Obesity-instructed TREM2-high macrophages identified by comparative analysis of diabetic mouse and human kidney at single-cell resolution [scRNA-seq: DKD_mouse]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE205592 | GEO | 2024/10/29
REPOSITORIES: GEO
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Project description:The expression of adipogenic genes is decreased in obesity and diabetes mellitus ; Samuel T. Nadler*, Jonathan P. Stoehr*, Kathryn L. Schueler*, Gene Tanimoto, Brian S. Yandell, and Alan D. Attie*,§ ; Departments of * Biochemistry, and Statistics and Horticulture, University of Wisconsin, Madison, WI, 53706; and Affymetrix, Inc., Santa Clara, CA 95051 ; Communicated by Neal L. First, University of Wisconsin, Madison, WI, July 13, 2000 (received for review April 3, 2000) ; Obesity is strongly correlated with type 2 diabetes mellitus, a common disorder of glucose and lipid metabolism. Although adipocytes are critical in obesity, their role in diabetes has only recently been appreciated. We conducted studies by using DNA microarrays to identify differences in gene expression in adipose tissue from lean, obese, and obese-diabetic mice. The expression level of over 11,000 transcripts was analyzed, and 214 transcripts showed significant differences between lean and obese mice. Surprisingly, the expression of genes normally associated with adipocyte differentiation were down-regulated in obesity. Not all obese individuals will become diabetic; many remain normoglycemic despite profound obesity. Understanding the transition to obesity with concomitant diabetes will provide important clues to the pathogenesis of type 2 diabetes. Therefore, we examined the levels of gene expression in adipose tissue from five groups of obese mice with varying degrees of hyperglycemia, and we identified 88 genes whose expression strongly correlated with diabetes severity. This group included many genes that are known to be involved in signal transduction and energy metabolism as well as genes not previously examined in the context of diabetes. Our data show that a decrease in expression of genes normally involved in adipogenesis is associated with obesity, and we further identify genes important for subsequent development of type 2 diabetes mellitus. Experiment Overall Design: For obesity study, lean samples include C57BL/6J lean, (C57BL/6J X BTBR) F1 and BTBR lean, obese sampples incluse C57BL/6J-ob/ob, (C57BL/6J X BTBR) F2-ob/ob and BTBR-ob/ob. All samples are subjected to Mu11K A and B arrays. Experiment Overall Design: For diabetes study, B6-ob/ob, (C57BL/6J X BTBR) F2-ob/ob low glucose, (C57BL/6J X BTBR) F2-ob/ob medium glucose, (C57BL/6J X BTBR) F2-ob/ob high glucose, and BTBR-ob/ob samples were analyzed for genes whose expression levels changes correlated with the plasma glucose levels in these mice. All samples are subjected to Mu11K A and B arrays.
2007-12-04 | E-GEOD-2952 | biostudies-arrayexpress
Project description:Obesity is a strong risk factor for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased. When made genetically obese, the BTBR mouse strain is diabetes susceptible and the C57BL/6J (B6) strain is diabetes resistant. We used DNA microarrays and RT-PCR to compare the gene expression in BTBR-ob/ob versus B6-ob/ob mice in adipose tissue, liver, skeletal muscle, and pancreatic islets. Our results show: 1) there is an increased expression of genes involved in inflammation in adipose tissue of diabetic mice; 2) lipogenic gene expression was lower in adipose tissue of diabetes-susceptible mice, and it continued to decrease with the development of diabetes, compared with diabetes-resistant obese mice; 3) hepatic expression of lipogenic enzymes was increased and the hepatic triglyceride content was greatly elevated in diabetes-resistant obese mice; 4) hepatic expression of gluconeogenic genes was suppressed at the prediabetic stage but not at the onset of diabetes; and 5) genes normally not expressed in skeletal muscle and pancreatic islets were expressed in these tissues in the diabetic mice. We propose that increased hepatic lipogenic capacity protects the B6-ob/ob mice from the development of type 2 diabetes. Diabetes 52:688â700, 2003 Experiment Overall Design: Four B6-ob/ob and four BTBR-ob/ob male mice at 14 weeks of age were used in the microarray study. RNA samples from two individuals were pooled for each tissue, and each pooled RNA sample was applied to an Affymetrix MGU74AV2 array. Because of the scarcity of islets in the BTBR-ob/ob mice, 4 additional mice were pooled to obtain islet RNA from these animals. Sixteen MGU74Av2 arrays (2 strains X 4 tissues X 2 replicates = 16 arrays) were used to monitor the expression level of â12,000 genes or ESTs.
2007-08-31 | E-GEOD-2899 | biostudies-arrayexpress
Project description:Obesity is a strong risk factor for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased. When made genetically obese, the BTBR mouse strain is diabetes susceptible and the C57BL/6J (B6) strain is diabetes resistant. We used DNA microarrays and RT-PCR to compare the gene expression in BTBR-ob/ob versus B6-ob/ob mice in adipose tissue, liver, skeletal muscle, and pancreatic islets. Our results show: 1) there is an increased expression of genes involved in inflammation in adipose tissue of diabetic mice; 2) lipogenic gene expression was lower in adipose tissue of diabetes-susceptible mice, and it continued to decrease with the development of diabetes, compared with diabetes-resistant obese mice; 3) hepatic expression of lipogenic enzymes was increased and the hepatic triglyceride content was greatly elevated in diabetes-resistant obese mice; 4) hepatic expression of gluconeogenic genes was suppressed at the prediabetic stage but not at the onset of diabetes; and 5) genes normally not expressed in skeletal muscle and pancreatic islets were expressed in these tissues in the diabetic mice. We propose that increased hepatic lipogenic capacity protects the B6-ob/ob mice from the development of type 2 diabetes. Diabetes 52:688–700, 2003 Keywords: Genetic modifications
2005-07-12 | GSE2899 | GEO
Project description:We found that 18-week administration of a prolyl hydroxylase inhibitor, enarodustat, improved glucose/lipid metabolism of BTBR ob/ob mice, which is a model of obesity and type 2 diabetes mellitus. Enarodustat-treated mice also exhibited reduced albuminuria along with ameliorated glomerular epithelial and endothelial damage. In order to elucidate the mechanism of renoprotection, we performed microarray gene expression analysis of isolated glomeruli. The initial screening process revealed 8965 probes whose absolute values of log2 (BTBR ob/ob mice treated with enarodustat/BTBR ob/ob mice treated with vehicle-only) exceeded 0.5. We then compared the expression levels of those 8965 probes between BTBR ob/ob and wild-type mice to identify molecules that were likely to be involved in the pathogenesis of glomerular injury. Such analysis revealed 71 genes which were significantly up-regulated and 47 genes which were significantly down-regulated in BTBR ob/ob mice compared to wild-type mice. The genes were ranked according to their fold-change values, and the analysis presented Ccl2/Mcp1 as the second-most up-regulated gene in BTBR ob/ob mice. The expression level of Ccl2/Mcp1 increased by 24.42-fold in BTBR ob/ob compared to wild-type mice, and its expression in enarodustat-treated BTBR ob/ob mice was decreased to 0.62 of the vehicle-only treated BTBR ob/ob mice. Urinary CCL2/MCP-1 was indeed decreased in enarodustat-treated BTBR ob/ob mice. In vitro experiments also showed that enarodustat suppressed palmitate-induced CCL2/MCP-1 production in murine mesangial cells. Taken together, enarodustat is likely to confer renoprotection through regulating the expression of CCL2/MCP-1 in the glomerulus.
2020-04-17 | GSE131266 | GEO
Project description:To investigate the gene expression levels of major glomerular cell types in BTBR ob/ob mice and in glomeruli under hyperfiltration Bulk RNA-sequencing of glomerular cell types from BTBR ob/ob and BTBR +/+ mice at three time points (6/12/18 weeks). The glomeruli were isolated from ex vivo perfused kidney (hyperfiltration) and unperfused kidney (control) from the mouse.
2022-11-21 | GSE218086 | GEO
Project description:The gastrointestinal (GI) tract can have significant impact on the regulation of the whole body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analyses in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, both obese mouse groups had significant amount of gene expression changes in the stomach (ob/ob: 959; HFD: 542), much more than the number of changes in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes and insulin resistance. In addition, the gene expression profile strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity.
2016-06-15 | GSE69306 | GEO
Project description:single-cell RNA sequencing of renal cells from type 2 diabetes mice (BTBR ob/ob) at the early stage of DN.
2022-11-29 | GSE218563 | GEO
Project description:Background: Obesity is associated with increased ovarian inflammation and the establishment of local leptin resistance. We presently investigated the role of leptin signalling on Nod-Like Receptor Protein 3 (NLPR3) inflammasome and macrophage prevalence in the pathophysiology of ovarian failure of obese mice. Methods: We collected ovaries from: (i) diet induced obese (DIO) mice fed chow diet (CD) or high-fat diet (HFD) for 4 or 16 weeks (wk); (ii) mice lacking the long-isoform of leptin receptor (ObRb; db/db); (iii) mice lacking leptin (ob/ob); and (iv) pharmacologically hyperleptinemic (LEPT) mice for protein and mRNA expression analysis. Next, granulosa cells (GCs) from antral follicles isolated from db/db and ob/ob mice were subjected to transcriptome analysis. Results: We observed no changes in the mRNA and protein levels of NLRP3 inflammasome components in the ovaries of db/db mice, as well as in markers of M1 and M2 macrophage infiltration. This contrasted with the downregulation of NLRP3 inflammasome components and M1 markers in ob/ob -/- and 16 wk HFD mice. Transcriptional analysis revealed opposing profiles between genetic models, with genes associated with steroid metabolism and prostaglandin action in db/db mice and genes controlling extracellular matrix in ob/ob mice being downregulated, despite both processes being crucial for follicular development and ovulation. Conclusions: Leptin signalling regulated NLRP3 inflammasome activation and expression of M1 markers in ovaries of obese mice, in an ObRb-dependent and -independent manner. Absence of changes in the expression of leptin signalling and proinflammatory mediators in GCs from db/db and ob/ob mice was associated with impaired folliculogenesis.
2024-04-10 | GSE236196 | GEO
Project description:Obesity leads to ovarian dysfunction and the establishment of local leptin resistance. The aim of our study was to characterise levels of Nod-Like Receptor Protein 3 (NLRP3) inflammasome activation during obesity progression in the mouse ovaries and liver and test the putative role of leptin on its regulation. C57BL/6J mice were treated with equine chorionic gonadotropin (eCG) or human chorionic gonadotropin (hCG) for oestrous cycle synchronisation and ovaries collection. In diet-induced obesity (DIO) model, mice were fed chow diet (CD) or high fat diet (HFD) for 4 or 16 weeks (wk), whereas in hyperleptinemic model (LEPT), mice were injected with leptin for 16 days (16L) or saline (16C) and in the genetic obese leptin-deficient ob/ob (+/? and -/-) animals were fed CD for 4wk. Either ovaries and liver were collected, as well as cumulus cells (CCs) after superovulation from DIO and LEPT. In DIO protocol, protein expression of NLRP3 inflammasome components was increased in 4wk HFD, but decreased in 16wk HFD. Moreover LEPT and ob/ob models revealed NLRP3 and IL-1 upregulation in 16L and downregulation in ob/ob. Transcriptome analysis of CC showed common genes between LEPT and 4wk HFD modulating NLRP3 inflammasome. Moreover analysis in the liver showed upregulation of NLRP3 protein only after 16wk HFD, but also the downregulation of NLRP3 protein in ob/ob-/-. We showed the link between leptin signalling and NLRP3 inflammasome activation in the ovary throughout obesity progression in mice, elucidating the molecular mechanisms underpinning ovarian failure in maternal obesity.
2021-11-01 | GSE180300 | GEO
Project description:Comparison of gene expression in pancreatic islets of BTBR-ob/ob mouse model of obesity-induced type 2 diabetes, and in non-diabetic control mice, B6-ob/ob identified Asf1b as an important gene candidate predictive of diabetic outcome. Asf1B expression was suppressed in response to age in both B6 and BTBR islets, induced by obesity only in B6 islets. This is consistent with other studies reporting a decline in -cell proliferation with age. Asf1b also strongly correlated (R ~ 0.98) with cellular proliferation marker Mki67. Overexpression of Asf1B induced β-cell proliferation in human islets. We show that many genes involved in regulation of cell cycle or programmed cell death are differentially regulated by Asf1B overexpression.
2016-09-10 | GSE86611 | GEO