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Status |
Public on Feb 25, 2019 |
Title |
Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes (RNA-Seq) |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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.
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Overall design |
RNA-seq of preadipocytes derived from the abomindal subcutaneous, omental, and mesenteric adipose tissue depot
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Contributor(s) |
Ramirez AK, Dankel S, Cai W, Sakaguchi M, Kasif S, Kahn CR |
Citation(s) |
30795914 |
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Submission date |
Jul 17, 2018 |
Last update date |
Mar 27, 2019 |
Contact name |
Alfred Ramirez |
E-mail(s) |
alfred.ramirez@joslin.harvard.edu
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Organization name |
Joslin Diabetes Center
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Street address |
One Joslin Place
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02215 |
Country |
USA |
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Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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Samples (11)
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This SubSeries is part of SuperSeries: |
GSE117353 |
Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes |
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Relations |
BioProject |
PRJNA481672 |
SRA |
SRP154309 |