Claudin-1 as a novel target gene induced in obesity and associated to inflammation, fibrosis and cell differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE236145 | GEO | 2024/04/03
REPOSITORIES: GEO
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Project description:Objectives Intermittent fasting is an effective dietary intervention to combat metabolic disease. Here, we explore the adipose depot specific response to every-other-day fasting (EODF) in mice to identify mechanisms that underly the beneficial effects. Methods Male C57BL/6J mice were placed on a 12-day EODF or ad libitum diet, after which tissues were harvested including visceral (vWAT) and subcutaneous (scWAT) white adipose tissue, as well as brown adipose tissue (BAT), which was then analysed by unbiased mass spectrometry-based proteomics. Results After EODF treatment, pathway enrichment analysis of our dataset showed that both WAT depots showed increased mitochondrial protein content, with scWAT also showing increased UCP1, but mitochondrial protein content was decreased in BAT. This effect on mitochondria is correlated to the increased abundance of proteins involved in glycolysis, pyruvate metabolism, the TCA cycle and fatty acid synthesis in both WAT depots. Furthermore, EODF-treated mice downregulated the lipolysis pathway in vWAT including a 5-fold decrease in the abundance of the beta3 adrenergic receptor (ADRB3). Enrichment analysis lso revealed that vWAT of EODF treated mice had significantly reduced ECM proteins, which lowers the inflammatory potential of this organ. Our adipose depot proteomic survey also allowed us to identify depot-enriched protein expression, such as the vWAT enrichment for the AKAP12 protein related to PKA signalling that was down-regulated by EODF treatment. Conclusions These findings show how the adipose depots have adapted to the EODF regime to preserve the lipid store, with the most striking changes occurring in the vWAT depot to downregulate the lipolysis pathway and induce expression of pathways needed for fatty acid synthesis. This substrate cycling and reduced inflammatory potential of the adipose tissue may contribute to the improved insulin sensitivity observed in these animals.
2022-10-12 | PXD020255 | Pride
Project description:Human adipose stem and progenitor cells (ASPCs) develop into heterogenous cultures of adipogenic and Structural Wnt-regulated Adipose Tissue resident (SWAT) cells upon induction of adipogenic differentiation. In vitro proliferating ASPC and differentiating adipocytes were collected from multiple timepoints to identify the trajectory of cells. Cells from two white depots (subcutaneous abdominal & visceral abdominal) and two brown depots (supraclavicular & perirenal) were used for the study. Progenitors from all 4 depots show similar differentiation trajectories during early differentiation.
2023-04-03 | GSE227635 | GEO
Project description:Exosomes derived from adipose tissues (AT-Exos) have been identified as a crucialmedium in the transmission of information from adipose tissue to itself and to other organs, including exosomes derived from inguinal white adipose tissue (iWAT-Exos), visceral white adipose tissue (vWAT-Exos) and brown adipose tissue (BAT-Exos). However, the functional differences in depot-specific AT-Exos under obese conditions remain elusive. Here we reported that AT-Exos participated in regulating adipocyte inflammation and metabolic homeostasis. Notably, vWAT-Exos play a critical role in promoting lipid accumulation and inflammation in the development of obesity. Although both are derived from “energy storage” WAT, the biological effects exhibited by iWAT-Exos are far different from those vWAT-Exos. Especially under diet-induced obesity conditions, iWAT-Exos appeared to be BAT-Exo-like, exhibiting an “energy expending” type. Altogether, our data indicated that AT-Exos from different depots have distinct functions and effects on adipocytes metabolism.
2024-04-25 | GSE264480 | GEO
Project description:Background: Claudin-1(CLDN1), one of the key components of tight junction proteins, was found to be down-regulated in human lung adenocarcinomas. This study we investigated the clinical significance of CLDN1 expression in lung adenocarcinoma patients and its role in cancer progression. Method: CLDN1 mRNA expression was measured in tumor specimens from 51 patients with lung adenocarcinoma. CLDN1 protein expression was also examined by immunohistochemistry on specimens from an independent cohort of 67 lung adenocarcinoma patients. CLDN1 and cancer cell migration, invasion, and in vivo metastasis were studied by compared CLDN1 overexpressed, specific shRNA knockdown cells and controls. The Affymetrix oligonucleotide microarray analysis was performed to identify CLDN1 downstream genes. Results: Lung adenocarcinoma patients with low expression of CLDN1 mRNA had shorter overall survival (p = 0.032, log-rank test). This result was further confirmed by immunohistochemistry of CLDN1 protein expression in an independent cohort of lung adenocarcinoma patients (p=0.024). Over-expression of CLDN1 inhibited lung adenocarcinoma cell migration, invasion, and in vivo metastasis. Knockdown of the exogenous CLDN1 expression in CLDN1 transfectants can restore the cancer cell invasive and metastatic ability. By using Affymetrix microarray we have identified panel of genes altered by CLDN1 over-expression. CLDN1 can up-regulate several cancer invasion/metastasis suppressors such as CTGF, THBS1, DLC1, OCLN, ZO-1, and also down-regulate invasion/metastasis enhancers such as SPP1, CUTL1, TGF-α, SLC2A3, PGF, which support that CLDN1 may behave as an invasion and metastasis suppressor. Conclusions: CLDN is a cancer invasion and metastasis suppressor. CLDN1 expression is a useful prognostic predictor and a potential drug treatment target for lung adenocarcinoma patients. Keywords: genetic modification
2008-12-23 | GSE10309 | GEO
Project description:Human adipose stem and progenitor cells (ASPCs) develop into heterogenous cultures of adipogenic and Structural Wnt-regulated Adipose Tissue resident (SWAT) cells upon induction of adipogenic differentiation. To investiagte the function of SWAT cells and compare them with proliferating ASPCs, we enriched the SWAT cells from the adipogenic cells using density gradient centriguation. The enriched SWAT cells were cultured for 24 hours in proliferation media or differentiation media for 24 hours. 4 density gradient centrifugations were performed, resulting in 4 technical replicates per media type. We included proliferating ASPCS (undifferentiated) as control. We then performed gene expression profiling analysis using data from RNA-Seq of 4 samples per condition (proliferating ASPCs, SWAT cells in proliferation media, SWAT cells in differentiation media)
2023-04-03 | GSE223588 | GEO
Project description:Obesity-driven pathological expansion of white adipose tissue (WAT) is a key driver of endothelial dysfunction. Contrary to this paradigm, early vascular alterations associated with over nutrition also exacerbate AT dysfunction. To dissect this complex cause and consequence relationship, here we perform a single-cell transcriptomics screen to generate a detailed landscape of endothelial heterogeneity and vascular alterations in murine model of obesity. Given the differences in ontogeny and function of distinct WAT depots, we demarcate key differences in subcutaneous and visceral WAT vasculature. In addition to descriptive taxonomy, we perform in-depth validation and characterization of our in silico data. We identify a sWAT specific fenestrated endothelial cell subtype, which is drastically reduced in obese conditions. This reduction was associated with a decrease in VEGFA expressing perivascular cells. The novel endothelial subtypes provide a basis for future research and new directions for therapeutic interventions.
2023-05-26 | E-MTAB-12855 | biostudies-arrayexpress
Project description:The blood-brain barrier (BBB) is a multicellular neurovascular unit (NVU) that allows the selective passage of necessary molecules into the central nervous system (CNS), while limiting the entry of neurotoxins and most drugs. A crosstalk with pericytes and neural cells mediates the acquisition of specialized properties, such as the formation of tight junctions (TJs), in brain microvascular endothelial cells (BMECs). TJs limit the paracellular passage of solutes, thereby regulating CNS homeostasis. However, the mechanisms by which NVU cells communicate to mediate TJ formation remains a mystery. Retinoic acid (RA), a key signaling molecule during vertebrate embryonic development, is commonly used to enhance functional barrier properties in in vitro BBB models. However, its physiological relevance and affected pathways are not fully understood.
2022-08-01 | GSE202485 | GEO
Project description:The Nod like receptor protein 3 (NLRP3) inflammasome and its product interleukin-1β (IL-1β) drive inflammaging in visceral adipose tissue (vWAT) and contribute to the expansion of interleukin-1 receptor 1 (Il1r1) positive aged adipose B-cells (AABs). AABs promote metabolic dysfunction and inflammation under inflammatory challenges. However, it is unclear whether IL-1β contributes to AAB-associated inflammation during aging. Using a B-cell specific knockout of Il1r1 (BKO mice), we characterized old vWAT in the absence of IL-1β – B-cell signaling. In addition to sex-specific metabolic improvements in females, we identified a reduction in the proportion of B-cells and a sex-specific increase in the B1:B2 B-cell ratio in BKO vWAT. Using single cell RNA-sequencing of vWAT immune cells, we observed that BKO differentially affected inflammatory signaling in vWAT immune cells. These data suggest that IL-1β – B-cell signaling supports the inflammatory response in multiple cell types and provides insight into the complex microenvironment in aged vWAT.
2024-11-19 | GSE274935 | 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:Obesity causes type 2 diabetes, cardiovascular diseases, NAFLD, and cancer, but all fat is not equal as subcutaneous white adipose tissue (SWAT) is more metabolically favorable than visceral fat. Here, we investigate mTORC2 function in SWAT growth by deleting its essential subunit Rictor in SWAT precursor cells and examining its effect on adipocyte differentiation and tissue development. We found that Rictor/mTORC2 is not required for SWAT preadipocyte differentiation per se; however, SWAT preadipocytes differentiating without Rictor cannot fully induce the lipid storage transcriptional program. In vivo, this results in smaller adipocytes, reduced SWAT size, lipid re-distribution to visceral and brown fat, and gender-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes PPARg activity towards specific lipid metabolism genes independently of ChREBP, but in coordination, to set the lipid handling capacity of SWAT. Further exploring this pathway may uncover new strategies to stimulate lipid storage in more metabolically favorable SWAT.
2020-10-06 | GSE146470 | GEO