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: Devram S. Ghorpade Lale Ozcan Ze Zheng Sarah M. Nicoloro Yuefei Shen Emily Chen Matthias Bl üher Michael P. Czech Ira Tabas Tags: Letter Source Type: research
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