beneficial effects of supplementing obese mothers with Mel on the health of their mature male offspring. Mel led to sWAT browning-related gene enhancement, increased iBAT thermogenis, and mitigated hypothalamic inflammation. Also, principal component analysis of the data significantly separated the untreated obese mother progeny from the progeny of treated obese mothers. If confirmed in humans, the findings encourage a future guideline recommending Mel supplementation during pregnancy and breastfeeding.


Assuntos
Dieta Hiperlipídica , Suplementos Nutricionais , Hipotálamo , Inflamação , Melatonina , Camundongos Endogâmicos C57BL , Obesidade Materna , Termogênese , Animais , Termogênese/efeitos dos fármacos , Feminino , Melatonina/farmacologia , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Masculino , Gravidez , Obesidade Materna/metabolismo , Inflamação/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Fenômenos Fisiológicos da Nutrição Materna , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética
8.
Cell Mol Life Sci ; 81(1): 151, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526599

RESUMO

Obesity and gestational diabetes (GDM) impact fetal growth during pregnancy. Iron is an essential micronutrient needed for energy-intense feto-placental development, but if mis-handled can lead to oxidative stress and ferroptosis (iron-dependent cell death). In a mouse model showing maternal obesity and glucose intolerance, we investigated the association of materno-fetal iron handling and placental ferroptosis, oxidative damage and stress signalling activation with fetal growth. Female mice were fed a standard chow or high fat, high sugar (HFHS) diet during pregnancy and outcomes were measured at day (d)16 or d19 of pregnancy. In HFHS-fed mice, maternal hepcidin was reduced and iron status maintained (tissue iron levels) at both d16 and d19. However, fetal weight, placental iron transfer capacity, iron deposition, TFR1 expression and ERK2-mediated signalling were reduced and oxidative damage-related lipofuscin accumulation in the placenta was increased in HFHS-fed mice. At d19, whilst TFR1 remained decreased, fetal weight was normal and placental weight, iron content and iron transporter genes (Dmt1, Zip14, and Fpn1) were reduced in HFHS-fed mice. Furthermore, there was stress kinase activation (increased phosphorylated p38MAPK, total ERK and JNK) in the placenta from HFHS-fed mice at d19. In summary, a maternal HFHS diet during pregnancy impacts fetal growth trajectory in association with changes in placental iron handling, ferroptosis and stress signalling. Downregulation of placental iron transporters in HFHS mice may protect the fetus from excessive oxidative iron. These findings suggest a role for alterations in placental iron homeostasis in determining perinatal outcomes of pregnancies associated with GDM and/or maternal obesity.


Assuntos
Ferroptose , Obesidade Materna , Humanos , Gravidez , Feminino , Animais , Camundongos , Ferro , Peso Fetal , Placenta , Feto , Dieta Hiperlipídica/efeitos adversos
9.
Am J Physiol Renal Physiol ; 326(5): F727-F736, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38511219

RESUMO

Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.


Assuntos
Injúria Renal Aguda , Rim , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão , Animais , Masculino , Feminino , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/patologia , Rim/fisiopatologia , Rim/patologia , Rim/metabolismo , Fatores Sexuais , Obesidade/complicações , Obesidade/fisiopatologia , Dieta Hiperlipídica , Gravidez , Lipocalina-2/metabolismo , Obesidade Materna/metabolismo , Obesidade Materna/complicações , Obesidade Materna/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal , Camundongos , Fatores de Risco , Modelos Animais de Doenças , Biomarcadores/sangue
10.
CMAJ ; 196(8): E250-E259, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38438153

RESUMO

BACKGROUND: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. METHODS: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. RESULTS: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35-1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44-2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83-2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. INTERPRETATION: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term.


Assuntos
Obesidade Materna , Natimorto , Gravidez , Feminino , Humanos , Lactente , Natimorto/epidemiologia , Estudos Retrospectivos , Obesidade/epidemiologia , Fatores de Risco
11.
Early Hum Dev ; 191: 105990, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38518425

RESUMO

BACKGROUND: Maternal obesity influences birth weight and newborn adiposity. Fetal fractional limb volume has recently been introduced as a useful parameter for the proxy of fetal adiposity. However, the association between maternal adiposity and the growth of fetal fractional limb volume has not been examined. AIMS: To investigate the association of maternal pre-pregnancy BMI with the growth of fetal fractional limb volume. STUDY DESIGN: Prospective cohort study. SUBJECTS: Women with singleton uncomplicated pregnancies enrolled between July 2017 and June 2020. OUTCOME MEASURES: Fetal fractional limb volume was assessed between 20 and 40 weeks' gestation, measured as cylindrical limb volume based on 50 % of the total diaphysis length. The measured fractional limb volume at each gestational week were converted to z-scores based on a previous report. The association between pre-pregnancy BMI and fetal fractional limb volume was examined. Maternal age, parity, gestational weight gain and fetal sex were considered as potential confounding variables. RESULTS: Ultrasound scans of 455 fractional arm volume and thigh volume were obtained. Fractional limb volume increased linearly until the second trimester of gestation, then increased exponentially in the third trimester. Maternal pre-pregnancy BMI was significantly correlated with z-scores of fractional arm volume and thigh volume across gestation. The post-hoc analysis showed the association between pre-pregnancy BMI and fractional arm volume was significant especially between 34 and 40 weeks. CONCLUSIONS: Maternal obesity influences the growth pattern of fetal fractional limb volume. Fractional arm volume may potentially provide a useful surrogate marker of fetal nutritional status in late gestation.


Assuntos
Obesidade Materna , Recém-Nascido , Gravidez , Feminino , Humanos , Estudos Prospectivos , Ultrassonografia Pré-Natal , Peso ao Nascer , Terceiro Trimestre da Gravidez , Idade Gestacional , Obesidade/epidemiologia
12.
J Dev Orig Health Dis ; 15: e4, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38500346

RESUMO

The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln. Epi significantly increased the Pgc-1α protein in the MO group of offspring at 110 pnd (p < 0.036, MO vs. MO+Epi), while at 245 pnd, Epi increased Fndc5/irisin mRNA expression in the MO+Epi group versus the MO group (p = 0.006).No differences were detected in Fndc5/irisin, Ucp3 or Sln mRNA or protein levels (including Pgc-1α mRNA) in the offspring at 110 pnd or in Pgc-1α, Ucp3, or Sln mRNA or protein levels (including Fndc5/irisin protein) at 245 pnd among the experimental groups. In conclusion, (-)-epicatechin treatment increased Fndc5/irisin mRNA expression and Pgc-α protein levels in the gastrocnemius muscle of offspring at postnatal days 110 and 245. Furthermore, it is suggested that the flavonoid effect in a model of obesity and its impact on thermogenesis in skeletal muscle are regulated by a different pathway than Fndc5/irisin.


Assuntos
Catequina , Obesidade Materna , Humanos , Gravidez , Ratos , Masculino , Feminino , Animais , Catequina/farmacologia , Fibronectinas/genética , Fibronectinas/metabolismo , Fibronectinas/farmacologia , Músculo Esquelético/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade Materna/metabolismo , RNA Mensageiro/genética
13.
CNS Neurosci Ther ; 30(3): e14700, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38544384

RESUMO

BACKGROUND: Perinatal exposure to maternal obesity predisposes offspring to develop obesity later in life. Immune dysregulation in the hypothalamus, the brain center governing energy homeostasis, is pivotal in obesity development. This study aimed to identify key candidate genes associated with the risk of offspring obesity in maternal obesity. METHODS: We obtained obesity-related datasets from the Gene Expression Omnibus (GEO) database. GSE135830 comprises gene expression data from the hypothalamus of mouse offspring in a maternal obesity model induced by a high-fat diet model (maternal high-fat diet (mHFD) group and maternal chow (mChow) group), while GSE127056 consists of hypothalamus microarray data from young adult mice with obesity (high-fat diet (HFD) and Chow groups). We identified differentially expressed genes (DEGs) and module genes using Limma and weighted gene co-expression network analysis (WGCNA), conducted functional enrichment analysis, and employed a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to pinpoint candidate hub genes for diagnosing obesity-associated risk in offspring of maternal obesity. We constructed a nomogram receiver operating characteristic (ROC) curve to evaluate the diagnostic value. Additionally, we analyzed immune cell infiltration to investigate immune cell dysregulation in maternal obesity. Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro. RESULTS: The GSE135830 dataset revealed 2868 DEGs between the mHFD offspring and the mChow group and 2627 WGCNA module genes related to maternal obesity. The overlap of DEGs and module genes in the offspring with maternal obesity in GSE135830 primarily enriched in neurodevelopment and immune regulation. In the GSE127056 dataset, 133 DEGs were identified in the hypothalamus of HFD-induced adult obese individuals. A total of 13 genes intersected between the GSE127056 adult obesity DEGs and the GSE135830 maternal obesity module genes that were primarily enriched in neurodevelopment and the immune response. Following machine learning, two candidate hub genes were chosen for nomogram construction. Diagnostic value evaluation by ROC analysis determined Sytl4 and Kncn2 as hub genes for maternal obesity in the offspring. A gene regulatory network with transcription factor-miRNA interactions was established. Dysregulated immune cells were observed in the hypothalamus of offspring with maternal obesity. Expression of Sytl4 and Kncn2 was validated in a mouse model of hypothalamic inflammation and a palmitic acid-stimulated microglial inflammation model. CONCLUSION: Two candidate hub genes (Sytl4 and Kcnc2) were identified and a nomogram was developed to predict obesity risk in offspring with maternal obesity. These findings offer potential diagnostic candidate genes for identifying obesity-associated risks in the offspring of obese mothers.


Assuntos
MicroRNAs , Obesidade Materna , Humanos , Gravidez , Adulto Jovem , Feminino , Animais , Camundongos , Obesidade/genética , Biologia Computacional , Inflamação
14.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167057, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38331111

RESUMO

During inguinal adipose tissue (iWAT) ontogenesis, beige adipocytes spontaneously appear between postnatal 10 (P10) and P20 and their ablation impairs iWAT browning capacity in adulthood. Since maternal obesity has deleterious effects on offspring iWAT function, we aimed to investigate its effect in spontaneous iWAT browning in offspring. Female C57BL/6 J mice were fed a control or obesogenic diet six weeks before mating. Male and female offspring were euthanized at P10 and P20 or weaned at P21 and fed chow diet until P60. At P50, mice were treated with saline or CL316,243, a ß3-adrenoceptor agonist, for ten days. Maternal obesity induced insulin resistance at P60, and CL316,243 treatment effectively restored insulin sensitivity in male but not female offspring. This discrepancy occurred due to female offspring severe browning impairment. During development, the spontaneous iWAT browning and sympathetic nerve branching at P20 were severely impaired in female obese dam's offspring but occurred normally in males. Additionally, maternal obesity increased miR-22 expression in the iWAT of male and female offspring during development. ERα, a target and regulator of miR-22, was concomitantly upregulated in the male's iWAT. Next, we evaluated miR-22 knockout (KO) offspring at P10 and P20. The miR-22 deficiency does not affect spontaneous iWAT browning in females and, surprisingly, anticipates iWAT browning in males. In conclusion, maternal obesity impairs functional iWAT development in the offspring in a sex-specific way that seems to be driven by miR-22 levels and ERα signaling. This impacts adult browning capacity and glucose homeostasis, especially in female offspring.


Assuntos
Adipócitos Bege , MicroRNAs , Obesidade Materna , Animais , Feminino , Masculino , Camundongos , Gravidez , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Obesidade/genética , Obesidade/metabolismo , Obesidade Materna/metabolismo
15.
Int J Mol Sci ; 25(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38396912

RESUMO

Obese individuals often suffer from metabolic health disorders and reduced oocyte quality. Preconception diet interventions in obese outbred mice restore metabolic health and oocyte quality and mitochondrial ultrastructure. Also, studies in inbred mice have shown that maternal obesity induces metabolic alterations and reduces oocyte quality in offspring (F1). Until now, the effect of maternal high-fat diet on F1 metabolic health and oocyte quality and the potential beneficial effects of preconception dietary interventions have not been studied together in outbred mice. Therefore, we fed female mice a high-fat/high-sugar (HF/HS) diet for 7 weeks and switched them to a control (CONT) or caloric-restriction (CR) diet or maintained them on the HF/HS diet for 4 weeks before mating, resulting in three treatment groups: diet normalization (DN), CR, and HF/HS. In the fourth group, mice were fed CONT diet for 11 weeks (CONT). HF/HS mice were fed an HF/HS diet from conception until weaning, while all other groups were then fed a CONT diet. After weaning, offspring were kept on chow diet and sacrificed at 11 weeks. We observed significantly elevated serum insulin concentrations in female HF/HS offspring and a slightly increased percentage of mitochondrial ultrastructural abnormalities, mitochondrial size, and mitochondrial mean gray intensity in HF/HS F1 oocytes. Also, global DNA methylation was increased and cellular stress-related proteins were downregulated in HF/HS F1 oocytes. Mostly, these alterations were prevented in the DN group, while, in CR, this was only the case for a few parameters. In conclusion, this research has demonstrated for the first time that a maternal high-fat diet in outbred mice has a moderate impact on female F1 metabolic health and oocyte quality and that preconception DN is a better strategy to alleviate this compared to CR.


Assuntos
Obesidade Materna , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Gravidez , Camundongos , Animais , Obesidade/metabolismo , Dieta Hiperlipídica/efeitos adversos , Obesidade Materna/metabolismo , Mitocôndrias/metabolismo , Açúcares/metabolismo , Oócitos/metabolismo , Camundongos Endogâmicos C57BL , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal/metabolismo
16.
Medicina (Kaunas) ; 60(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38399481

RESUMO

Background and Objectives: Low-birth-weight (LBW) neonates are at increased risk of morbidity and mortality which are inversely proportional to birth weight, while macrosomic babies are at risk of birth injuries and other related complications. Many maternal risk factors were associated with the extremes of birthweight. The objectives of this study are to investigate maternal risk factors for low and high birthweight and to report on the neonatal complications associated with abnormal birth weights. Materials and Methods: We conducted a retrospective analysis of medical records of deliveries ≥ 23 weeks. We classified the included participants according to birth weight into normal birth weight (NBW), LBW, very LBW (VLBW), and macrosomia. The following maternal risk factors were included, mother's age, parity, maternal body mass index (BMI), maternal diabetes, and hypertension. The neonatal outcomes were APGAR scores < 7, admission to neonatal intensive care unit (NICU), respiratory distress (RD), and hyperbilirubinemia. Data were analyzed using SAS Studio, multivariable logistic regression analyses were used to investigate the independent effect of maternal risk factors on birthweight categories and results were reported as an adjusted odds ratio (aOR) and 95% Confidence Interval (CI). Results: A total of 1855 were included in the study. There were 1638 neonates (88.3%) with NBW, 153 (8.2%) with LBW, 27 (1.5%) with VLBW, and 37 (2.0%) with macrosomia. LBW was associated with maternal hypertension (aOR = 3.5, 95% CI = 1.62-7.63), while increasing gestational age was less likely associated with LBW (aOR = 0.51, 95% CI = 0.46-0.57). Macrosomia was associated with maternal diabetes (aOR = 3.75, 95% CI = 1.67-8.41), in addition to maternal obesity (aOR = 3.18, 95% CI = 1.24-8.14). The odds of VLBW were reduced significantly with increasing gestational age (aOR = 0.41, 95% CI = 0.32-0.53). In total, 81.5% of VLBW neonates were admitted to the NICU, compared to 47.7% of LBW and 21.6% of those with macrosomia. RD was diagnosed in 59.3% of VLBW neonates, in 23% of LBW, in 2.7% of macrosomic and in 3% of normal-weight neonates. Hyperbilirubinemia was reported in 37.04%, 34.21%, 22.26%, and 18.92% of VLBW, LBW, NBW, and macrosomic newborns, respectively. Conclusions: Most neonates in this study had normal birthweights. Maternal hypertension and lower gestational age were associated with increased risk of LBW. Additionally, maternal obesity and diabetes increased the risk of macrosomia. Neonatal complications were predominantly concentrated in the LBW and VLBW, with a rising gradient as birthweight decreased. The main complications included respiratory distress and NICU admissions.


Assuntos
Diabetes Gestacional , Hipertensão , Obesidade Materna , Pré-Eclâmpsia , Síndrome do Desconforto Respiratório , Recém-Nascido , Gravidez , Feminino , Humanos , Peso ao Nascer , Resultado da Gravidez/epidemiologia , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/etiologia , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Diabetes Gestacional/epidemiologia , Recém-Nascido de muito Baixo Peso , Fatores de Risco , Hiperbilirrubinemia
17.
J Agric Food Chem ; 72(9): 4703-4725, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38349207

RESUMO

Maternal obesity increases the risk of obesity and metabolic disorders (MDs) in offspring, which can be mediated by the gut microbiota. Phlorizin (PHZ) can improve gut dysbiosis and positively affect host health; however, its transgenerational metabolic benefits remain largely unclear. This study aimed to investigate the potential of maternal PHZ intake in attenuating the adverse impacts of a maternal high-fat diet on obesity-related MDs in dams and offspring. The results showed that maternal PHZ reduced HFD-induced body weight gain and fat accumulation and improved glucose intolerance and abnormal lipid profiles in both dams and offspring. PHZ improved gut dysbiosis by promoting expansion of SCFA-producing bacteria, Akkermansia and Blautia, while inhibiting LPS-producing and pro-inflammatory bacteria, resulting in significantly increased fecal SCFAs, especially butyric acid, and reduced serum lipopolysaccharide levels and intestinal inflammation. PHZ also promoted intestinal GLP-1/2 secretion and intestinal development and enhanced gut barrier function by activating G protein-coupled receptor 43 (GPR43) in the offspring. Antibiotic-treated mice receiving FMT from PHZ-regulated offspring could attenuate MDs induced by receiving FMT from HFD offspring through the gut microbiota to activate the GPR43 pathway. It can be regarded as a promising functional food ingredient for preventing intergenerational transmission of MDs and breaking the obesity cycle.


Assuntos
Microbioma Gastrointestinal , Doenças Metabólicas , Obesidade Materna , Humanos , Animais , Camundongos , Feminino , Gravidez , Florizina , Disbiose , Obesidade/metabolismo , Dieta Hiperlipídica/efeitos adversos , Doenças Metabólicas/etiologia , Doenças Metabólicas/prevenção & controle , Lipopolissacarídeos , Camundongos Endogâmicos C57BL
18.
Eur Thyroid J ; 13(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38417259

RESUMO

Objective: Obesity is associated with increased thyroid-stimulating hormone (TSH) in non-pregnant subjects, but this phenomenon has not been fully characterized during pregnancy. Our aim was to evaluate the impact of BMI on first-trimester TSH in a wide cohort of pregnant women with negative anti-thyroperoxidase antibodies (AbTPO) and its implications on uterine artery pulsatility index (UtA-PI), a marker of early placentation. Methods: The study included 2268 AbTPO-negative pregnant women at their first antenatal visit. Anamnestic data, BMI, TSH, anti-nuclear antibody (ANA) and extractable nuclear antigen (ENA) positivity and mean UtA-PI were collected. Results: A total of 1693 women had normal weight, 435 were overweight and 140 were obese. Maternal age, ANA/ENA positivity, history of autoimmune diseases and familiar history of thyroid diseases were similar in the three groups. TSH was significantly higher in obese women (1.8 (IQR: 1.4-2.4) mU/L) when compared to normal weight (1.6 (IQR: 1.2-2.2) mU/L) and overweight (median: 1.6 (IQR: 1.2-2.2) mU/L) ones (P < 0.001). BMI was significantly related with the risk of having a TSH level ≥4 mU/L at logistic regression, independently from non-thyroid autoimmunity, smoking or familiar predisposition for thyroid diseases (OR: 1.125, 95% CI: 1.080-1.172, P < 0.001). A restricted cubic splines regression showed a non-linear relationship between BMI and TSH. Women with a TSH ≥4 mU/L had a higher UtA-PI, independently from BMI. Conclusion: Overweight/obesity is significantly related with TSH serum levels in AbTPO-negative pregnant women, independently from the other risk factors for hypothyroidism during pregnancy. The increase of TSH levels could be clinically relevant, as suggested by its association with abnormal UtA-PI, a surrogate marker of abnormal placentation.


Assuntos
Obesidade Materna , Doenças da Glândula Tireoide , Tireotropina , Feminino , Humanos , Gravidez , Doenças Autoimunes , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Primeiro Trimestre da Gravidez
19.
Nutrients ; 16(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38337626

RESUMO

Maternal obesity and/or high-fat diet (HF) consumption can disrupt appetite regulation in their offspring, contributing to transgenerational obesity and metabolic diseases. As fatty acids (FAs) play a role in appetite regulation, we investigated the maternal and fetal levels of FAs as potential contributors to programmed hyperphagia observed in the offspring of obese dams. Female mice were fed either a control diet (CT) or HF prior to mating, and fetal and maternal blood and tissues were collected at 19 days of gestation. Elevated levels of linoleic acid were observed in the serum of HF dams as well as in the serum of their fetuses. An increased concentration of eicosadienoic acid was also detected in the hypothalamus of female HF-O fetuses. HF-O male fetuses showed increased hypothalamic neuropeptide Y (Npy) gene expression, while HF-O female fetuses showed decreased hypothalamic pro-opiomelanocortin (POMC) protein content. Both male and female fetuses exhibited reduced hypothalamic neurogenin 3 (NGN-3) gene expression. In vitro experiments confirmed that LA contributed to the decreased gene expression of Pomc and Ngn-3 in neuronal cells. During lactation, HF female offspring consumed more milk and had a higher body weight compared to CT. In summary, this study demonstrated that exposure to HF prior to and during gestation alters the FA composition in maternal serum and fetal serum and hypothalamus, particularly increasing n-6, which may play a role in the switch from POMC to NPY neurons, leading to increased weight gain in the offspring during lactation.


Assuntos
Neuropeptídeos , Obesidade Materna , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Animais , Masculino , Gravidez , Camundongos , Dieta Hiperlipídica/efeitos adversos , Obesidade Materna/metabolismo , Ácidos Graxos/metabolismo , Pró-Opiomelanocortina/metabolismo , Obesidade/metabolismo , Aumento de Peso , Neuropeptídeos/metabolismo , Hipotálamo/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal/metabolismo
20.
J Neuroinflammation ; 21(1): 39, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308309

RESUMO

BACKGROUND: Children born to obese mothers are at increased risk of developing mood disorders and cognitive impairment. Experimental studies have reported structural changes in the brain such as the gliovascular unit as well as activation of neuroinflammatory cells as a part of neuroinflammation processing in aged offspring of obese mothers. However, the molecular mechanisms linking maternal obesity to poor neurodevelopmental outcomes are not well established. The ephrin system plays a major role in a variety of cellular processes including cell-cell interaction, synaptic plasticity, and long-term potentiation. Therefore, in this study we determined the impact of maternal obesity in pregnancy on cortical, hippocampal development, vasculature and ephrin-A3/EphA4-signaling, in the adult offspring in mice. METHODS: Maternal obesity was induced in mice by a high fat/high sugar Western type of diet (HF/HS). We collected brain tissue (prefrontal cortex and hippocampus) from 6-month-old offspring of obese and lean (control) dams. Hippocampal volume, cortical thickness, myelination of white matter, density of astrocytes and microglia in relation to their activity were analyzed using 3-D stereological quantification. mRNA expression of ephrin-A3, EphA4 and synaptic markers were measured by qPCR in the brain tissue. Moreover, expression of gap junction protein connexin-43, lipocalin-2, and vascular CD31/Aquaporin 4 were determined in the hippocampus by immunohistochemistry. RESULTS: Volume of hippocampus and cortical thickness were significantly smaller, and myelination impaired, while mRNA levels of hippocampal EphA4 and post-synaptic density (PSD) 95 were significantly lower in the hippocampus in the offspring of obese dams as compared to offspring of controls. Further analysis of the hippocampal gliovascular unit indicated higher coverage of capillaries by astrocytic end-feet, expression of connexin-43 and lipocalin-2 in endothelial cells in the offspring of obese dams. In addition, offspring of obese dams demonstrated activation of microglia together with higher density of cells, while astrocyte cell density was lower. CONCLUSION: Maternal obesity affects brain size, impairs myelination, disrupts the hippocampal gliovascular unit and decreases the mRNA expression of EphA4 and PSD-95 in the hippocampus of adult offspring. These results indicate that the vasculature-glia cross-talk may be an important mediator of altered synaptic plasticity, which could be a link between maternal obesity and neurodevelopmental/neuropsychiatric disorders in the offspring.


Assuntos
Obesidade Materna , Efeitos Tardios da Exposição Pré-Natal , Humanos , Criança , Camundongos , Animais , Feminino , Gravidez , Idoso , Lactente , Obesidade Materna/metabolismo , Lipocalina-2/metabolismo , Efrinas/metabolismo , Efrina-A3/genética , Efrina-A3/metabolismo , Filhos Adultos , Células Endoteliais/metabolismo , Obesidade/metabolismo , Hipocampo/metabolismo , RNA Mensageiro/metabolismo , Conexinas/genética , Conexinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismo
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