The kielin/chordin-like protein KCP attenuates nonalcoholic fatty liver disease in mice

In this report, we show that aging KCP mutant (Kcp–/–) mice are increasingly susceptible to developing hepatic steatosis and liver fibrosis. When young mice are put on a high-fat diet, Kcp–/– mice are also more susceptible to developing liver pathology, compared with their wild-type littermates. Furthermore, mice that express a Pepck-KCP transgene (KcpTg) in the liver are resistant to developing liver pathology even when fed a high-fat diet. Analyses of liver tissues reveal a significant reduction of P-Smad3, consistent with a role for KCP in suppressing TGF-β signaling. Transcriptome analyses show that livers from Kcp–/– mice fed a normal diet are more like wild-type livers from mice fed a high-fat diet. However, the KCP transgene can suppress many of the changes in liver gene expression that are due to a high-fat diet. These data demonstrate that shifting the TGF-β signaling paradigm with the secreted regulatory protein KCP can significantly alter the liver pathology in aging mice and in diet-induced NAFLD.

Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Soofi, A., Wolf, K. I., Ranghini, E. J., Amin, M. A., Dressler, G. R. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research