JOURNAL ARTICLE

Tauroursodeoxycholic acid attenuates progression of steatohepatitis in mice fed a methionine-choline-deficient diet

Eun-Ju Cho, Jung-Hwan Yoon, Min-Sun Kwak, Eun Sun Jang, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim, Chung Yong Kim, Hyo-Suk Lee
Digestive Diseases and Sciences 2014, 59 (7): 1461-74
24865256

BACKGROUND AND AIM: Endoplasmic reticulum (ER) stress has been implicated in the development of nonalcoholic steatohepatitis. A methionine-choline-deficient (MCD) diet induces robust ER stress response and steatohepatitis, but the effects of ER stress modulation on the course of steatohepatitis remain uncertain. The present study evaluated whether reducing ER stress using the chemical chaperone tauroursodeoxycholic acid (TUDCA) could limit hepatocyte lipoapoptosis and progression of MCD diet-induced steatohepatitis.

METHODS: HuH7 cells stably transfected with sodium taurocholate cotransporting polypeptide (HuH-Ntcp cells) and palmitate (PA) were used. Experimental steatohepatitis was induced in male C57BL/6 mice using an MCD diet, and three different doses of TUDCA (500, or 1,000 mg/kg, once daily; or 500 mg/kg twice daily) were administered by gavage from the start of the MCD diet regimen or after 4 weeks.

RESULTS: TUDCA reduced PA-induced ER stress as manifested by decreased eIF2α phosphorylation, XBP1 splicing and expression of BiP, ATF4, and CHOP in HuH-Ntcp cells. TUDCA also decreased PA-induced JNK phosphorylation, Puma up-regulation and Bax activation, which in turn suppressed caspase-dependent hepatocyte lipoapoptosis. Mice given TUDCA did not show a significant decrease in the intrahepatic triglyceride contents and steatosis. However, TUDCA treatment significantly reduced hepatic damage compared to controls for both early and late treatment groups. TUDCA treatment reduced the expression of ER stress markers and pro-apoptotic proteins, leading to decreased apoptosis and oxidative stress. Finally, TUDCA reduced histological fibrosis along with the down-regulation of pro-fibrotic gene expression in both early and late treatment groups.

CONCLUSIONS: These results show that TUDCA attenuates the progression of MCD diet-induced steatohepatitis by reducing ER stress.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
24865256
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"