SnRNA-seq of Beiging Inguinal Adipose Tissue from UCP1-KO and WT mice under cold-stress and mice treated with Beta-Blocker and mild cold exposure.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE174497 | GEO | 2021/05/17
REPOSITORIES: GEO
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Project description:snRNA-seq of Beiging Inguinal Adipose Tissue from UCP1-KO and WT mice under cold-stress and mice treated with Beta-Blocker and mild cold exposure.
| PRJNA730278 | ENA
Project description:Single cell level analysis of transcriptional circuits regulating UCP1-indepednent theremogensis through Lgr6 in inguinal Adipose tissue. We previously identified an increase in Lgr6 gene expression in the beige adipocyte population of UCP1-KO mice and hypothesized its involvement in UCP1-independent thermogensis. Consistent with our previous data the scATAC-seq data reveals that chromatin accessibility at the Lgr6 loci is significantly higher in Ucp1- KO beige adipocytes as compared to WT and the promter is also more accessible in Ucp1- KO beige adipocytes. Other DNA-binding motifs involved in UCP-1 indepedent thermogensis were also analyzed and found to be upregulated in the KO model.
2021-05-15 | GSE174456 | GEO
Project description:Differentiation of brown adipocytes is a crucial process for adaptive thermogenesis, which is stimulated by various factors. We found robust browning of inguinal white adipose tissue in UCP1/ApoE-DKO mice, but not in ApoE-KO mice, under high-fat diet condition. We used microarray to determine the genes specifically regulated in the browning white adipose tissue in UCP1/ApoE-DKO mice.
2018-10-01 | GSE95273 | GEO
Project description:Although various stimuli and mediators have been identified to promote thermogenic beige fat development, less is known about the negative regulator of cold-induced beiging. We here show that lack of chemerin that is highly expressed in white adipose tissue or its receptor CMKLR1 in adipocytes enhances cold-induced beiging and thermogenesis. Our results reveal a previously unrecognized beige-inhibitory role of chemerin-CMKLR1 axis, and suggests CMKLR1 as a therapeutic target for obesity-related metabolic disorders.
2019-12-31 | GSE133978 | GEO
Project description:Non-shivering thermogenesis in adipocytes is mediated by brown adipose tissue, purportedly through the sole action of uncoupling protein 1 (UCP1). The physiological relevance of UCP1-dependent thermogenesis has primarily been inferred from the attenuation of thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1-/-). However, germline Ucp1-/- mice harbor secondary changes within brown adipose tissue beyond UCP1, such as reduced electron transport chain abundance. We show here that these secondary changes also encompass reduced expression of genes regulating fuel liberation, changes that would attenuate the capacity of any thermogenic pathway. Therefore, the quantitative contribution of UCP1-dependent and -independent thermogenesis is not fully understood. To mitigate the potentially confounding ancillary changes to brown adipose tissue of germline Ucp1-/- mice, we constructed mice with inducible adipocyte-selective disruption of Ucp1. We find that, while germline Ucp1-/- mice succumb to cold-induced hypothermia with complete penetrance, most mice with inducible deletion of Ucp1 maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletion of Ucp1 and creatine kinase B (Ckb, an effector of UCP1-independent thermogenesis) exacerbates cold-intolerance, indicative of a negative genetic interaction and thus a parallel thermogenic function. We find no evidence for impairments in insulation or non-shivering thermogenesis in skeletal muscle that would drive this phenotype. Furthermore, following UCP1 deletion or UCP1/CKB co-deletion from mature adipocytes, moderate cold exposure triggers the regeneration of mature adipocytes that coordinately restore UCP1 and CKB to brown adipose tissue, providing further evidence of their parallel thermogenic relationship. Our findings suggest that thermogenic adipocytes utilize non-paralogous protein redundancy – through UCP1 and CKB – to promote cold-induced energy dissipation.
2024-01-10 | PXD047841 | Pride
Project description:Global RNA sequencing analysis of the hypothalamus, BAT, inguinal WAT and muscle of long-term cold exposed WT, FGF21 KO, UCP1 KO and UCP1/FGF21 double KO mice
2017-08-16 | GSE99412 | GEO
Project description:The induction of beige adipocytes in white adipose tissue (WAT), also known as WAT beiging, improves glucose and lipid metabolism. However, the regulation of WAT beiging at the posttranscriptional level remains elusive. Here, we report that METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging in mice. Adipose-specific depletion of Mettl3 gene undermines WAT beiging. Transcriptomic analysis of m6A modifications and mRNA expression level reveals global reduction of m6A-modified mRNAs in Mettl3-depleted beige adipose tissue. In particular, METTL3-catalyzed m6A installation on Krüppel-like factor 9 (Klf9) mRNA prevents its degradation. We further demonstrate that the m6A reader protein IGF2BP3 mediates the stabilization of m6A-modified Klf9 mRNA. Overexpressioin of KLF9 protein reverses the impaired WAT beiging elicited by Mettl3 deletion. These findings uncover a novel epitranscriptional mechanism in WAT beiging and identify METTL3-KLF9 axis as a potential therapeutic target for obesity-associated disorders.
2023-02-03 | GSE178884 | GEO
Project description:Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we showed that vascular injury induced the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulated in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbated inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuated inflammation and pathological vascular remodeling. Single-cell RNA sequencing revealed that beige adipocytes abundantly expressed neuregulin 4 (Nrg4) which critically regulated alternative macrophage activation. Importantly, significant beiging was observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induced the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitated alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrated the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.
2022-06-21 | GSE206399 | GEO
Project description:Abstract
Brown and brite adipocytes are the key cells performing uncoupling protein 1 (UCP1) dependent non-shivering thermogenesis (NST) induced by cold exposure. Several lipid species are associated to NST in brown and white adipose tissue. Studies investigating the association of the lipid profile with NST rely on the analysis of whole organ homogenates or on the differentiation of pre-adipocytes in vitro. These approaches have so far not addressed the heterogeneity of white adipose tissue. Aim of this study was to characterize the lipid composition of white adipose tissue on a region-specific level in an in vivo context.
We applied MALDI mass spectrometry imaging (MALDI-MSI) in combination with immunohistochemistry and high-resolution mass spectrometry on sections of inguinal white adipose tissue of 129S6/SvEvTac and C57BL6/N-UCP1 knockout and wildtype mice acclimatized to cold to identify lipids specific to areas of UCP1 expression.
Based on the analysis of cold exposed 129S6/SvEvTac mice we identified cardiolipins (CL) and diacylglycerols (DG) species to be specific for areas expressing UCP1 and triacylglycerols (TG) to be the main lipid class characteristic for UCP1 negative regions within inguinal white adipose tissue. Investigation of C57BL6/N-UCP1 knockout and wildtype mice housed at either room temperature or acclimatized to cold, demonstrated that CL content in white adipose tissue is increased upon cold stimulation, independent of UCP1.
We introduce a MALDI-MSI based approach to identify lipids associated to thermogenic adipocytes in adipose tissues demonstrating a clear regional cold dependent upregulation of CL independent of UCP1.
2021-04-07 | MSV000087164 | MassIVE
Project description:Mice expressing Cas9 were administered AAV8-UCP1 sgRNA to the brown adipose tissue for inducible knockout. Mice were housed at 22ºC for two weeks and then were sacrificed. Brown adipose tissue (BAT) was harvested and RNAseq was performed to determine transcriptional changes stemming from inducible UCP1 knockout.
2021-07-01 | GSE176453 | GEO