scholarly journals Maternal diet-induced obesity during pregnancy alters lipid supply to mouse E18.5 fetuses and changes the cardiac tissue lipidome in a sex-dependent manner

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Lucas C Pantaleao ◽  
Isabella Inzani ◽  
Samuel Furse ◽  
Elena Loche ◽  
Antonia Hufnagel ◽  
...  
Keyword(s):  
Cardiovascular Health ◽  
Cardiac Tissue ◽  
Maternal Obesity ◽  
Fetal Heart ◽  
Maternal Diet ◽  
Late Gestation ◽  
Sexually Dimorphic ◽  
Dependent Manner ◽  
Early Expression ◽  
Pregnant Mice

Maternal obesity during pregnancy has immediate and long-term detrimental effects on the offspring heart. In this study, we characterized the cardiac and circulatory lipid profiles in late gestation E18.5 fetuses of diet-induced obese pregnant mice and established the changes in lipid abundance and fetal cardiac transcriptomics. We used untargeted and targeted lipidomics and transcriptomics to define changes in the serum and cardiac lipid composition and fatty acid metabolism in male and female fetuses. From these analyses we observed: (1) maternal obesity affects the maternal and fetal serum lipidome distinctly; (2) female fetal heart lipidomes are more sensitive to maternal obesity than males; (3) changes in lipid supply might contribute to early expression of lipolytic genes in mouse hearts exposed to maternal obesity. These results highlight the existence of sexually dimorphic responses of the fetal heart to the same in utero obesogenic environment and identify lipids species that might mediate programming of cardiovascular health.

scholarly journals Maternal diet-induced obesity during pregnancy alters lipid supply to fetuses and changes the cardiac tissue lipidome in a sex-dependent manner

2021 ◽  
Author(s):  
Lucas C. Pantaleão ◽  
Isabella Inzani ◽  
Samuel Furse ◽  
Elena Loche ◽  
Antonia Hufnagel ◽  
...  
Keyword(s):  
Cardiovascular Health ◽  
Cardiac Tissue ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Sexually Dimorphic ◽  
Dependent Manner ◽  
Diet Induced Obesity ◽  
Early Expression ◽  
Pregnant Mice

ABSTRACTMaternal obesity during pregnancy has immediate and long-term detrimental effects on the offspring heart. In this study, we characterized the cardiac and circulatory lipid profiles in fetuses of diet-induced obese pregnant mice and established the changes in lipid abundance and fetal cardiac transcriptomics. We used untargeted and targeted lipidomics and transcriptomics to define changes in the serum and cardiac lipid composition and fatty acid metabolism in male and female fetuses. From these analyses we observed: (1) maternal obesity affects the maternal and fetal serum lipidome distinctly; (2) female heart lipidomes are more sensitive to maternal obesity than male fetuses; (3) changes in lipid supply might contribute to early expression of lipolytic genes in mouse hearts exposed to maternal obesity. These results highlight the existence of sexually dimorphic responses of the fetal heart to the same in utero obesogenic environment and identify lipids species that might mediate programming of cardiovascular health.

scholarly journals Diet reduction to requirements in obese/overfed ewes from early gestation prevents glucose/insulin dysregulation and returns fetal adiposity and organ development to control levels

2013 ◽  
Vol 305 (7) ◽  
pp. E868-E878 ◽  
Author(s):  
Nuermaimaiti Tuersunjiang ◽  
John F. Odhiambo ◽  
Nathan M. Long ◽  
Desiree R. Shasa ◽  
Peter W. Nathanielsz ◽  
...  
Keyword(s):  
Maternal Obesity ◽  
Maternal Diet ◽  
Control Diet ◽  
Plasma Concentrations ◽  
National Research Council ◽  
Late Gestation ◽  
Early Gestation ◽  
Fetal Organ ◽  
Insulin Dysregulation ◽  
Fetal Size

Obesity at conception and excess gestational weight gain pose significant risks for adverse health consequences in human offspring. This study evaluated the effects of reducing dietary intake of obese/overfed ewes beginning in early gestation on fetal development. Sixty days prior to conception, ewes were assigned to a control diet [CON: 100% of National Research Council (NRC) recommendations], a diet inducing maternal obesity (MO: 150% of NRC recommendations), or a maternal obesity intervention diet (MOI: 150% of NRC recommendations to day 28 of gestation, then 100% NRC) until necropsy at midgestation ( day 75) or late ( day 135) gestation. Fetal size and weight, as well as fetal organ weights, were greater ( P < 0.05) at midgestation in MO ewes than those of CON and MOI ewes. By late gestation, whereas fetal size and weight did not differ among dietary groups, cardiac ventricular weights and wall thicknesses as well as liver and perirenal fat weights remained elevated in fetuses from MO ewes compared with those from CON and MOI ewes. MO ewes and fetuses exhibited elevated ( P < 0.05) plasma concentrations of triglycerides, cholesterol, insulin, glucose, and cortisol at midgestation compared with CON and MOI ewes and fetuses. In late gestation, whereas plasma triglycerides and cholesterol, insulin, and cortisol remained elevated in MO vs. CON and MOI ewes and fetuses, glucose concentrations were elevated in both MO and MOI fetuses compared with CON fetuses, which was associated with elevated placental GLUT3 expression in both groups. These data are consistent with the concept that reducing maternal diet of obese/overfed ewes to requirements from early gestation can prevent subsequent alterations in fetal growth, adiposity, and glucose/insulin dynamics.

scholarly journals Maternal obesity programs white and brown adipose tissue transcriptome and lipidome in offspring in a sex-dependent manner

2021 ◽  
Author(s):  
Christina Savva ◽  
Luisa A. Helguero ◽  
Marcela González-Granillo ◽  
Tânia Melo ◽  
Daniela Couto ◽  
...  
Keyword(s):  
Maternal Obesity ◽  
Maternal Diet ◽  
Overweight And Obesity ◽  
Male Offspring ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Metabolic Complications ◽  
Adipose Tissues ◽  
The Metabolic Syndrome ◽  
Brown Adipose

SUMMARYThe prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational epigenetic regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring. In this work, we investigated the sex-dependent programming of maternal obesity in visceral, subcutaneous and brown adipose tissues of offspring using magnetic resonance imaging and spectroscopy and a lipidomic approach combined with a Smart-Seq2 differential sequencing analysis. We show that the triglyceride profile varies between adipose depots, sexes and maternal diet. Our results demonstrate for the first time that a sex-dependent gene programming exists in visceral, subcutaneous and brown adipose tissues. Maternal obesity differentially programs gene expression in adipose depots of female and male offspring, which may contribute to the sex-dependent metabolic complications later in life.Graphical abstract

scholarly journals Mechanisms Underlying the Cognitive and Behavioural Effects of Maternal Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 240
Author(s):  
Kyoko Hasebe ◽  
Michael D. Kendig ◽  
Margaret J. Morris
Keyword(s):  
Animal Models ◽  
Adverse Effects ◽  
Gut Microbiome ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Affective State ◽  
Brain Regions ◽  
Brain Network ◽  
Physical And Mental Health ◽  
Obesogenic Diet

The widespread consumption of ‘western’-style diets along with sedentary lifestyles has led to a global epidemic of obesity. Epidemiological, clinical and preclinical evidence suggests that maternal obesity, overnutrition and unhealthy dietary patterns programs have lasting adverse effects on the physical and mental health of offspring. We review currently available preclinical and clinical evidence and summarise possible underlying neurobiological mechanisms by which maternal overnutrition may perturb offspring cognitive function, affective state and psychosocial behaviour, with a focus on (1) neuroinflammation; (2) disrupted neuronal circuities and connectivity; and (3) dysregulated brain hormones. We briefly summarise research implicating the gut microbiota in maternal obesity-induced changes to offspring behaviour. In animal models, maternal obesogenic diet consumption disrupts CNS homeostasis in offspring, which is critical for healthy neurodevelopment, by altering hypothalamic and hippocampal development and recruitment of glial cells, which subsequently dysregulates dopaminergic and serotonergic systems. The adverse effects of maternal obesogenic diets are also conferred through changes to hormones including leptin, insulin and oxytocin which interact with these brain regions and neuronal circuits. Furthermore, accumulating evidence suggests that the gut microbiome may directly and indirectly contribute to these maternal diet effects in both human and animal studies. As the specific pathways shaping abnormal behaviour in offspring in the context of maternal obesogenic diet exposure remain unknown, further investigations are needed to address this knowledge gap. Use of animal models permits investigation of changes in neuroinflammation, neurotransmitter activity and hormones across global brain network and sex differences, which could be directly and indirectly modulated by the gut microbiome.

Nitric Oxide levels and the uNK cell aspects as clinical predictors in induction–inflammation model during pregnancy and neurological problem 

2020 ◽  
Vol 9 (2) ◽  
pp. 50-57
Author(s):  
Luiza Lucchesi de Oliveira ◽  
Eliana Mara Oliveira Lippe
Keyword(s):  
Nitric Oxide ◽  
Tissue Homogenate ◽  
Dependent Manner ◽  
Clinical Predictors ◽  
Paraffin Embedding ◽  
Unk Cells ◽  
Neurological Problem ◽  
Tissue Homogenates ◽  
Pregnant Mice ◽  
Neurological Injuries

The successful of pregnancy in humans and rodents occur between the interaction maternal and fetal interface, specially involving the participation of uNK cells. This interaction involved neo angiogenesis, placentation and presence of mediators like nitric oxide. During the pregnancy the administration of LPS in the dams can results in necrosis, preterm birth, IUGR, miscarriage or neurological problem. Once the uNK cells are activated, they can produce vasodilators, like NO. So, the main purpose of this study was to evaluate if LPS cause alteration in the uNK cells in pregnant mice and if the same behaviour can be detected by NO in the blood. Also we evaluated the effect of LPS to cause neurological injuries. To do that we used pregnant mice on gd 10th and those was treated with LPS for different times. Uterine samples were collected at 0.5,1,2 and 6hr after LPS treated and processed for paraffin embedding and tissue homogenate. The samples designated for paraffin embedding was performed the Dolichos biflorus (DBA) lectin cytochemistry and anti-iNOS immunocytochemistry. The samples designated to tissue homogenates were processed for SDS-PAGE and Western-blot using anti-iNOS and evaluate of NO concentration. We found after 2h LPS exposure the mice showed fever and low capacity to explore different environment. At the same time, we found increase in the nitrate/nitrito ratio in a dose dependent manner in the uterus after 2h LPS exposure. The uNK cells were the main cell that was staining for iNOS isoform. Also, we found that wall:lumen ratio is very higher in treated mice than the control mice. The LPS is able to induce the activation of uNK cells and this action is involved by releasing NO in higher amount. So, it is possible to consider the uNK cells as a potential element of maternal-fetal interface in the production of NO and knowing that the isoforms is reduced in these cells, a model of NOS inhibition could be considered to elucidate the participation of uNK cells as a possible cause of effectors loss or interruption of pregnancy.

Pygo1 regulates pathological cardiac hypertrophy via a β-catenin-dependent mechanism

2021 ◽  
Author(s):  
Li Lin ◽  
Wei Xu ◽  
Yongqing Li ◽  
Ping Zhu ◽  
Wuzhou Yuan ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Tissue ◽  
Heart Weight ◽  
Dependent Manner ◽  
Tissue Specific ◽  
Cardiac Tissues ◽  
Pathological Cardiac Hypertrophy ◽  
Interaction Factor ◽  
Myocardial Remodelling

Wnt/β-catenin signalling plays a key role in pathological cardiac remodelling in adults. The identification of a tissue-specific Wnt/β-catenin interaction factor may realise a tissue-specific clinical targeting strategy. Drosophila Pygo codes for the core interaction factor of Wnt/β-catenin. Two Pygo homologs, Pygo1 and Pygo2, have been identified in mammals. Different from the ubiquitous expression profile of Pygo2, Pygo1is enriched in cardiac tissue. However, the role of Pygo1 in mammalian cardiac disease remains unelucidated. Here, we found that Pygo1 was upregulated in human cardiac tissues with pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy accompanied by declined cardiac function, increased heart weight/body weight and heart weight/tibial length ratios and increased cell size. The canonical β-catenin/T-cell transcription factor 4 complex was abundant in Pygo1-overexpressingtransgenic(Pygo1-TG) cardiac tissue,and the downstream genes of Wnt signaling, i.e., Axin2, Ephb3, and C-myc, were upregulated. A tail vein injection of β-catenin inhibitor effectively rescued the phenotype of cardiac failure and pathological myocardial remodelling in Pygo1-TG mice. Furthermore, in vivo downregulated pygo1 during cardiac hypertrophic condition antagonized agonist-induced cardiac hypertrophy. Therefore, our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/β-catenin-dependent manner, which may provide new clues for a tissue-specific clinical treatment targeting this pathway.

scholarly journals Perfluorooctanoic Acid Exposure in Early Pregnancy Induces Oxidative Stress in The Uterus and Liver in Mice

2021 ◽  
Author(s):  
Yan Zhang ◽  
Linchao Zhang ◽  
JiaLu Bao ◽  
LianTao Liu ◽  
Xiaodan Wang
Keyword(s):  
Early Pregnancy ◽  
Caspase 3 ◽  
Liver Toxicity ◽  
Liver Weight ◽  
Perfluorooctanoic Acid ◽  
Control Group ◽  
Dependent Manner ◽  
Subsequent Increase ◽  
Decidual Cells ◽  
Pregnant Mice

Abstract To investigate the mechanism perfluorooctanoic acid (PFOA)’s toxicity on the uterus and liver of the mice during early pregnancy, pregnant mice were given 0, 1, 5, 10, 20, 40 mg/kg PFOA daily by gavage from gestational day (GD) 1-7, and sacrificed on GD 9. Uterus and liver weight were recorded, liver and uterine indexes were calculated, histopathological changes of the liver and uterus were examined, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in liver were detected by spectrophotometric method. Expression of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells were detected by immunohistochemistry and the TUNEL method was used to detect apoptotic uterine cells. Results showed that liver weight increased, and the uterus index was significantly reduced at 40 mg/kg compared with the control group. With increasing doses of PFOA, levels of SOD and GSH-PX were significantly decreased, and MDA significantly increased in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused greater harm to the uterus and congestion and resorption may occur. Expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was down-regulated, which decreased the ratio of Bcl-2/Bax. It is therefore proposed that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may induce embryo loss or damage.

132 Early Establishment of the Human Gut Microbiome—a Tale of Moms, Their Diets, and Babes Guts

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 68-68
Author(s):  
Kjersti M Aagaard
Keyword(s):  
Gut Microbiome ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Dietary Exposure ◽  
Metabolic Phenotype ◽  
Strong Impact ◽  
High Fat ◽  
Lower Genital Tract ◽  
And Function ◽  
The Impact

Abstract Human microbial communities are characterized by their metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. We are only beginning to characterize the complex set of interactions which alters both community membership and function in early development. With respect to the potential source of microbiota at birth, it has been generally assumed that the majority of seeding microbes originate from the maternal lower genital tract, with microbiota ascending into the otherwise sterile intrauterine. However, we and subsequently others have recently demonstrated that (1) the vaginal and gut microbiome communities are distinctly structured in pregnancy, and (2) the intrauterine environment and the fetus is in fact not sterile, but rather harbors a low-abundance microbiome which varies by several measured exposures, and (3) the maternal diet during both gestation and lactation, and notably a high fat diet, has a particularly strong impact on the developing and early in life microbial community structure. We have taken two dynamic approaches to answering these questions in our studies. First, we use large and robust longitudinal cohorts of maternal-infant dyads collected across gestation and into infancy to gain deeper insight into both source and sink of the early developmental microbiome and its role on determining length of gestation. Second, we utilize our well established primate models of maternal high fat dietary exposure, both in the absence and presence of maternal obesity, to determine the impact of maternal diet on both the microbiome and the resultant offspring metabolic phenotype.

scholarly journals Obesity during pregnancy results in maternal intestinal inflammation, placental hypoxia, and alters fetal glucose metabolism at mid-gestation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jessica G. Wallace ◽  
Christian J. Bellissimo ◽  
Erica Yeo ◽  
Yu Fei Xia ◽  
Jim J. Petrik ◽  
...  
Keyword(s):  
Structural Changes ◽  
Maternal Obesity ◽  
Intestinal Inflammation ◽  
Maternal Diet ◽  
Cell Number ◽  
Amino Acid Transporters ◽  
Metabolic Dysfunction ◽  
Transcript Levels ◽  
Increased Risk ◽  
Placental Inflammation

AbstractWe investigated whether diet-induced changes in the maternal intestinal microbiota were associated with changes in bacterial metabolites and their receptors, intestinal inflammation, and placental inflammation at mid-gestation (E14.5) in female mice fed a control (17% kcal fat, n = 7) or a high-fat diet (HFD 60% kcal fat, n = 9; ad libitum) before and during pregnancy. Maternal diet-induced obesity (mDIO) resulted in a reduction in maternal fecal short-chain fatty acid producing Lachnospiraceae, lower cecal butyrate, intestinal antimicrobial peptide levels, and intestinal SCFA receptor Ffar3, Ffar2 and Hcar2 transcript levels. mDIO increased maternal intestinal pro-inflammatory NFκB activity, colonic CD3+ T cell number, and placental inflammation. Maternal obesity was associated with placental hypoxia, increased angiogenesis, and increased transcript levels of glucose and amino acid transporters. Maternal and fetal markers of gluconeogenic capacity were decreased in pregnancies complicated by obesity. We show that mDIO impairs bacterial metabolite signaling pathways in the mother at mid-gestation, which was associated with significant structural changes in placental blood vessels, likely as a result of placental hypoxia. It is likely that maternal intestinal changes contribute to adverse maternal and placental adaptations that, via alterations in fetal hepatic glucose handling, may impart increased risk of metabolic dysfunction in offspring.

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