Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343814 | ENA |
REPOSITORIES: ENA
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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: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:Caloric restriction (CR) and methionine restriction driven enhanced lifespan and healthspan induces ‘browning’ of white adipose tissue (WAT), a metabolic response that increases heat production to defend core-body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight-loss induced by CR in humans reduces thiol-containing sulfur amino acid cysteine in WAT. Systemic cysteine-depletion in mice causes lethal weight-loss with increased fat utilization and browning of adipocytes that is rescued upon restoration of cysteine in diet. Mechanistically, cysteine restriction induced adipose browning and weight-loss requires sympathetic nervous system derived noradrenaline signaling via β3-adrenergic-receptors that is independent of FGF21 and UCP1. In obese mice, cysteine deprivation induced rapid adipose browning, increased energy expenditure leading to 30% weight-loss and reversed metabolic inflammation. These findings establish that cysteine is essential for organismal metabolism as removal of cysteine in the host triggers adipose browning and rapid weight loss.
2025-05-22 | GSE293660 | GEO
Project description:Caloric restriction (CR) and methionine restriction driven enhanced lifespan and healthspan induces ‘browning’ of white adipose tissue (WAT), a metabolic response that increases heat production to defend core-body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight-loss induced by CR in humans reduces thiol-containing sulfur amino acid cysteine in WAT. Systemic cysteine-depletion in mice causes lethal weight-loss with increased fat utilization and browning of adipocytes that is rescued upon restoration of cysteine in diet. Mechanistically, cysteine restriction induced adipose browning and weight-loss requires sympathetic nervous system derived noradrenaline signaling via β3-adrenergic-receptors that is independent of FGF21 and UCP1. In obese mice, cysteine deprivation induced rapid adipose browning, increased energy expenditure leading to 30% weight-loss and reversed metabolic inflammation. These findings establish that cysteine is essential for organismal metabolism as removal of cysteine in the host triggers adipose browning and rapid weight loss.
2025-05-22 | GSE292788 | 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: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:Two types of UCP1 positive cells-brown and beige adipocytes exist in mammals. Beige adipocytes are very plastic, and can be dynamically regulated by environment.Beige adipocytes formed postnatally in subcutaneous inguinal white adipose tissue (iWAT) lost thermogenic gene expression and multilocular morphology at adult stage, but cold could restore their “beigeing” characteristics, a phenomenon termed as beige adipocyte renaissance. Our results showed that beige cell maintenance and renaissance in adult mice were regulated by cAMP and HDAC4 signaling in white adipocytes non-cell autonomously. Genetic modulations of various components of this cAMP-HDAC4 cascade (e.g. LKB1) led to persistent browning and reduced adiposity independent of thermogenesis. To further study the mechanisms of beige adipocytes maintenance, we performed RNA-seq with samples from inguinal white adipose tissues of WT, AdipoqCre LKB1 F/F, and AdipoqCre LKB1 F/F; HDAC4 F/F mice.Our studies will move the beige adipocyte field forward and attract clinical applications to target beige adipocyte renaissance.
2018-02-14 | GSE85335 | GEO
Project description:Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medical therapies. Emerging evidences have suggested a crosstalk between adipose tissue and vascular cells and brown adipose tissue is beneficial for cardiovascular health. Nevertheless, whether brown remodeling of white adipose tissue would protect against AAA remains unclear. Here we showed that patients with AAA had a decreased browning level of adipose tissue and induction of adipose tissue browning significantly reduced AAA incidence and attenuated AAA development in mice. Using LC-MS/MS and proteomic analysis, we further identified Follistatin-like 1 (FSTL1) as a novel vessel-protective adipokine secreted by browning adipocytes. Mechanistically, FSTL1 inhibited VSMC apoptosis through DIP2A/AKT signaling. Furthermore, we demonstrated that adipocyte-specific deficiency of FSTL1 abrogated the protective effect of browning induction. Moreover, supplementation of FSTL1 either systemically or patched into hydrogel placing around abdominal aorta markedly limited aortic dilation and AAA progression. Our data suggest a protective role of adipose tissue browning and a novel batokine FSTL1 in the development of AAA, which may represent a novel intervention strategy for AAA.
2025-09-07 | PXD064197 | Pride
Project description:A strong association between leucine and obesity has been well established; however, the role of leucine catabolic enzymes in adipose tissue remains largely unknown. Here, we show that knockdown of the leucine catabolic enzyme AU RNA binding methylglutaconyl-CoA hydratase (AUH) in brown adipocytes reduces thermogenesis, while AUH over-expression has the opposite effect both in vivo and in vitro. Mechanistically, AUH partially promotes uncoupling protein 1 (UCP1) expression through its metabolite 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA). HMG-CoA directly HMGylates peroxisome proliferator-activated receptor gamma (PPARγ) on lysine 386, enhancing its transcriptional activity to increase UCP1 expression. In addition, AUH binds to and stabilizes Ucp1 mRNA via its RNA-binding function. Moreover, we discover that AUH promotes white adipose tissue browning; AUH expression in human white adipose tissue is inversely correlated with adiposity, and over-expression of AUH in adipose tissue protects mice against high-fat diet-induced obesity. Collectively, these results provide new insights into the crosstalk between amino acid metabolism and thermogenesis and identify a novel post-translational modification of PPARγ.
2026-03-09 | PXD075390 |
Project description:Expression data from browning inguinal white adipose tissue in UCP1/ApoE-DKO mice
| PRJNA376526 | ENA