Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes (Microarray Expression)
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PROVIDER: PRJNA481870 | ENA |
REPOSITORIES: ENA
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Project description:Accumulation of subcutaneous white adipose tissue (WAT) is associated with increased insulin sensitivity, low levels of inflammation and a generally metabolically-healthy state, whereas accumulation of visceral adipose tissue is associated with insulin resistance, adipose tissue inflammation and metabolic syndrome. Membrane Metallo-Endopeptidase (MME/Neprislyin) is an extracellular, membrane-bound protease enriched in subcutaneous WAT that can target degradation of a variety of peptides, including insulin, IL6, and β-amyloids. Here, we show that MME in white preadipocytes is differently expressed in subcutaneous vs visceral WAT, and favors insulin signaling and a low inflammatory response. Thus, knockdown of MME in preadipocytes increases the inflammatory response to substance P and amyloidβ aggregates. This is associated with increased basal insulin signaling and decreased insulin-stimulated signaling. Moreover, MME differentially regulates the internalization and turnover of the α/β subunits of the insulin receptor. Thus, MME is a novel regulator of the insulin receptor in adipose tissue and may serve as a therapeutic target to increase insulin sensitivity and decrease inflammatory susceptibility.
2019-02-25 | GSE117352 | GEO
Project description:Accumulation of subcutaneous white adipose tissue (WAT) is associated with increased insulin sensitivity, low levels of inflammation and a generally metabolically-healthy state, whereas accumulation of visceral adipose tissue is associated with insulin resistance, adipose tissue inflammation and metabolic syndrome. Membrane Metallo-Endopeptidase (MME/Neprislyin) is an extracellular, membrane-bound protease enriched in subcutaneous WAT that can target degradation of a variety of peptides, including insulin, IL6, and β-amyloids. Here, we show that MME in white preadipocytes is differently expressed in subcutaneous vs visceral WAT, and favors insulin signaling and a low inflammatory response. Thus, knockdown of MME in preadipocytes increases the inflammatory response to substance P and amyloidβ aggregates. This is associated with increased basal insulin signaling and decreased insulin-stimulated signaling. Moreover, MME differentially regulates the internalization and turnover of the α/β subunits of the insulin receptor. Thus, MME is a novel regulator of the insulin receptor in adipose tissue and may serve as a therapeutic target to increase insulin sensitivity and decrease inflammatory susceptibility.
2019-02-25 | GSE117270 | GEO
Project description:Accumulation of visceral white adipose tissue (WAT) associates with insulin resistance, adipose tissue inflammation, and metabolic syndrome, whereas accumulation of subcutaneous WAT may be protective. We aimed to identify molecular mechanisms that might provide mechanistic insights underlying the phenotypic differences in these tissues. Membrane Metallo-Endopeptidase (MME/Neprislyin) is an extracellular, membrane-bound protease enriched in subcutaneous WAT that can target degradation of a variety of peptides, including insulin, IL6, and β-amyloids. We hypothesized that MME contributes to adipose depot-specific metabolic properties.
2019-02-25 | GSE117353 | GEO
Project description:Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes
| PRJNA481868 | ENA
Project description:Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes (RNA-Seq)
| PRJNA481672 | ENA
Project description:ObjectiveAccumulation of visceral white adipose tissue (WAT) associates with insulin resistance, adipose tissue inflammation, and metabolic syndrome, whereas accumulation of subcutaneous WAT may be protective. We aimed to identify molecular mechanisms that might provide mechanistic insights underlying the phenotypic differences in these tissues. Membrane Metallo-Endopeptidase (MME/Neprislyin) is an extracellular, membrane-bound protease enriched in subcutaneous WAT that can target degradation of a variety of peptides, including insulin, IL6, and β-amyloids. We hypothesized that MME contributes to adipose depot-specific metabolic properties.MethodsWe performed RNA sequencing on human subcutaneous and visceral preadipocytes and array gene expression profiling in murine subcutaneous and visceral preadipocytes. We conducted several insulin signaling and inflammatory response experiments on different cellular states of MME expression.ResultsMME in white preadipocytes is expressed at a higher level in subcutaneous compared to visceral WAT and favors insulin signaling and a low inflammatory response. Thus, knockdown of MME in subcutaneous preadipocytes increased the inflammatory response to substance P and amyloid β aggregates. This associated with increased basal insulin signaling and decreased insulin-stimulated signaling. Moreover, MME differentially regulates the internalization and turnover of the α/β subunits of the insulin receptor.ConclusionMME is a novel regulator of the insulin receptor in adipose tissue. Given the clinical significance of both chronic inflammation and insulin sensitivity in metabolic disease, these results show a potentially new target to increase insulin sensitivity and decrease inflammatory susceptibility.
| S-EPMC6437599 | biostudies-literature
Project description:Adipogenesis is one of the most intensively studied models of cellular differentiation, and transcriptional activities involved in the process have been extensively investigated. We analyzed transcripts differentially expressed between hen preadipocytes treated with adipogenic cocktail containing 500 nM dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine, 20 µg/mL insulin and 300 μM OA (DMIOA) and non-treated control cells and transcripts differentially expressed between preadipocytes treated with DMIOA alone and those treated with a combination of DMIOA and 20(S)-hydroxycholesterol (DMIOA + 20(S)) using Affymetrix GeneChip® Chicken Genome Array containing 28,000 transcripts. Preadipocytes were isolated from hen abdominal tissue, cultured and treated with DMIOA, DMIOA+Retinoic Acid
2016-05-28 | E-GEOD-81994 | biostudies-arrayexpress
Project description:Obesity is often associated with a low-grade systemic inflammation state that contributes to the development of insulin resistance and atherosclerotic complications. This is usually coupled with increased macrophage infiltration in the adipose tissue and a defect in adipocyte differentiation that results in accumulation of hypertrophic fat cells characterized by a deregulated pattern of adipokine expression. Here we show that knockdown of histone demethylase lsd1 in 3T3-L1 preadipocytes results in defective adipogenesis and derepression of an inflammatory program in these cells. The dataset consists of four sample groups: [1] 3T3-L1 preadipocytes (passage 19) transfected with a control scrambled siRNA at 24h after transfection (siC.24h), [2] 3T3-L1 preadipocytes (p.19) transfected with a siRNA directed against LSD1 at 24h after transfection (siLsd1.24h), [3] 3T3-L1 preadipocytes (p.21) transfected with a control scrambled siRNA at 48h after transfection (siC.48h), and [4] 3T3-L1 preadipocytes (p.21) transfected with a siRNA directed against LSD1 at 48h after transfection (siLsd1.48h). The 24h sample groups (siC.24h and siLsd1.24h) consist of two biological replicate samples; the 48h sample groups (siC.48h and siLsd1.48h) consist of three biological replicate samples. Each sample was hybridized to a separate array, for a total of ten arrays.
2013-12-31 | E-GEOD-25423 | biostudies-arrayexpress
Project description:Adipogenesis is one of the most intensively studied models of cellular differentiation, and transcriptional activities involved in the process have been extensively investigated. We analyzed transcripts differentially expressed between hen preadipocytes treated with adipogenic cocktail containing 500 nM dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine, 20 ug/mL insulin and 300 uM OA (DMIOA) and non-treated control cells and transcripts differentially expressed between preadipocytes treated with DMIOA alone and those treated with a combination of DMIOA and 20(S)-hydroxycholesterol (DMIOA + 20(S)) using Affymetrix GeneChip Chicken Genome Array containing 28,000 transcripts.
2013-09-17 | GSE50880 | GEO
Project description:Insulin resistance and Type 2 Diabetes Mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. To identify the underlying molecular processes in preadipocytes of T2DM patients that are a characteristic of the development of T2DM, preadipocyte cell cultures were prepared from subcutaneous fat biopsies of T2DM patients and compared with age- and BMI matched control subjects. Gene expression profiling showed changed expression of transcription factors involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were down-regulated, and inflammation/apoptosis was up-regulated in T2DM preadipocytes. The down-regulation of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage.
2009-12-31 | GSE15790 | GEO