Notum promotes thermogenesis and protects against diet-induced obesity and insulin resistance in mice

Notum is a liver-secreted inhibitor of Wnt signaling pathway, which protected against diet induced obesity and improved glucose homeostasis when overexpressed in the mouse liver. Adeno-associated virus (AAV) vectors were used to overexpress green fluorescent protein (GFP) or Notum in the livers of male C57BL/6J mice maintained on a chow diet. Four weeks after the AAV injection, inguinal white adipose tissue (WAT) of these mice were collected to study Notum’s effect on gene expression. RNA-seq analysis of inguinal WAT collected from these mice revealed a highly significant enrichment of extracellular matrix (ECM) gene set among the down-regulated genes in the AAV-Notum group as compared to the AAV-GFP group. These data suggest that Notum inhibits WAT fibrosis, which may be one of the mechanisms by which Notum improves glucose homeostasis. Eight week old male C57BL6/J mice were each injected through the tail vein 1x10^12 genome copies of adeno associated viruses that overexpress either GFP or Notum in a liver specific fashion. After 4 weeks of chow diet feeding, the mice were fasted for 4 hours, euthanized for the collection of inguinal WAT for RNA-seq experiment.