Transplantation of Committed Pre-adipocytes from Brown Adipose Tissue improves Whole-body Glucose Homeostasis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1051988 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27198011_1.fastq.gz | Fastqsanger.gz | |||
| SRR27198011_2.fastq.gz | Fastqsanger.gz | |||
| SRR27198012_1.fastq.gz | Fastqsanger.gz | |||
| SRR27198012_2.fastq.gz | Fastqsanger.gz | |||
| SRR27198013_1.fastq.gz | Fastqsanger.gz |
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Project description:Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2-4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed ‘committed pre-adipocytes’ from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.
2023-12-13 | GSE250078 | GEO
Project description:Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2-4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed "committed pre-adipocytes" from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling, and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.
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Project description:Prolonged cold exposure stimulates the recruitment of beige adipocytes within white adipose tissue. Beige adipocytes depend on mitochondrial oxidative phosphorylation to drive thermogenesis. The transcriptional mechanisms that promote remodeling in adipose tissue during the cold are not well understood. Here we demonstrate that the transcriptional coregulator transducin-like enhancer of split 3 (TLE3) inhibits mitochondrial gene expression in beige adipocytes. Conditional deletion of TLE3 in adipocytes promotes mitochondrial oxidative metabolism and increases energy expenditure, thereby improving glucose control. Using chromatin immunoprecipitation and deep sequencing, we found that TLE3 occupies distal enhancers in proximity to nuclear-encoded mitochondrial genes and that many of these binding sites are also enriched for early B-cell factor (EBF) transcription factors. TLE3 interacts with EBF2 and blocks its ability to promote the thermogenic transcriptional program. Collectively, these studies demonstrate that TLE3 regulates thermogenic gene expression in beige adipocytes through inhibition of EBF2 transcriptional activity. Inhibition of TLE3 may provide a novel therapeutic approach for obesity and diabetes.
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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.
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Project description:Loss of TLE3 promotes the mitochondrial program in beige adipocytes and improves glucose metabolism
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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.
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2018-09-04 | PXD009280 | Pride
Project description:Lymphoid committed CD34+lin-CD10+CD24- progenitors undergo a rebound at month 3 after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the absence of acute graft-versus-host disease (aGVHD). Here, we analyzed transcriptional programs of cell-sorted circulating lymphoid committed progenitors and CD34+Lin-CD10- non lymphoid progenitors in 11 allo-HSCT patients having (n=5) or not developed (n=6) grade 2 or 3 aGVHD and in 7 age-matched healthy donors. Major deregulated pathways included protein synthesis, energy production, cell cycle regulation and cytoskeleton organization. Notably, genes from protein biogenesis, translation machinery and cell cycle (CDK6) were over-expressed in progenitors from patients in the absence of aGVHD compared with healthy donors and patients affected by aGVHD. Expression of many genes from the mitochondrial oxidative phosphorylation metabolic pathway leading to ATP production were more specifically increased in lymphoid committed progenitors in absence of aGVHD. This was also the case for genes involved in cell mobilization such as those regulating Rho GTPases activity. In all, we show that circulating lymphoid committed progenitors undergo profound changes in metabolism favoring cell proliferation, energy production and cell mobilization after allo-HSCT in humans. These mechanisms are abolished in case of aGVHD or its treatment, indicating a persistent cell-intrinsic defect after exit from bone marrow.
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Project description:Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.
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