Placental miR-340 mediates vulnerability to activity based anorexia in mice
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ABSTRACT:
PROVIDER: PRJNA434093 | ENA |
REPOSITORIES: ENA
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Project description:Anorexia nervosa (AN) is a devastating eating disorder characterized by self-starvation that mainly affects women. Its etiology is unknown, which impedes successful treatment options leading to a limited chance of full recovery. Here, we show that gestation is a vulnerable window that can influence the predisposition to AN. By screening placental microRNA expression of naive and prenatally stressed (PNS) fetuses and assessing vulnerability to activity-based anorexia (ABA) in early adulthood, we identify miR-340 as a sexually dimorphic regulator involved in prenatal programming of ABA. PNS caused gene-body hypermethylation of placental miR-340, which is associated with reduced miR-340 expression and increased protein levels of several target transcripts; Gr, Cry2 and H3F3b. MiR-340 is linked to the expression of several nutrient transporters both in mice and human placentas. Using placenta-specific lentiviral transgenes and embryo transfer, we demonstrate the key role miR-340 plays in the mechanism involved in early life programming of ABA.
2018-03-27 | GSE110597 | GEO
Project description:Anorexia nervosa (AN) is a devastating eating disorder characterized by self-starvation that mainly affects women. Its etiology is unknown, which impedes successful treatment options leading to a limited chance of full recovery. Here, we show that gestation is a vulnerable window that can influence the predisposition to AN. By screening placental microRNA expression of naive and prenatally stressed (PNS) fetuses and assessing vulnerability to activity-based anorexia (ABA), we identify miR-340 as a sexually dimorphic regulator involved in prenatal programming of ABA. PNS caused gene-body hypermethylation of placental miR-340, which is associated with reduced miR-340 expression and increased protein levels of several target transcripts, GR, Cry2 and H3F3b. MiR-340 is linked to the expression of several nutrient transporters both in mice and human placentas. Using placenta-specific lentiviral transgenes and embryo transfer, we demonstrate the key role miR-340 plays in the mechanism involved in early life programming of ABA.
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Project description:Anorexia and other side effects of chemotherapy significantly limit the clinical applications of these chemotherapeutic agents, with underlying mechanisms still unclear. A growing body of research reveals that elevated levels of circulating GDF15 after chemotherapy are essential in initiating anorexia and other side effects by activating GFRAL+ neurons in the brainstem. However, the full array of context-dependent transcriptional regulators controlling Gdf15 expression remains to be defined. This study reports that chemotherapy drugs acutely stimulate liver GDF15 production via selective activation of the hepatic stress sensor IRE1α, thereby controlling circulating GDF15 levels. Genetic ablation of hepatic IRE1α reduces circulating GDF15 and alleviates anorexia and body weight loss following chemotherapy drug treatments in tumor-bearing mice. Mechanistically, chemotherapy drugs activate hepatic IRE1α RNase activity to produce the active form of the transcription factor XBP1 to promotes the expression of Gdf15 gene in hepatocytes. Moreover, treatment with pharmacological IRE1α RNase inhibitor effectively suppresses liver Gdf15 expression and circulating GDF15 levels, resulting in improvements in chemotherapy-induced anorexia and body weight loss. Our results reveal a stress-responsive mechanism that mediates communication between the liver and brain. This mechanism can be targeted pharmacologically to alleviate anorexic side effects that accompany chemotherapy-induced body weight loss.
2024-04-22 | GSE235695 | GEO
Project description:Total liver RNA extracts from adult female mice (8-week-old) subjected to CRS (chronic restraint stress) or CDDP (cisplatin) induced anorexia with or without ACBP/DBI delivery to investigate the impact of ACBP/DBI on anorexia-induced transcriptomic alterations.
2024-07-12 | GSE237766 | GEO
Project description:Bradyrhizobium elkanii USDA 340 genome sequencing
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Project description:To identify functional targets of miR-340, we compared the gene expression profiles of miR-340 overexpressing human GICs with the profiles of their parental cells. The precursor form of miR-340 or control miRNA was overexpressed in glioma cells using miRNA lentiviral particles. The cells were incubated with recombinant virus at 37°C for 12 hr and cultured in the presence of puromycin for 3 days.
2015-04-07 | E-GEOD-61078 | biostudies-arrayexpress
Project description:Anorexia can occur as a serious complication of chronic disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. We studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after an intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6.
2016-05-31 | GSE69151 | GEO
Project description:To identify functional targets of miR-340, we compared the gene expression profiles of miR-340 overexpressing human GICs with the profiles of their parental cells.
2015-04-07 | GSE61078 | GEO
Project description:The goal of this study was to identify accessible chromatin peaks in lamina-associated domains of senescent cells. To establish senescence we used ionizing radiation (IR), overexpression of miR-340-5p, and knockdown of Lamin B Receptor (LBR).One of the cellular processes influenced by microRNAs is senescence, a state of indefinite growth arrest triggered by sublethal cell damage. Here, through bioinformatic analysis and experimental validation, we identified miR-340-5p as a novel miRNA that foments cellular senescence. miR340-5p was highly abundant in diverse senescence models, and miR-340-5p overexpression in proliferating cells rendered them senescent. Among the target mRNAs, miR-340-5p prominently reduced the levels of LBR mRNA, encoding Lamin B Receptor (LBR). Loss of LBR by ectopic overexpression of miR-340-5p derepressed heterochromatin in lamina-associated domains (LADs), promoting the expression of DNA repetitive elements characteristic of senescence. Importantly, overexpressing miR-340-5p enhanced cellular sensitivity to senolytic compounds, while antagonization of miR-340-5p reduced senescent-cell markers and engendered resistance to senolytic-induced cell death. We propose that miR-340-5p can be exploited for clearing senescent cells to restore tissue homeostasis and mitigate damage by senescent cells in aging human pathologies.
2021-06-25 | GSE165465 | GEO