Hematopoietic tissue factor-protease-activated receptor 2 signaling promotes hepatic inflammation and contributes to pathways of gluconeogenesis and steatosis in obese mice.

ABSTRACT: Failure to inhibit hepatic gluconeogenesis is a major mechanism contributing to fasting hyperglycemia in type 2 diabetes and, along with steatosis, is the hallmark of hepatic insulin resistance. Obesity is associated with chronic inflammation in multiple tissues, and hepatic inflammation is mechanistically linked to both steatosis and hepatic insulin resistance. Here, we delineate a role for coagulation signaling via tissue factor (TF) and proteinase-activated receptor 2 (PAR2) in obesity-mediated hepatic inflammation, steatosis, and gluconeogenesis. In diet-induced obese mice, TF tail signaling independent of PAR2 drives CD11b(+)CD11c(+) hepatic macrophage recruitment, and TF-PAR2 signaling contributes to the accumulation of hepatic CD8(+) T cells. Transcripts of key pathways of gluconeog

SUBMITTER: Wang J 

PROVIDER: S-EPMC4305186 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature