Impact of changing mice housing temperature on glucocorticoids' effects on different adipose tissue depots
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE212349 | GEO | 2022/09/04
REPOSITORIES: GEO
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Project description:Interplay between parenchymal energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of cellular origin or specialized niche, adipocytes require the activity of the nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ, however, the molecular mechanisms by which PPARγ licenses white adipose tissue (WAT) to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ-long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity (DIO). Pharmacologic inhibition or genetic deletion of the lncRNA Lexis, enhances UCP-1 dependent and independent thermogenesis. Adipose tissue specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT signaling that preserves white adipose tissue plasticity.
2023-09-27 | GSE216608 | GEO
Project description:Interplay between parenchymal energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of cellular origin or specialized niche, adipocytes require the activity of the nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ, however, the molecular mechanisms by which PPARγ licenses white adipose tissue (WAT) to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ-long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity (DIO). Pharmacologic inhibition or genetic deletion of the lncRNA Lexis, enhances UCP-1 dependent and independent thermogenesis. Adipose tissue specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT signaling that preserves white adipose tissue plasticity.
2023-09-27 | GSE216272 | GEO
Project description:Interplay between parenchymal energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of cellular origin or specialized niche, adipocytes require the activity of the nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ, however, the molecular mechanisms by which PPARγ licenses white adipose tissue (WAT) to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ-long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity (DIO). Pharmacologic inhibition or genetic deletion of the lncRNA Lexis, enhances UCP-1 dependent and independent thermogenesis. Adipose tissue specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT signaling that preserves white adipose tissue plasticity.
2023-09-27 | GSE215870 | 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 | GSE169672 | 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 | GSE169669 | 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:Canonical WNT pathway in mature adipocytes exacerbates obesity. In this study, we constructed UCP1-positive adipocytes-specific Ctnnb1 knockout mice (UBKO) and observed increased “browning” of white adipose tissue (WAT) following cold exposure or CL-316,243 administration compared to controls. UBKO mice also displayed increased energy expenditure. Furthermore, β-catenin (encoded by Ctnnb1) inhibited thermogenic genes expression in differentiated beige adipocytes and repressed Ucp1 expression at transcription level. Transcriptome analysis revealed UBKO mice treated with CL-316,243 had enhanced mitochondrial function and downregulated immunerelated genes in WAT. Improved glucose tolerance and insulin sensitivity were observed in 50-week-old UBKO mice. Public datasets indicated CTNNB1 expression inversely correlated with several thermogenic genes expression in human adipose/adipocytes, and positively correlated with body mass index (BMI) or waist-hip ratio (WHR). We proposed that intervention of β-catenin in adipocytes could be an effective strategy to enhance energy expenditure and improve age-related metabolic performance.
2023-03-31 | GSE227415 | GEO
Project description:In the last decades, adipose tissue has been defined to play a central role in the control of energy balance. Furthermore, the proven endocrine and thermogenic functions of adipocytes have renewed interest in the study of this tissue, as the activation of non-shivering thermogenesis may hold great potential for the future treatment of obesity and T2D. Cold exposure has defined to activate this process. Here, the miRNA transcriptomic response of epididymal and inguinal white adipose depots (eWAT and iWAT, respectively) as well as that of the interscapular brown adipose depot (iBAT) of C57Bl/6 mice either exposed to 22ºC or 4ºC for the period of 4 days were examined. This in-detail study of the adaptation of each depot to cold exposure has allowed unraveling depot-specific regulatory molecular mechanisms.
2021-10-28 | E-MTAB-8966 | biostudies-arrayexpress
Project description:In the last decades, adipose tissue has been defined to play a central role in the control of energy balance. Furthermore, the proven endocrine and thermogenic functions of adipocytes have renewed interest in the study of this tissue, as the activation of non-shivering thermogenesis may hold great potential for the future treatment of obesity and T2D. Cold exposure has defined to activate this process. Here, the transcriptomic response of epididymal and inguinal white adipose depots (eWAT and iWAT, respectively) as well as that of the interscapular brown adipose depot (iBAT) of C57Bl/6 mice either exposed to 22ºC or 4ºC for the period of 4 days were examined. This in-detail study of the adaptation of each depot to cold exposure has allowed unraveling depot-specific regulatory molecular mechanisms.
2022-02-06 | E-MTAB-8965 | biostudies-arrayexpress
Project description:Objectives Intermittent fasting is an effective dietary intervention to combat metabolic disease. Here, we explore the adipose depot specific response to every-other-day fasting (EODF) in mice to identify mechanisms that underly the beneficial effects. Methods Male C57BL/6J mice were placed on a 12-day EODF or ad libitum diet, after which tissues were harvested including visceral (vWAT) and subcutaneous (scWAT) white adipose tissue, as well as brown adipose tissue (BAT), which was then analysed by unbiased mass spectrometry-based proteomics. Results After EODF treatment, pathway enrichment analysis of our dataset showed that both WAT depots showed increased mitochondrial protein content, with scWAT also showing increased UCP1, but mitochondrial protein content was decreased in BAT. This effect on mitochondria is correlated to the increased abundance of proteins involved in glycolysis, pyruvate metabolism, the TCA cycle and fatty acid synthesis in both WAT depots. Furthermore, EODF-treated mice downregulated the lipolysis pathway in vWAT including a 5-fold decrease in the abundance of the beta3 adrenergic receptor (ADRB3). Enrichment analysis lso revealed that vWAT of EODF treated mice had significantly reduced ECM proteins, which lowers the inflammatory potential of this organ. Our adipose depot proteomic survey also allowed us to identify depot-enriched protein expression, such as the vWAT enrichment for the AKAP12 protein related to PKA signalling that was down-regulated by EODF treatment. Conclusions These findings show how the adipose depots have adapted to the EODF regime to preserve the lipid store, with the most striking changes occurring in the vWAT depot to downregulate the lipolysis pathway and induce expression of pathways needed for fatty acid synthesis. This substrate cycling and reduced inflammatory potential of the adipose tissue may contribute to the improved insulin sensitivity observed in these animals.
2022-10-12 | PXD020255 | Pride