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 -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 amyloid aggregates. This is associated with increased basal insulin signaling and decreased insulin-stimulated signaling. Moreover, MME differentially regulates the internalization and turnover of the / 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. SOURCE: Alfred Ramirez (alfred.ramirez@joslin.harvard.edu) -  Joslin Diabetes Center

Pluto Bioinformatics

GSE117270: Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes (RNA-Seq)