The muscle-enriched myokine Musclin impairs beige fat thermogenesis and systemic energy homeostasis via Tfr1/PKA signaling in male mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE228218 | GEO | 2023/03/27
REPOSITORIES: GEO
Similar Datasets
Project description:Tfr1 is important for iron uptake in red blood cells. We deleted Tfr1 in skeletal muscle to determine the role of Tfr1 in iron uptake in skeletal muscle. We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle
2015-05-08 | GSE68675 | GEO
Project description:We deleted Tfr1 in the heart to determine the role of Tfr1 in iron uptake in normal cardiac funciton We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle
2015-05-12 | GSE68745 | GEO
Project description:We deleted Tfr1 in the heart to determine the role of Tfr1 in iron uptake in normal cardiac funciton We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle We isolated RNA from WT and Tfr1 KO hearts at both postnatal day 5 and postnatal day 10.RNA was labaled and hibridized to Affymetrics microarrays.
2015-05-12 | E-GEOD-68745 | biostudies-arrayexpress
Project description:Tfr1 is important for iron uptake in red blood cells. We deleted Tfr1 in skeletal muscle to determine the role of Tfr1 in iron uptake in skeletal muscle. We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle We used skeletal muscle and liver from wild type and Tfr1 skeletal muscle KO mice at postnatal day 5 and postnatal day 9. mRNA was extracted from the tissues, labaled and hibridized to Affymetrics microarrays.
2015-05-08 | E-GEOD-68675 | biostudies-arrayexpress
Project description:We report that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, beige adipocyte differentiation and activation. Mechanistically, Naa10p acetylates the N-terminus of Pgc1-alpha and prevents it from interacting with Ppar[gamma] to activate key genes, such as Ucp1, involved in beige adipocyte function.
2019-08-15 | GSE133726 | GEO
Project description:We reported that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, beige adipocyte differentiation and activation. Mechanistically, Naa10p acetylates the N-terminus of Pgc1α and prevents it from interacting with Ppar to activate key genes, such as Ucp1, involved in beige adipocyte function. We used microarrays to profile the gene expression changes by Naa10p KO in inguinal white adipose tissues (iWATs) derived from mice fed with high fat diet for 15 weeks.
2019-08-16 | GSE133865 | GEO
Project description:Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression in brown and beige adipocytes and that SUV420H2 knockdown significantly reduces, whereas SUV420H2 overexpression significantly increases UCP1 levels in brown adipocytes. Suv420h2 knockout (H2KO mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study showed that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) promoter, leading to down-regulated expression of 4E-BP1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.
2024-05-09 | GSE244457 | GEO
Project description:H-ferritin (HFn) nanocarrier is emerging as a promising theranostic platform for tumor diagnosis and therapy, which can specifically target tumor cells via binding transferrin receptor 1 (TfR1). This led us to investigate the therapeutic function of TfR1 in GC. The clinical significance ofTfR1 was assessed in 178 GC tissues using a magneto-HFn nanoparticle-based immunohistochemistry method. Therapeutic effects of doxorubicin-loaded HFn nanocarriers evaluated on TfR1 positive GC patient-derived xenograft (GC-PDX) models. The biological function of TfR1 was investigated through in vitro and in vivo assays. TfR1 was upregulated (73.03%) in GC tissues and reversely correlated with patient outcome. TfR1 negative sorted cells exhibited tumor-initiating feature, which enhanced tumor formation in vitro and in vivo, migration/invasion, whereas TfR1 positive sorted cells showed significant proliferation ability. Knockout of TfR1 in GC cells also enhanced cell invasion. TfR1 deficient cells displayed immune escape by upregulating PD-L1, CXCL9 and CXCL10, when disposed by IFN-γ. Western blot results demonstrated that knockout of TfR1 in GC cells upregulated Akt and STAT3 signaling. Moreover, in TfR1 positive GC-PDX models, HFn-Dox group significantly inhibited tumor growth and increased mouse survival compared with that of free-Dox group. TfR1 could be a potential prognostic and therapeutic biomarker for GC: (i) TfR1 reversely correlated with patient outcome and its negative cells possess tumor aggressive features; (ii) TfR1 positive cells can be killed by H-ferritin nanocarrier. Given the heterogeneity of GC, HFn nanocarrier combined with other therapies towards TfR1 negative cells (such as: small molecule or immunotherapy etc.) will be new options for GC treatment.
2023-01-01 | GSE143497 | GEO
Project description:Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression in brown and beige adipocytes and that SUV420H2 knockdown significantly reduces, whereas SUV420H2 overexpression significantly increases UCP1 levels in brown adipocytes. Suv420h2 knockout (H2KO mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study showed that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) promoter, leading to down-regulated expression of 4E-BP1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.
2024-05-09 | GSE245509 | GEO
Project description:Interorgan crosstalk via secreted hormones and metabolites is a fundamental aspect of mammalian metabolic physiology. Beyond the highly specialized endocrine cells, peripheral tissues are emerging as an important source of metabolic hormones that influence energy and nutrient metabolism and contribute to disease pathogenesis. Neuregulin 4 (Nrg4) is a fat-derived hormone that protects mice from nonalcoholic steatohepatitis (NASH) and NASH-associated liver cancer by shaping hepatic lipid metabolism and the liver immune microenvironment. Despite its enriched expression in brown fat, whether NRG4 plays a role in thermogenic response and mediates the metabolic benefits of cold exposure remain unexplored. Here we show that Nrg4 expression in inguinal white adipose tissue (iWAT) is highly responsive to chronic cold exposure. Nrg4 deficiency impairs beige fat induction and renders mice more susceptible to diet-induced metabolic disorders under mild cold conditions. Using mice with adipocyte and hepatocyte-specific Nrg4 deletion, we reveal that adipose tissue-derived NRG4, but not hepatic NRG4, is essential for beige fat induction following cold acclimation. Furthermore, treatment with recombinant NRG4-Fc fusion protein promotes beige fat induction in iWAT and improves metabolic health in diet-induced obese mice. These findings highlight a critical role of NRG4 in mediating beige fat induction and preserving metabolic health under mild cold conditions.
2024-01-01 | GSE246993 | GEO