絞り込み

17082

広告

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.

著者 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
Am J Pathol.2017 Dec 14 ; ():.
この記事をPubMed上で見るPubMedで表示
この記事をGoogle翻訳上で見る Google翻訳で開く

スターを付ける スターを付ける     (3view , 0users)

Full Text Sources

Medical

Miscellaneous

Molecular Biology Databases

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 mice had increased intrahepatic biliary mass, biliary proliferation and senescence, fibrosis, and hepatic stellate cell activation, which were reduced in Hdc-/- HFD mice. In Hdc-/- HFD mice, serum leptin levels increased, whereas biliary Ob-R expression decreased. NASH patients had increased HDC/histamine/histamine receptor signaling. Hdc-/- HFD mice are susceptible to obesity via dysregulated leptin/Ob-R signaling, whereas the lack of HDC protects from HFD-induced fibrosis and cholangiocyte damage. HDC/histamine/leptin signaling may be important in managing obesity-induced biliary damage.
PMID: 29248461 [PubMed - as supplied by publisher]
印刷用ページを開く Endnote用テキストダウンロード