Similar Datasets
Project description:Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the limiters of energy expenditure are largely unknown. Here, we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to differentiation, obesity, and aging. Assay for transposase-accessible chromatin sequencing (ATAC-seq), ChIP-seq, and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and C/EBPβ recruitment to key enhancer regions. These findings expand our understanding of the relationship between inflammatory signaling pathways and adipose tissue function and provide insight into the physiological control of thermogenesis that could inform future therapy.
| S-EPMC5766418 | biostudies-literature
Project description:Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the physiologic limiters of energy expenditure are largely unknown. Here we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and mature adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to cold, obesity and aging. ATAC-seq and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and PGC-1alpha recruitment to key enhancer regions. These findings identify the IL-10 axis as a critical and potentially targetable regulator of thermogenesis, and expand our understanding of the links between inflammatory signaling and adipose tissue function in the setting of obesity.
2018-01-28 | GSE94651 | GEO
Project description:Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the physiologic limiters of energy expenditure are largely unknown. Here we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and mature adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to cold, obesity and aging. ATAC-seq and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and PGC-1alpha recruitment to key enhancer regions. These findings identify the IL-10 axis as a critical and potentially targetable regulator of thermogenesis, and expand our understanding of the links between inflammatory signaling and adipose tissue function in the setting of obesity.
2018-01-28 | GSE94653 | GEO
Project description:Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the physiologic limiters of energy expenditure are largely unknown. Here we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and mature adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to cold, obesity and aging. ATAC-seq and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and PGC-1alpha recruitment to key enhancer regions. These findings identify the IL-10 axis as a critical and potentially targetable regulator of thermogenesis, and expand our understanding of the links between inflammatory signaling and adipose tissue function in the setting of obesity.
2018-02-27 | GSE111208 | GEO
Project description:IL-10 signaling remodels adipose chromatin architecture to limit thermogenesis and energy expenditure
| PRJNA371736 | ENA
Project description:IL-10 signaling remodels adipose chromatin architecture to limit thermogenesis and energy expenditure [ChIP-Seq]
| PRJNA436164 | ENA
Project description:Brown adipose tissue plays a central role in the regulation of the energy balance by expending energy to produce heat. NAD+-dependent deacylase sirtuins have widely been recognized as positive regulators of brown adipose tissue thermogenesis. However, here we reveal that SIRT7, one of seven mammalian sirtuins, suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions. Whole-body and brown adipose tissue-specific Sirt7 knockout mice have higher body temperature and energy expenditure. SIRT7 deficiency increases the protein level of UCP1, a key regulator of brown adipose tissue thermogenesis. Mechanistically, we found that SIRT7 deacetylates insulin-like growth factor 2 mRNA-binding protein 2, an RNA-binding protein that inhibits the translation of Ucp1 mRNA, thereby enhancing its inhibitory action on Ucp1. Furthermore, SIRT7 attenuates the expression of batokine genes, such as fibroblast growth factor 21. In conclusion, we propose that SIRT7 serves as an energy-saving factor by suppressing brown adipose tissue functions.
| S-EPMC9744749 | biostudies-literature
Project description:The goal of this study was to define the functional role of adipocyte-specific expression of the RNA binding protein Human antigen R (HuR). Mice with an adipocyte-specific deletion of HuR (Adipo-HuR-/- ) were generated by crossing HuR floxed (HuRfl/fl ) mice with mice expressing adiponectin-driven cre-recombinase (Adipoq-cre). Our results show that Adipo-HuR-/- mice display a lean phenotype compared to wild-type littermate controls. HuR deletion results in a diet-independent reduction in percent body fat composition along with an increase in energy expenditure. Functionally, Adipo-HuR-/- mice show a significant impairment in acute adaptive thermogenesis (six hours at 4°C), but uncoupling protein 1 (UCP1) protein expression in brown adipose tissue (BAT) is unchanged compared to control. Pharmacological inhibition of HuR also results in a marked decline in core body temperature following acute cold challenge independent of UCP1 protein expression. Among the 588 HuR-dependent genes in BAT identified by RNA-seq analysis, gene ontology analysis shows a significant enrichment in mediators of calcium transport and signalling, almost all of which are decreased in Adipo-HuR-/- mice compared to control. In conclusion, adipocyte expression of HuR plays a central role in metabolic homoeostasis and mediates UCP1-independent thermogenesis in BAT, potentially through post-transcriptional control of intracellular calcium transport.Abbreviations: Adipo-HuR-/-: Adipocyte-specific HuR deletion mice; BAT: Brown adipose tissue; HuR: Human antigen R; UCP1: Uncoupling protein 1.
| S-EPMC7469577 | biostudies-literature
Project description:Adipose thermogenesis plays a pivotal role in whole-body metabolic homeostasis. Although transcriptional mechanisms that promote thermogenesis are extensively studied, the negative regulatory network is still poorly understood. Here, a Krüppel-associated box (KRAB) domain-containing zinc finger protein, ZFP961, as a potent repressor of the thermogenic program is identified. ZFP961 expression is induced by cold and β3-adrenergic agonist in adipose tissue. ZFP961 represses brown fat-selective gene expression and mitochondrial respiration without any effect on general adipogenesis in cultured adipocytes. Adipose-specific knockdown and overexpression of ZFP961 produce remarkable and opposite phenotypes of white fat remodeling. ZFP961 knockout mice display robust inguinal white adipose tissue browning, which is abolished by reexpression of full-length ZFP961, but not by KRAB domain-deleted ZFP961 mutant. ZFP961-deficient mice are cold tolerant and resistant to high-fat diet-induced obesity, hyperglycemia, and hepatic steatosis. ZFP961 suppresses thermogenic gene expression by directly interacting with PPARα and blocking its transcriptional activity, which can be completely negated by the PPARα agonist. The findings uncover ZFP961 as a critical physiological brake that limits adipose thermogenesis and provides insights into the regulatory mechanisms that maintain energy balance and tissue homeostasis.
| S-EPMC8805557 | biostudies-literature
Project description:Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning.
| S-EPMC4994119 | biostudies-literature