Metabolism Disrupting Chemicals and Alteration of Neuroendocrine Circuits Controlling Food Intake and Energy Metabolism

Marraudino, Marilena; Bonaldo, Brigitta; Farinetti, Alice; Panzica, Giancarlo; Ponti, Giovanna

doi:10.3389/fendo.2018.00766

Cited by 39 publications

(30 citation statements)

References 122 publications

(138 reference statements)

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“…The sexual dimorphic response specific to ER action has been associated with the development of or protection from certain diseases (e.g., metabolic syndrome and autoimmune diseases) [33][34][35][36]. As such, animal studies have demonstrated that exogenous exposures that inappropriately alter ER signaling can increase the relative risk for these diseases [37][38][39]. To determine whether the genetic sex of a cell could influence the transcriptional response to the xenoestrogens, we repeated our analysis of differentially expressed genes in HepaRG cells, which were derived from the liver of a female patient [40].…”

Section: The Role Of Genetic Sex In Mediating the Cellular Response Tmentioning

confidence: 99%

Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals

2020

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Background: An individual's response to environmental exposures varies depending on their genotype, which has been termed the gene-environment interaction. The phenotype of cell exposed can also be a key determinant in the response to physiological cues, indicating that a cell-gene-environment interaction may exist. We investigated whether the cellular environment could alter the transcriptional response to environmental chemicals. Publicly available gene expression array data permitted a targeted comparison of the transcriptional response to a unique subclass of environmental chemicals that alter the activity of the estrogen receptor, xenoestrogens. Results: Thirty xenoestrogens were included in the analysis, for which 426 human gene expression studies were identified. Comparisons were made for studies that met the predefined criteria for exposure length, concentration, and experimental replicates. The cellular response to the phytoestrogen genistein resulted in remarkably unique transcriptional profiles in breast, liver, and uterine cell-types. Analysis of gene regulatory networks and molecular pathways revealed that the cellular context mediated the activation or repression of functions important to cellular organization and survival, including opposing effects by genistein in breast vs. liver and uterine cell-types. When controlling for cell-type, xenoestrogens regulate unique gene networks and biological functions, despite belonging to the same class of environmental chemicals. Interestingly, the genetic sex of the cell-type also strongly influenced the transcriptional response to xenoestrogens in the liver, with only 22% of the genes significantly regulated by genistein common between male and female cells. Conclusions: Our results demonstrate that the transcriptional response to environmental chemicals depends on a variety of factors, including the cellular context, the genetic sex of a cell, and the individual chemical. These findings highlight the importance of evaluating the impact of exposure across cell-types, as the effect is responsive to the cellular environment. These comparative genetic results support the concept of a cell-gene-environment interaction.

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Section: The Role Of Genetic Sex In Mediating the Cellular Response Tmentioning

confidence: 99%

Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals

2020

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“…Several studies carried out in both humans and animals have shown that EDCs restrain the androgen receptor pathway, augment, or block the estrogen pathway, and/or decrease androgen levels through the up-regulation of the aromatase enzyme. These hormonal modifications lead to an increased number and size of adipose cells, altered adipocytokine production, reduction of basal metabolic rate, and modification of appetite and satiety signaling (85). Although the available data derived from animal studies are more solid than those obtained from human epidemiological studies, a link between EDCs and an adverse metabolic profile is predicted.…”

Section: Synthesis Of Datamentioning

confidence: 99%

Molecular and Environmental Mechanisms Regulating Puberty Initiation: An Integrated Approach

Livadas

Chrousos

2019

Front. Endocrinol.

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The mechanisms underlying the initiation of puberty, one of the cornerstones of human evolution, have not been fully elucidated as yet. However, recently, an accumulating body of evidence has helped unravel several critical aspects of the process. It is clear that a change in the pattern of pituitary gonadotropin secretion serves as a hormonal trigger for puberty induction. This change is directly guided by the hypothalamic GnRH pulse generation, a phenomenon regulated by the Kisspeptin-Neurokinin-Dynorphin (KNDy) system also in the hypothalamus. This represents the kisspeptin molecule, which is crucial in augmenting GnRH secretion at puberty, whose secretion is fine-tuned by the opposing signals neurokinin B and dynorphin. Recently, the novel kisspeptin inhibitory signal MKRN3 was described, whose role in puberty initiation provided further insight into the mechanistic aspects of pubertal onset. Furthermore, the description of higher inhibitory and stimulatory signals acting upstream of the KNDy neurons suggested that the trigger point of puberty is located upstream of the KNDy system and the GnRH pulse generator. However, the mechanism of pubertal onset should not be considered as an isolated closed loop system. On the contrary, it is influenced by such factors as adipose tissue, gastrointestinal function, adrenal androgen production, energy sensing, and physical and psychosocial stress. Also, fetal and early life stressful events, as well as exposure to endocrine disruptors, may play important roles in pubertal initiation, the latter primarily through epigenetic modifications. Here we present the available data in the field and attempt to provide an integrated view of this unique and crucial phenomenon.

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“…The hypothalamus in the central nervous system plays an essential role in the modulation of appetite and energy expenditure. Compromised hypothalamus regulation is involved in the development of obesity (Carmo-Silva and Cavadas, 2017;Marraudino et al, 2019;Seong et al, 2019). However, the effect of sleep curtailment on the regulation of appetite in the hypothalamus and the mechanisms underlying this are not fully understood and need further exploration.…”

Section: Introductionmentioning

confidence: 99%

Chronic Timed Sleep Restriction Attenuates LepRb-Mediated Signaling Pathways and Circadian Clock Gene Expression in the Rat Hypothalamus

et al. 2020

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The sleep duration of adolescents has continued to decline over the past 20 years. Sleep insufficiency is one of the most important risk factors for obesity, but the mechanisms underlying the association are unclear. Therefore, the hypothalamic-regulated mechanisms of appetite and the circadian clock gene expression were examined in sleep-restricted rats. Rats aged 7 weeks were randomly divided into two groups: the control group and sleep restriction group (7 rats/group) rats were sleep-restricted for 4 weeks. Body weight gain and amount of food/water consumption were quantified. The expression of genes or proteins which regulated appetite and energy metabolism via leptin receptor signaling and the circadian clock in the hypothalamus were assessed. Chronic sleep restriction induced increased food intake and weight gain in adolescent and young adult rats from the second week of initiation of sleep restriction. Phosphorylation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was decreased, although levels of circulating leptin or leptin receptor expression were unaltered. Furthermore, insulin receptor substrate (IRS)/phosphoinositide 3-kinase (PI3K)/AKT/mTOR and forkhead box O1 (FoxO1) signaling pathways were also compromised. Moreover, core circadian clock genes were also decreased in the sleep restriction group compared with the control. Chronic timed sleep restriction induced hyperphagic behaviors, attenuated leptin receptor-mediated signaling pathways, and depleted the expression of circadian clock gene in the hypothalamus of adolescent and young adult rats.

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Metabolism Disrupting Chemicals and Alteration of Neuroendocrine Circuits Controlling Food Intake and Energy Metabolism

Cited by 39 publications

References 122 publications

Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals

Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals

Molecular and Environmental Mechanisms Regulating Puberty Initiation: An Integrated Approach

Chronic Timed Sleep Restriction Attenuates LepRb-Mediated Signaling Pathways and Circadian Clock Gene Expression in the Rat Hypothalamus

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