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Maternal adipose tissue DNA methylation and gene expression associated with excessive gestational weight gain

ABSTRACT: Omental adipose tissue was obtained from 24 women aged 25-40 years with a healthy singleton pregnancy and a pre-pregnancy BMI of 18.5-26 kg/m2. Genomic DNA was extracted for promoter DNA methylation analysis of candidate genes LEP, TNF, NPY, POMC and SOCS3 using bisulfite amplicon sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239408 | GEO | 2024/07/26

REPOSITORIES: GEO

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Comparative transcriptomic analyses of developing melanocortin neurons reveal new regulators for the anorexigenic neuron identity

Project description:Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive.We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in E15.5 mice embryos. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons.Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role of Prdm12 in vivo, we developed and characterized a floxed Prdm12 allele. Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deletion of Prdm12 in adult POMC neurons showed that it is no longer required for Pomc expression nor energy balance. Collectively, these findings establish a critical role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Finally, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the hypothalamus whose neurodevelopment remains poorly studied.

2020-03-12 | GSE146816 | GEO

Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline

Project description:The arcuate nucleus of the hypothalamus (ARH) is one key structure controlling energy homeostasis. While it has been shown that the biogenic amines dopamine and serotonin modulate food intake controlling NPY/AgRP and/or POMC neurons in the ARH, the neural substrates that mediate the effect of noradrenaline (NA) on energy homeostasis remain elusive. By electrophysiological recordings and cell type-specific transcriptomics we show that the main neuronal populations in the ARH, NPY/AgRP and POMC neurons express a combination of excitatory and inhibitory adrenergic receptors (ARs). Surprisingly, NA had a clear differential effect on these neurons. Activation of NPY/AgRP neurons is mediated by _1A - and _- ARs, while POMC neurons are inhibited via _2A ARs. Collectively, our data indicate an orexigenic influence of NA on the ARH circuitry that controls energy balance

2017-10-26 | GSE106188 | GEO

EphrinB1 Modulates Glutamatergic Inputs into POMC Neurons and Controls Glucose Homeostasis

Project description:We aim at identifying genes enriched in POMC neurons versus NPY neurons that were involved in glutamatergic synapse formation

2020-02-07 | GSE144887 | GEO

Dopamine-inhibited POMCDrd2+ neurons in the ARC acutely regulate feeding and body temperature

Project description:Dopamine acts on neurons in the arcuate nucleus of the hypothalamus (ARC) which control homeostatic feeding responses. Here we demonstrate a differential enrichment of Drd1 expression in food intake-promoting AgRP/NPY neurons and a large proportion of Drd2-expressing anorexigenic POMC neurons. This translates into a predominant activation of AgRP/NPY neurons upon dopamine stimulation and a larger proportion of dopamine-inhibited POMC neurons. Employing intersectional targeting of Drd2-expressing POMC neurons, we reveal, that dopamine-mediated POMC neuron inhibition is Drd2-dependent and that POMCDrd2+ neurons exhibit differential expression of neuropeptide signaling mediators, which manifests in enhanced somatostatin responsiveness of these neurons compared to the global POMC neuron population. Retrograde pseudorabies mapping reveals predominant synaptic input onto these cells from within the ARC as well as characterized dopaminergic cell groups within the hypothalamus and subthalamic areas. Finally, selective chemogenetic activation of POMCDrd2+ neurons uncovers their ability to acutely suppress feeding and to preserve body temperature. Collectively, the present study provides the molecular and functional characterization of POMCDrd2+ neurons and aids to our understanding of dopamine-dependent control of homeostatic energy regulatory neurocircuits.

2022-11-08 | GSE210311 | GEO

Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline

Project description:Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline

| PRJNA415839 | ENA

Early Leptin Intervention Reverses Perturbed Energy Balance Regulating Hypothalamic Neuropeptides in the Pre- and Postnatal Calorie Restricted Offspring

Project description:Pre- and postnatal calorie restriction is associated with postnatal growth restriction, reduced circulating leptin concentrations and perturbed energy balance. Hypothalamic regulation of energy balance demonstrates enhanced orexigenic (NPY, AgRP) and diminished anorexigenic (POMC, CART) neuropeptide expression (PN21) setting the stage for subsequent development of obesity. Leptin replenishment during the early postnatal period (PN2-PN8) led to reversing the hypothalamic orexigenic:anorexigenic neuropeptide ratio at PN21 by only reducing the orexigenic (NPY, AgRP) without affecting the anorexigenic (POMC, CART) neuropeptide expression. This hypothalamic effect was mediated via enhanced leptin receptor (ObRb) signaling that involved increased pSTAT3 but reduced PTP1B. This was further confirmed by an increase in body weight at PN21 in response to intracerebroventricular administration of antisense ObRb oligonucleotides (PN2-PN8). The change in the hypothalamic neuropeptide balance in response to leptin administration caused increased oxygen consumption, carbon dioxide production and physical activity which resulted in increased milk intake (PN14) with no change in body weight. This is in contrast to the reduction in milk intake with no effect on energy expenditure and physical activity observed in controls. We conclude that pre- and postnatal calorie restriction perturbs hypothalamic neuropeptide regulation of energy balance setting the stage for hyperphagia and reduced energy expenditure, hallmarks of obesity. Leptin in turn reverses this phenotype by increasing hypothalamic ObRb signaling (sensitivity) and affecting only the orexigenic arm of the neuropeptide balance.

2014-12-31 | GSE55384 | GEO

Effect of diet-induced obesity on uterine function in mice.

Project description:To gain insight into the mechanism(s) by which obesogenic diet caused decreased uterine contractility at term, we collected uterine tissue from mice fed either a control (CON) or an obesogenic (DIO) diet at day 18.5 of pregnancy and performed RNA sequencing.

2024-05-28 | GSE268397 | GEO

Salivary proteome signatures in the early and middle stages of human pregnancy with term birth outcome

Project description:This prospective study is to find changes in salivary protein expressions from first to early third trimester of pregnancy in normal term birth using SWATH-MS strategy. Saliva at three periods of gestation, 6-13 (V1), 18-21(V2), and 26-29 (V3) weeks from 20 singleton pregnant women were used in a discovery phase. Selected proteins from the discovery study were verified by targeted schedule-MRM (multiple reaction monitoring) experiments in a separate subset of subjects (N=14). Using in-house generated saliva-specific protein library, 65 proteins (q-value<0.1) changed as a function of gestational age.

2020-09-28 | PXD014800 | Pride

Project description:Singleton Filtering

| PRJNA392425 | ENA

Effects of maternal zinc deficiency on placental development and function in mice

Project description:Zinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to determine how zinc is important to placental morphogenesis. Global placental gene expression at gestational day 18.5 was analysed using microarray to determine the effects of zinc deficiency on placental function.

2018-02-13 | GSE97112 | GEO

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