Effect of orthotopically transplanted pancreatic tumor on gene expression of subcutaneous white adipose tissue.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE274804 | GEO | 2026/03/17
REPOSITORIES: GEO
Similar Datasets
Project description:We performed transcriptomic profiling for two models of adipose browning, the classical mouse model and our newly described great roundleaf bat (H. armiger) model. Transcriptomes were generated from subcutaneous adipose tissue (sWAT), intra-abdominal adipose tissue (aWAT) and interscapular BAT (iBAT) from male and female bats, as well as sWAT and iBAT from male and female mice, which were acclimatized to 10°C and 30°C. These 20 trascriptomes allowed us to identity genes, GO terms, and pathways that show significant expression changes and are shared by both species during the browning process.
2018-07-12 | GSE72603 | GEO
Project description:Timed-feeding leads to adipose browning, although the integrative mechanisms for the same remain unclear. Here we show that twice-a-nocturnal (TAN) feeding causes biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed-feeding. Insulin and leptin surges lead to marked cellular, functional and metabolic remodeling of sWAT resulting in increased energy expenditure. Single-cell RNAseq analyses and flow cytometry reveal a role for insulin and leptin surges in ILC2 recruitment and sWAT browning, since depleting leptin or blocking insulin receptor signaling or ILC2 cell recruitment, each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day co-injections is sufficient to favorably remodel innervated sWAT. Indeed, innervation is necessary for sWAT remodeling since denervation of sWAT, but not BAT, blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, timed feeding reorganizes nutrient-sensitive pathways to remodel sWAT, which drives the metabolic benefits of timed-feeding.
2024-04-17 | GSE264173 | GEO
Project description:Timed-feeding leads to adipose browning, although the integrative mechanisms for the same remain unclear. Here we show that twice-a-nocturnal (TAN) feeding causes biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed-feeding. Insulin and leptin surges lead to marked cellular, functional and metabolic remodeling of sWAT resulting in increased energy expenditure. Single-cell RNAseq analyses and flow cytometry reveal a role for insulin and leptin surges in ILC2 recruitment and sWAT browning, since depleting leptin or blocking insulin receptor signaling or ILC2 cell recruitment, each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day co-injections is sufficient to favorably remodel innervated sWAT. Indeed, innervation is necessary for sWAT remodeling since denervation of sWAT, but not BAT, blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, timed feeding reorganizes nutrient-sensitive pathways to remodel sWAT, which drives the metabolic benefits of timed-feeding.
2024-04-15 | GSE263899 | 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:In acute cold stress in mammals, JMJD1A, an H3K9 demethylase, up-regulates thermogenic gene expressions through β-adrenergic signaling in brown adipose tissue (BAT). Aside BAT-driven thermogenesis, mammals also have another mechanism to cope with long-term cold stress by inducing the browning of subcutaneous white adipose tissue (scWAT). Here, we show that this occurs through a two-step process that requires both β-adrenergic dependent phosphorylation of S265 and demethylation of H3K9me2 by JMJD1A. The histone demethylation independent acute Ucp1 induction in BAT and demethylation dependent chronic Ucp1 expression in beige-scWAT provide complementary molecular mechanisms to ensure an ordered transition between acute and chronic adaptation to cold stress. JMJD1A mediates two major signaling pathways, namlely β-adrenergic receptor and PPARγ activation, via PRDM16-PPARγ-P-JMJD1A complex for beige adipogenesis.
2018-02-16 | GSE107900 | GEO
Project description:Hypoxic conditions in high-altitude environments present unique physiological stressors that drive metabolic adaptations, including adipose tissue browning. In this study, we investigated whether hypoxia (11.6% O₂, simulating 5,300 m altitude) could independently induce browning of adipose tissue in mice, apart from cold-induced mechanisms. Hypoxia significantly promoted the formation of multilocular adipocytes in inguinal white adipose tissue (iWAT) and upregulated thermogenic genes (UCP1, PGC-1α, Cox4i1, VEGF), glucose metabolism-related genes (IRS1/2, PDK2, PPARα), and beige adipocyte markers (Car4, UCP1). In contrast, interscapular brown adipose tissue (iBAT) showed minimal response to hypoxia, with no significant change in UCP1 expression. Notably, hypoxia elevated both Nrg4 and phosphorylated ErbB4 in iWAT. In vitro, Nrg4 overexpression in 3T3-L1 adipocytes increased the expression of PKAcα, PGC-1α, and UCP1, while pharmacological inhibition of ErbB4 phosphorylation using Dacomitinib attenuated Nrg4- and hypoxia-induced browning and lipolysis. In vivo, Dacomitinib treatment impaired hypoxia-mediated improvements in WAT browning and glucose tolerance. To explore the structural basis of this interaction, molecular docking and 100-ns molecular dynamics simulations were conducted, revealing strong and stable binding between Nrg4 and ErbB4, with calculated binding energies of −174.26 kcal/mol (MM/GBSA) and −19.5 kcal/mol (PRODIGY). These findings collectively demonstrate that the Nrg4–ErbB4 axis plays a central role in mediating hypoxia-induced browning and metabolic reprogramming of WAT, providing mechanistic insight into adipose tissue plasticity under low-oxygen conditions.
2025-06-11 | GSE298931 | GEO
Project description:Obesity causes insulin resistance, and PPARγ ligands like rosiglitazone (rosi) are insulin-sensitizing, yet mechanisms remain unclear. High fat diet (HFD) induced obesity has major effects on visceral epididymal adipose tissue (eWAT) of C57BL/6 (B6) mice, and here we report altered activity of gene regulatory elements with changes in PPARγ genome-wide occupancy. Treatment with rosi restored insulin sensitivity, yet surprisingly had little effect on eWAT, leading us to consider the subcutaneous inguinal fat (iWAT). In this depot, rosi markedly induced molecular signatures of brown fat including the key thermogenic gene Ucp1. Obesity-resistant 129S1/SvImJ (129) mice showed this degree of iWAT browning even in the absence of rosi. Remarkably, the 129 Ucp1 locus had increased PPARγ binding and gene expression that was preserved in B6x129 F1 intercross iWAT, with imbalance favoring the 129-derived alleles showing a cis-acting genetic difference. Thus, B6 mice have a genetic defect in Ucp1 expression. However, imbalanced expression favoring 129 over B6 was nearly lost when Ucp1 was activated by rosi, or by iWAT browning in cold-exposed or young mice. These results provide a novel framework for understanding how environmental influences like drugs can rescue genetically determined disease phenotypes by affecting the epigenome.
2017-02-27 | GSE92606 | GEO
Project description:Obesity causes insulin resistance, and PPARγ ligands like rosiglitazone (rosi) are insulin-sensitizing, yet mechanisms remain unclear. High fat diet (HFD) induced obesity has major effects on visceral epididymal adipose tissue (eWAT) of C57BL/6 (B6) mice, and here we report altered activity of gene regulatory elements with changes in PPARγ genome-wide occupancy. Treatment with rosi restored insulin sensitivity, yet surprisingly had little effect on eWAT, leading us to consider the subcutaneous inguinal fat (iWAT). In this depot, rosi markedly induced molecular signatures of brown fat including the key thermogenic gene Ucp1. Obesity-resistant 129S1/SvImJ (129) mice showed this degree of iWAT browning even in the absence of rosi. Remarkably, the 129 Ucp1 locus had increased PPARγ binding and gene expression that was preserved in B6x129 F1 intercross iWAT, with imbalance favoring the 129-derived alleles showing a cis-acting genetic difference. Thus, B6 mice have a genetic defect in Ucp1 expression. However, imbalanced expression favoring 129 over B6 was nearly lost when Ucp1 was activated by rosi, or by iWAT browning in cold-exposed or young mice. These results provide a novel framework for understanding how environmental influences like drugs can rescue genetically determined disease phenotypes by affecting the epigenome.
2017-02-27 | GSE91067 | GEO
Project description:Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage tracing mouse studies revealed that adipocytes from sWAT would migrate into the wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested beige adipocytes in sWAT abundantly express neuregulin 4 (Nrg4) which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.
2023-11-21 | GSE247964 | GEO
Project description:In acute cold stress in mammals, JMJD1A, an H3K9 demethylase, up-regulates thermogenic gene expressions through β-adrenergic signaling in brown adipose tissue (BAT). Aside BAT-driven thermogenesis, mammals also have another mechanism to cope with long-term cold stress by inducing the browning of subcutaneous white adipose tissue (scWAT). Here, we show that this occurs through a two-step process that requires both β-adrenergic dependent phosphorylation of S265 and demethylation of H3K9me2 by JMJD1A. The histone demethylation independent acute Ucp1 induction in BAT and demethylation dependent chronic Ucp1 expression in beige-scWAT provide complementary molecular mechanisms to ensure an ordered transition between acute and chronic adaptation to cold stress. JMJD1A mediates two major signaling pathways, namlely β-adrenergic receptor and PPARγ activation, via PRDM16-PPARγ-P-JMJD1A complex for beige adipogenesis.
2018-02-16 | GSE107899 | GEO