Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance

Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance Nature 555, 7698 (2018). doi:10.1038/nature26138 Authors: Devram S. Ghorpade, Lale Ozcan, Ze Zheng, Sarah M. Nicoloro, Yuefei Shen, Emily Chen, Matthias Blüher, Michael P. Czech & Ira Tabas Obesity-induced metabolic disease involves functional integration among several organs via circulating factors, but little is known about crosstalk between liver and visceral adipose tissue (VAT). In obesity, VAT becomes populated with inflammatory adipose tissue macrophages (ATMs). In obese humans, there is a close correlation between adipose tissue inflammation and insulin resistance, and in obese mice, blocking systemic or ATM inflammation improves insulin sensitivity. However, processes that promote pathological adipose tissue inflammation in obesity are incompletely understood. Here we show that obesity in mice stimulates hepatocytes to synthesize and secrete dipeptidyl peptidase 4 (DPP4), which acts with plasma factor Xa to inflame ATMs. Silencing expression of DPP4 in hepatocytes suppresses inflammation of VAT and insulin resistance; however, a similar effect is not seen with the orally administered DPP4 inhibitor sitagliptin. Inflammation and insulin resistance are also suppressed by silencing expression of caveolin-1 or PAR2 in ATMs; these prot...
Source: Nature - Category: Research Authors: Tags: Letter Source Type: research