Thyroid deficiency before birth modifies adipose transcriptome to promote overgrowth of white adipose tissue and impair thermogenic capacity
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB34680 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3568580.fastq.gz | Fastqsanger.gz | |||
| ERR3568590.fastq.gz | Fastqsanger.gz | |||
| ERR3568600.fastq.gz | Fastqsanger.gz | |||
| ERR3568610.fastq.gz | Fastqsanger.gz | |||
| ERR3568620.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 74 |
Similar Datasets
Project description:This study investigates the development of adipose tissue before birth which is crucial for energy storage and thermogenesis in the neonatal period, and for long term metabolic health. The design uses the thyroid deficiency sheep fetus examined at two different gestational ages.
2020-03-31 | E-MTAB-8396 | biostudies-arrayexpress
Project description:Thyroid deficiency before birth modifies adipose transcriptome to promote overgrowth of white adipose tissue and impair thermogenic capacity
2023-06-16 | E-MTAB-8396 | ExpressionAtlas
Project description:Mechanisms that control “beige/brite” thermogenic adipose tissue development may be harnessed to improve human metabolic health. To define these mechanisms, we developed a species-hybrid model in which human mesenchymal progenitor cells were used to develop white or thermogenic/beige adipose tissue in mice. The hybrid adipose tissue developed distinctive features of human adipose tissue, such as larger adipocyte size, despite its neurovascular architecture being entirely of murine origin. Thermogenic adipose tissue recruited a denser, qualitatively distinct vascular network, differing in genes mapping to circadian rhythm pathways, and denser sympathetic innervation. The enhanced thermogenic neurovascular network was associated with human adipocyte expression of THBS4, TNC, NTRK3 and SPARCL1, which enhance neurogenesis, and decreased expression of MAOA and ACHE, which control neurotransmitter tone. Systemic inhibition of MAOA, which is present in human but absent in mouse adipocytes, induced browning of human but not mouse adipose tissue, revealing the physiological relevance of this pathway. Our results reveal species-specific cell type dependencies controlling the development of thermogenic adipose tissue and point to human adipocyte MAOA as a potential target for metabolic disease therapy.
2022-09-27 | GSE200141 | GEO
Project description:Aging impairs the integrated immunometabolic responses which have evolved to maintain core body temperature in homeotherms to survive cold-stress, infections, and dietary restriction. Adipose tissue inflammation regulates the thermogenic stress response but how adipose tissue-resident cells instigate thermogenic failure in the aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2) are lost in aging. Restoration of ILC2 numbers in aged mice to levels seen in adults through IL-33 supplementation failed to rescue old mice from metabolic impairment and increased cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2 are sufficient to protect old mice against cold. Thus, the functional defects in adipose ILC2 during aging drive thermogenic failure.
2021-07-29 | GSE180858 | GEO
Project description:Aging impairs the integrated immunometabolic responses which have evolved to maintain core body temperature in homeotherms to survive cold-stress, infections, and dietary restriction. Adipose tissue inflammation regulates the thermogenic stress response but how adipose tissue-resident cells instigate thermogenic failure in the aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2) are lost in aging. Restoration of ILC2 numbers in aged mice to levels seen in adults through IL-33 supplementation failed to rescue old mice from metabolic impairment and increased cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2 are sufficient to protect old mice against cold. Thus, the functional defects in adipose ILC2 during aging drive thermogenic failure.
2021-07-29 | GSE180910 | GEO
Project description:Defining the lineage of thermogenic perivascular adipose tissue
| PRJNA691058 | ENA
Project description:Background: Development of adipose tissue before birth is essential for energy storage and thermoregulation in the neonate and for cardiometabolic health in later life. Thyroid hormones are important regulators of growth and maturation in fetal tissues. Offspring hypothyroid in utero are poorly adapted to regulate body temperature at birth and are at risk of becoming obese and insulin resistant in childhood. The mechanisms by which thyroid hormones regulate the growth and development of adipose tissue in the fetus, however, are unclear. Methods: This study examined the structure, transcriptome, and protein expression of perirenal adipose tissue (PAT) in a fetal sheep model of thyroid hormone deficiency during late gestation. Proportions of unilocular (UL) (white) and multilocular (ML) (brown) adipocytes, and UL adipocyte size, were assessed by histological and stereological techniques. Changes to the adipose transcriptome were investigated by RNA sequencing and bioinformatic analysis, and proteins of interest were quantified by Western blotting. Results: Hypothyroidism in utero resulted in elevated plasma insulin and leptin concentrations and overgrowth of PAT in the fetus, specifically due to hyperplasia and hypertrophy of UL adipocytes with no change in ML adipocyte mass. RNA sequencing and genomic analyses showed that thyroid deficiency affected 34% of the genes identified in fetal adipose tissue. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways were associated with adipogenic, metabolic, and thermoregulatory processes, insulin resistance, and a range of endocrine and adipocytokine signaling pathways. Adipose protein levels of signaling molecules, including phosphorylated S6-kinase (pS6K), glucose transporter isoform 4 (GLUT4), and peroxisome proliferator-activated receptor γ (PPARγ), were increased by fetal hypothyroidism. Fetal thyroid deficiency decreased uncoupling protein 1 (UCP1) protein and mRNA content, and UCP1 thermogenic capacity without any change in ML adipocyte mass. Conclusions: Growth and development of adipose tissue before birth is sensitive to thyroid hormone status in utero. Changes to the adipose transcriptome and phenotype observed in the hypothyroid fetus may have consequences for neonatal survival and the risk of obesity and metabolic dysfunction in later life.
| S-EPMC7286741 | biostudies-literature
Project description:Adipose tissues, particularly beige and brown adipose tissue, play crucial roles in energy metabolism. Brown adipose tissues’ thermogenic capacity and the appearance of beige cells within white adipose tissue have spurred interest in their metabolic impact and therapeutic potential. Brown and beige fat cells, activated by factors like cold exposure, share mechanisms that drive non-shivering thermogenesis. Understanding their behavior requires sophisticated, yet universal in vitro models that replicate the complex microenvironment and vasculature of adipose tissues. Here we present mouse vascularized adipose spheroids of the stromal vascular microenvironment from inguinal white adipose tissue. We show that scaffold embedding improves vascular sprouting, enhances spheroid growth, and upregulates adipogenic markers. Transcriptional profiling via RNA sequencing revealed distinct metabolic pathways upregulated in our vascularized adipose spheroids, with increased expression of genes involved in glucose metabolism, lipid metabolism, and thermogenesis. Functional assessment demonstrated increased oxygen consumption in vascularized adipose spheroids compared to 2D cultures, which was further enhanced by β-adrenergic receptor stimulation via isoproterenol correlating with elevated β-adrenergic receptor expression. Moreover, stimulation with the naturally occurring adipokine, FGF21, induced Ucp1 mRNA expression in the vascularized adipose spheroids. In conclusion, our vascularized inguinal white adipose tissue spheroids provide a physiologically relevant platform to study how the stromal vascular microenvironment shapes adipocyte responses and influence activated thermogenesis in beige adipocytes.
2024-05-02 | GSE261267 | GEO
Project description:The physiological adaptation to cold environmental temperatures involves the remodeling of energy-storing white adipose tissue (WAT) into an energy-burning thermogenic phenotype, characterized by the emergence of multi-locular beige adipocytes. To date, the full array of cold-responsive cells within WAT that mediate thermogenic remodeling remain undefined. Here, we demonstrate that distinct perivascular PDGFRb+ adipocyte precursor cell (APC) subpopulations are differentially sensitive to cold temperatures in vivo. One day of cold exposure elicits striking transcriptional changes in DPP4+ PDGFRb+ APCs, whereas committed DPP4- PDGFRb+ preadipocytes appear comparatively much less responsive. This adaptation includes beta-adrenergic receptor mediated induction in the expression of the pro-thermogenic cytokine, IL-33. DPP4+ PDGFRb+ cells represent the sole source of IL-33 within inguinal WAT of adult mice. Doxycycline-inducible deletion of Il33 in PDGFRb+ cells at the onset of cold exposure significantly compromises the thermogenic remodeling of WAT without directly impacting the differentiation capacity of APCs per se. Together, these studies reveal the presence of a cold-responsive progenitor cell subpopulation in adult WAT and highlight their ability to regulate tissue plasticity through the production of immunological factors.
2021-11-09 | GSE165974 | GEO
Project description:Brown adipose tissue (BAT) is a thermogenic organ that requires Uncoupling Protein 1 (UCP1) to dissipate chemical energy as heat, to defend core body temperature against hypothermia, and counteract obesity and metabolic diseases1. However, the transcriptional mechanism ensuring BAT thermogenic capacity for survival prior to environmental cold is unknown. Here we show histone deacetylase 3 (HDAC3) is a required transcriptional regulator of BAT enhancers to ensure thermogenic aptitude and survival. Mice with genetic ablation of HDAC3 become severely hypothermic and fail to survive acute cold exposure. UCP1 is nearly absent in BAT lacking HDAC3 and there is marked down-regulation of mitochondrial oxidative phosphorylation (OXPHOS) genes. Remarkably, although HDAC3 canonically functions as a transcriptional corepressor2, HDAC3 functions as a coactivator of the estrogen-related receptor _ (ERR_) in BAT, and loss of HDAC3 leads to robust global down-regulation of ERR±-driven enhancers. HDAC3 coactivation of ERR_ is mediated through deacetylation of PGC-1_ and is required for basal transcription of Ucp1, OXPHOS, and Pgc-1_. Thus, HDAC3 uniquely primes Ucp1 and thermogenic gene transcription to ensure immediate BAT-driven thermogenesis upon acute exposure to dangerously cold temperatures.
2017-06-14 | GSE83927 | GEO