Membrane metallo-endopeptidase (Neprilysin) regulates inflammatory response and insulin signaling in white preadipocytes

Molecular Metabolism
Alfred K RamirezC Ronald Kahn

Abstract

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. We 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. MME 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 increa...Continue Reading

Citations

Feb 6, 2020·International Journal of Molecular Sciences·Elisa WeißUrsula Hiden
May 1, 2021·International Journal of Molecular Sciences·Jan FrohlichManlio Vinciguerra

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Datasets Mentioned

BETA
GSE117353

Methods Mentioned

BETA
PCR
HT-seq
FACS
pulldown
immunoprecipitation
RNA-seq
RNA seq
transfection
glycosylation

Software Mentioned

HTSeq
ggplot2
Spliced Transcripts to Alignment Reference ( STAR
HT
seq
Gene Set Enrichment Analysis ( GSEA )
DESeq2
EBimage
DEXSeq
R

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