Preventing simultaneous activation of counteracting metabolic pathways
Density-enhanced phosphatase 1 (DEP-1) negatively modulates the insulin receptor (IR) in peripheral tissues. This study shows that DEP-1 is an insulin-regulated gene, dysregulated in obesity.
The researchers highlight DEP-1 as a key neuronal IR phosphatase that prevents concurrent activation of anabolic and catabolic pathways.
The authors show that in DEP-1 forebrain specific KO mice, simultaneous insulin (anabolic) and AMPK (catabolic) signaling results in increased lipolysis in WAT and altered BAT activity due to enhanced sympathetic activation.
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01335-4
