Knockout of l-Histidine Decarboxylase (HDC-/-) Prevents Cholangiocyte Damage and Hepatic Fibrosis in Mice Subjected to High-Fat Diet Feeding via Disrupted Histamine/Leptin Signaling.

Knockout of l-Histidine Decarboxylase (HDC-/-) Prevents Cholangiocyte Damage and Hepatic Fibrosis in Mice Subjected to High-Fat Diet Feeding via Disrupted Histamine/Leptin Signaling.
Am J Pathol. 2017 Dec 14;:
Authors: Kennedy L, Hargrove L, Demieville J, Bailey J, Dar W, Polireddy K, Chen Q, Nevah Rubin MI, Sybenga A, DeMorrow S, Meng F, Stockton L, Alpini G, Francis H
Abstract
Administration of a high-fat diet (HFD) coupled with sugar, mimicking a Western diet, causes fatty liver disease in mice. Histamine induces biliary proliferation and fibrosis, and regulates leptin signaling. Wild-type (WT) and l-histidine decarboxylase (Hdc-/-) mice were fed a control diet or a HFD coupled with a high fructose corn syrup equivalent. H&E and Oil Red O staining were performed to determine steatosis. Intrahepatic biliary mass and cholangiocyte proliferation were evaluated by immunohistochemistry. Senescence and fibrosis were measured by qPCR and immunohistochemistry. Hepatic stellate cell activation was detected by immunofluorescence. Histamine and leptin levels were measured by EIA. The leptin receptor, Ob-R, was evaluated by qPCR in cholangiocytes lacking HDC. The HDC/histamine/histamine receptor axis, ductular reaction, and biliary senescence were evaluated in patients with non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or end-stage liver disease. Hdc-/- HFD mice had increased steatosis compared to WT HFD mice. WT HFD m...

Source: The American Journal of Pathology - December 14, 2017 Category: Pathology Authors: Kennedy L, Hargrove L, Demieville J, Bailey J, Dar W, Polireddy K, Chen Q, Nevah Rubin MI, Sybenga A, DeMorrow S, Meng F, Stockton L, Alpini G, Francis H Tags: Am J Pathol Source Type: research