Leptin Signalling in the Ovary of Diet-Induced Obese Mice Regulates Activation of Nod-Like Receptor Protein 3 Inflammasome
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ABSTRACT:
PROVIDER: PRJNA747711 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15182300.fastq.gz | Fastqsanger.gz | |||
| SRR15182301.fastq.gz | Fastqsanger.gz | |||
| SRR15182302.fastq.gz | Fastqsanger.gz | |||
| SRR15182303.fastq.gz | Fastqsanger.gz | |||
| SRR15182304.fastq.gz | Fastqsanger.gz |
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Project description:Obesity leads to ovarian dysfunction and the establishment of local leptin resistance. The aim of our study was to characterise levels of Nod-Like Receptor Protein 3 (NLRP3) inflammasome activation during obesity progression in the mouse ovaries and liver and test the putative role of leptin on its regulation. C57BL/6J mice were treated with equine chorionic gonadotropin (eCG) or human chorionic gonadotropin (hCG) for oestrous cycle synchronisation and ovaries collection. In diet-induced obesity (DIO) model, mice were fed chow diet (CD) or high fat diet (HFD) for 4 or 16 weeks (wk), whereas in hyperleptinemic model (LEPT), mice were injected with leptin for 16 days (16L) or saline (16C) and in the genetic obese leptin-deficient ob/ob (+/? and -/-) animals were fed CD for 4wk. Either ovaries and liver were collected, as well as cumulus cells (CCs) after superovulation from DIO and LEPT. In DIO protocol, protein expression of NLRP3 inflammasome components was increased in 4wk HFD, but decreased in 16wk HFD. Moreover LEPT and ob/ob models revealed NLRP3 and IL-1 upregulation in 16L and downregulation in ob/ob. Transcriptome analysis of CC showed common genes between LEPT and 4wk HFD modulating NLRP3 inflammasome. Moreover analysis in the liver showed upregulation of NLRP3 protein only after 16wk HFD, but also the downregulation of NLRP3 protein in ob/ob-/-. We showed the link between leptin signalling and NLRP3 inflammasome activation in the ovary throughout obesity progression in mice, elucidating the molecular mechanisms underpinning ovarian failure in maternal obesity.
2021-11-01 | GSE180300 | GEO
Project description:Background: Obesity is associated with increased ovarian inflammation and the establishment of local leptin resistance. We presently investigated the role of leptin signalling on Nod-Like Receptor Protein 3 (NLPR3) inflammasome and macrophage prevalence in the pathophysiology of ovarian failure of obese mice. Methods: We collected ovaries from: (i) diet induced obese (DIO) mice fed chow diet (CD) or high-fat diet (HFD) for 4 or 16 weeks (wk); (ii) mice lacking the long-isoform of leptin receptor (ObRb; db/db); (iii) mice lacking leptin (ob/ob); and (iv) pharmacologically hyperleptinemic (LEPT) mice for protein and mRNA expression analysis. Next, granulosa cells (GCs) from antral follicles isolated from db/db and ob/ob mice were subjected to transcriptome analysis. Results: We observed no changes in the mRNA and protein levels of NLRP3 inflammasome components in the ovaries of db/db mice, as well as in markers of M1 and M2 macrophage infiltration. This contrasted with the downregulation of NLRP3 inflammasome components and M1 markers in ob/ob -/- and 16 wk HFD mice. Transcriptional analysis revealed opposing profiles between genetic models, with genes associated with steroid metabolism and prostaglandin action in db/db mice and genes controlling extracellular matrix in ob/ob mice being downregulated, despite both processes being crucial for follicular development and ovulation. Conclusions: Leptin signalling regulated NLRP3 inflammasome activation and expression of M1 markers in ovaries of obese mice, in an ObRb-dependent and -independent manner. Absence of changes in the expression of leptin signalling and proinflammatory mediators in GCs from db/db and ob/ob mice was associated with impaired folliculogenesis.
2024-04-10 | GSE236196 | GEO
Project description:Obesity leads to ovarian dysfunction and the establishment of local leptin resistance. The aim of our study was to characterize the levels of NOD-like receptor protein 3 (NLRP3) inflammasome activation in ovaries and liver of mice during obesity progression. Furthermore, we tested the putative role of leptin on NLRP3 regulation in those organs. C57BL/6J female mice were treated with equine chorionic gonadotropin (eCG) or human chorionic gonadotropin (hCG) for estrous cycle synchronization and ovary collection. In diet-induced obesity (DIO) protocol, mice were fed chow diet (CD) or high-fat diet (HFD) for 4 or 16 weeks, whereas in the hyperleptinemic model (LEPT), mice were injected with leptin for 16 days (16 L) or saline (16 C). Finally, the genetic obese leptin-deficient ob/ob (+/? and -/-) mice were fed CD for 4 week. Either ovaries and liver were collected, as well as cumulus cells (CCs) after superovulation from DIO and LEPT. The estrus cycle synchronization protocol showed increased protein levels of NLRP3 and interleukin (IL)-18 in diestrus, with this stage used for further sample collections. In DIO, protein expression of NLRP3 inflammasome components was increased in 4 week HFD, but decreased in 16 week HFD. Moreover, NLRP3 and IL-1β were upregulated in 16 L and downregulated in ob/ob. Transcriptome analysis of CC showed common genes between LEPT and 4 week HFD modulating NLRP3 inflammasome. Liver analysis showed NLRP3 protein upregulation after 16 week HFD in DIO, but also its downregulation in ob/ob-/-. We showed the link between leptin signaling and NLRP3 inflammasome activation in the ovary throughout obesity progression in mice, elucidating the molecular mechanisms underpinning ovarian failure in maternal obesity.
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Project description:Ovarian leptin signalling regulates NLRP3 inflammasome activation and macrophage infiltration in a cell specific manner
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Project description:Obesity induces profound transcriptome changes in adipocytes; recent evidence suggests that lncRNAs play key roles in this process. Here, we performed a comprehensive transcriptome study by RNA-Seq in adipocytes isolated from interscapular brown, inguinal and epididymal white adipose tissues in diet-induced obese mice. Our analysis reveals a set of obesity-dysregulated lncRNAs, many of which exhibit dynamic changes in fed vs. fasted state, potentially serving as novel molecular markers reflecting adipose energy status. Among the most prominent ones is Lnc-leptin, an lncRNA transcribed from an enhancer region upstream of Leptin. Expression of Lnc-leptin is sensitive to insulin and closely correlates to Leptin expression across diverse pathophysiological conditions. Functionally, induction of Lnc-leptin is essential for adipogenesis, and its presence is required for a loop formation between exon2 of Lnc-leptin and promoter of Leptin in mature adipocytes and the maintenance of Leptin expression in vitro and in vivo. Our study establishes Lnc-leptin as a new regulator of Leptin.
2018-04-19 | GSE113315 | GEO
Project description:Wild type (C57BL/6J) mice were divided in control (W), leptin-treated (E) and pair-fed (F). Obese (ob/ob) mice were divided in control (O), leptin-treated (L) and pair-fed (P). Control (W and O) and pair-fed animals (F and P) received vehicle (PBS), while E and L groups were intraperitoneally administrated with leptin for 28 days. Control (W and O) and leptin-treated (E and L) groups were provided with water and food ad libitum with, while daily food intake of pair fed (F and P) groups were matched to the amount eaten by the leptin-treated groups (E and L) the day before to discriminate the inhibitory effect of leptin on appetite.
2009-09-26 | E-MEXP-1831 | biostudies-arrayexpress
Project description:Modulating leptin sensitivity in hypothalamic neurons is critical for metabolic regulation and plays a key role in the development of obesity. This study examines the effects of three distinct approaches—leptin exposure (LEPA), leptin antagonist administration (LANTA), and palmitate treatment (PA)—on adult-derived mHypoA-2/12 neurons. Transcriptomic analysis using 3' mRNA-Seq revealed significant downregulation of several pathways, including the NOD-like receptor signaling pathway, C-type lectin receptor signaling pathway, NF-κB signaling pathway, and IL-17 signaling pathway. These pathways are closely linked to neuroinflammatory processes, suggesting that modulating leptin sensitivity may influence inflammation in the hypothalamus. The observed downregulation indicates a complex interaction between leptin signaling and cellular stress responses, which may represent an adaptive mechanism to prolonged exposure to leptin or fatty acids. Understanding these dynamics is crucial for gaining insight into how neuroinflammation contributes to the development of leptin resistance and related metabolic disorders.
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Project description:Compare miRNA expression profiles in epididymal adipocytes from normal and leptin deficient obese mice
2009-02-21 | E-MEXP-1789 | biostudies-arrayexpress
Project description:The purpose of this study was to analyze and elucidate the mechanisms of non-obese diabetes-experimental autoimmune encephalomyelitis (NOD-EAE), an animal model of progressive multiple sclerosis (MS), and to compare the pathological features with those observed in human progressive MS. To achieve this, pathological analysis, flow cytometry analysis, immunohistochemical staining, and transcriptome analysis were performed at each pathological stage of the NOD-EAE mice to characterize each pathological stages in the lesion. In the chronic phase of the NOD-EAE mice, fibrosis and lymph follicle formation, characteristic of progressive human MS, were observed. We describe the pathological profile and transcriptome analysis of the NOD-EAE mice and verify that this model has similar features to those of human progressive MS. Our findings suggest that this model recapitulates lymph follicle formation, a disease hallmark of progressive MS, and fibrosis, a feature complicating the pathogenesis of MS in the chronic phase.
2024-04-01 | GSE243235 | GEO
Project description:Axonal growth is limited or absent following peripheral or central nervous system injury respectively, inhibiting repair. The identification of novel growth-promoting molecular mechanisms is therefore a priority. In the search for dietary-dependent mechanisms that control neuronal regenerative ability, we found, via RNA sequencing, that growth-promoting intermittent fasting (IF) induced leptin expression in sensory neurons of the dorsal root ganglia (DRG). Surprisingly, leptin signalling, whose canonical function is to control energy homeostasis, was critical for the IF-dependent regenerative phenotype. In fact, neuronal conditional deletion of the leptin receptor significantly impaired the regenerative response elicited by IF. Overexpression of leptin in vivo in DRG neurons enhanced axonal regeneration following peripheral sciatic nerve crush (SNC) and central spinal cord injury. Lastly, RNA sequencing following leptin overexpression in DRG neurons showed a significant increase in regenerative gene expression and transcription after SCI, indicating a role for leptin in inducing a euchromatic, transcriptionally active environment that facilitates nervous system repair after injury.
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