RNA-seq analysis of the effects of forskolin treatment on human primary adipocytes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE129153 | GEO | 2021/01/27
REPOSITORIES: GEO
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Project description:We studied the role of the cAMP responsive factor CREB in promoting insulin resistance following its activation in adipose under obese conditions; We identified genes that were upregulated in primary cultures of mouse adipocytes following exposure to forskolin; and we characterized genes that are also induced in white adipose tissue in mice maintained on a high fat diet. Experiment Overall Design: Primary cultures of mouse adipocytes,harvested from visceral adipose tissue, were exposed to forskolin (10uM) or vehicle control (DMSO) for 2 hours. White adipose tissue (epididymal fat pads) were collected from mice maintained on a 60% high fat diet for 12 weeks and from control mice on normal chow.
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Project description:Analysis of gene expression levels of HER2-positive breast cancer cells exposed to the conditioned medium from adipocytes. The hypothesis tested in the present study was that adipocytes secrete factors that induce the resistance of cancer cells to antibody-dependent cellular cytotoxicity mediated by trastuzumab. The results provide insight into the genes that may be involved in the adipocyte-induced cancer resistance to trastuzumab treatment. BT474 cells or SKBR3 cells were exposed to the conditioned medium (CM) from differentiated hMADS (#hMADS) or to the control medium for 2 h. Total RNA was extracted and analyzed. The experiment was performed in triplicate.
2015-04-01 | E-GEOD-52660 | biostudies-arrayexpress
Project description:Multiple myeloma is characterized by osteolytic lesions caused by osteoclast-mediated bone resorption and reduced bone formation. A unique feature of myeloma is a failure of bone healing following successful treatment. Identification of increased adipocyte numbers in marrow of successfully treated patients led us to demonstrate that normal marrow adipocytes, when co-cultured with myeloma cells, are reprogrammed and produce adipokines that activate osteoclastogenesis and suppress osteoblastogenesis. These adipocytes have reduced expression of peroxisome proliferator-activated receptor (PPAR) mediated by recruitment of polycomb-repressive complex 2 (PRC2) via specificity protein 1, which modifies PPAR promoter methylation at trimethyl lysine-27 histone H3. We confirmed the importance of PPAR methylation by demonstrating that adipocyte-specific knockout of EZH2, a member of the PRC2, prevents adipocyte reprogramming and reverses bone changes in vivo. These results define a heretofore unrecognized role for adipocytes in genesis of myeloma-associated bone disease and that reversal of adipocyte reprogramming has therapeutic implications.
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Project description:Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWAT). Both cold- and iAdFASNKO-induced iWAT “browning” pathways upregulate the sympathetic nerve fiber (SNF) modulator Nrg4 and activate SNFs adjacent to beige adipocytes. Adipocyte cAMP/protein kinase A signaling is necessary for beige adipocyte appearance, as we show here it is blocked in Gsa deficient cold exposed or iAdFASNKO mice. Surprisingly however, denervation of iWAT failed to block adipocyte browning in iAdFASNKO mice, as it does in cold-exposed mice. Similarly, Nrg4 deficiency markedly reduced iWAT UCP1 in the cold, but not in double FASN/Nrg4 KO mice. Single-cell transcriptomic analysis of iWAT stromal cells revealed increased macrophages displaying gene expression signatures of the alternately activated type in iAdFASNKO mice, and their depletion abrogated iWAT beiging. Altogether, these findings reveal divergent cellular pathways are sufficient to cause adipocyte browning. Importantly, adipocyte signaling to enhance alternatively activated macrophages in iAdFASNKO mice is associated with enhanced adipose thermogenesis independent of the sympathetic neuron involvement this process requires in the cold.
2020-08-18 | GSE154047 | GEO
Project description:Brown adipose tissue is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs as essential regulators of brown adipocyte differentiation, but it remains unknown whether microRNAs are required for the feature maintenance of mature brown adipocytes. To address this question, we ablated Dgcr8, a key regulator of the microRNA biogenesis pathway, in mature brown as well as white adipocytes. The adipose tissue -specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat, and the mice were intolerant to cold exposure. In vitro primary brown adipocyte cultures confirmed that microRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that microRNAs are essential for the browning of subcutaneous white adipocyte both in vitro and in vivo. Using this animal model, we performed microRNA expression profiling analysis and identified a set of BAT-specific microRNAs that are up-regulated during brown adipocyte differentiation and enriched in brown fat compared to other organs. We identified miR-182 and miR-203 as new regulators of brown adipocyte development. Taken together, our study demonstrates an essential role of microRNAs in the maintenance as well as the differentiation of brown adipocytes. TotalRNAs were extracted using a Qiagen kit, and 5 M-NM-<g of total RNAs for each sample were used to prepare the mRNA- Seq library according to the manufacturerM-bM-^@M-^Ys instruction (NEB). cDNA libraries were prepared and sequenced by Hi-seq in Whitehead Genome Core. 2 replicates of each treatment were analyzed.
2014-08-07 | E-GEOD-60165 | biostudies-arrayexpress
Project description:We have identified a population of adipocytes in fat tissue that arise from bone marrow-derived progenitor cells. We used microarrays to compare the global gene expression patterns of the bone marrow progenitor-derived adipocytes as well as conventional white and brown adipocytes to evaluate the relationship between these adipocyte subpopulations. Gonadal fat tissue (for white adipocytes) and intrascapular fat tissue (for brown adipocytes) was digested with collagenase and adipocytes were recovered by centrifugation/flotation. Bone marrow derived adipocytes were isolated from the adipocyte fraction of gonadal fat tissue from mice receiving bone marrow tranplants from donors expressing either green fluorescent protein (GFP) or beta-galactosidase (LacZ) by flow cytometry.
2010-01-08 | E-GEOD-19757 | biostudies-arrayexpress
Project description:Brown adipose tissue is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs as essential regulators of brown adipocyte differentiation, but it remains unknown whether microRNAs are required for the feature maintenance of mature brown adipocytes. To address this question, we ablated Dgcr8, a key regulator of the microRNA biogenesis pathway, in mature brown as well as white adipocytes. The adipose tissue -specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat, and the mice were intolerant to cold exposure. In vitro primary brown adipocyte cultures confirmed that microRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that microRNAs are essential for the browning of subcutaneous white adipocyte both in vitro and in vivo. Using this animal model, we performed microRNA expression profiling analysis and identified a set of BAT-specific microRNAs that are up-regulated during brown adipocyte differentiation and enriched in brown fat compared to other organs. We identified miR-182 and miR-203 as new regulators of brown adipocyte development. Taken together, our study demonstrates an essential role of microRNAs in the maintenance as well as the differentiation of brown adipocytes.
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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.
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Project description:This study analyzed the differentiation and polarization of human monocytes regulated by factors released from adipocytes (termed adipokines) at the gene expression level. The hypothesis was that adipokines affect differentiation and M1/M2 polarization of human monocytes. Results revealed interesting up- and down-regulated genes related to the differentiation and M1/M2 polarization of human monocytes in response to adipokines.
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