Colesevelam Reduces Ethanol-Induced Liver Steatosis in Humanized Gnotobiotic Mice

被引：10

作者：

Cabre, Noemi ^{[1
]}

Duan, Yi ^{[1
]}

Llorente, Cristina ^{[1
]}

Conrad, Mary ^{[2
]}

Stern, Patrick ^{[2
]}

Yamashita, Dennis ^{[2
,4
]}

Schnabl, Bernd ^{[1
,3
]}

机构：

[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[2] Axial Therapeut, Woburn, MA 01801 USA

[3] VA San Diego Healthcare Syst, Dept Med, San Diego, CA 92161 USA

[4] Cambrian Biopharma, Brooklyn, NY 10003 USA

来源：

CELLS | 2021年 / 10卷 / 06期

关键词：

alcoholic liver disease; bile acids; microbiome; ALCOHOLIC HEPATITIS; BILE-ACID; GLYCEMIC CONTROL; DOUBLE-BLIND; LONG-TERM; DISEASE;

D O I：

10.3390/cells10061496

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Alcohol-related liver disease is associated with intestinal dysbiosis. Functional changes in the microbiota affect bile acid metabolism and result in elevated serum bile acids in patients with alcohol-related liver disease. The aim of this study was to identify the potential role of the bile acid sequestrant colesevelam in a humanized mouse model of ethanol-induced liver disease. We colonized germ-free (GF) C57BL/6 mice with feces from patients with alcoholic hepatitis and subjected humanized mice to the chronic-binge ethanol feeding model. Ethanol-fed gnotobiotic mice treated with colesevelam showed reduced hepatic levels of triglycerides and cholesterol, but liver injury and inflammation were not decreased as compared with non-treated mice. Colesevelam reduced hepatic cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1) protein expression, although serum bile acids were not lowered. In conclusion, our findings indicate that colesevelam treatment mitigates ethanol-induced liver steatosis in mice.

引用

页数：11

共 33 条

[1] Alcohol Abstinence in Patients Surviving an Episode of Alcoholic Hepatitis: Prediction and Impact on Long-Term Survival [J].

Altamirano, Jose ;

Lopez-Pelayo, Hugo ;

Michelena, Javier ;

Jones, Patricia D. ;

Ortega, Lluisa ;

Gines, Pere ;

Caballeria, Juan ;

Gual, Antoni ;

Bataller, Ramon ;

Lligona, Anna .

HEPATOLOGY, 2017, 66 (06) :1842-1853

[2] Goal achievement ofHbA1candLDL-cholesterol in a randomized trial comparing colesevelam with ezetimibe:GOAL-RCT [J].

Bajaj, Harpreet S. ;

Brown, Ruth E. ;

Jiandani, Dishay ;

Venn, Karri ;

Al-Asaad, Hani ;

Khandwala, Hasnain ;

Steen, Oren ;

Abdel-Salam, Suzan ;

Aronson, Ronnie .

DIABETES OBESITY & METABOLISM, 2020, 22 (10) :1722-1728

[3] Colesevelam for the treatment of bile acid malabsorption-associated diarrhea in patients with Crohn's disease: A randomized, double-blind, placebo-controlled study [J].

Beigel, Florian ;

Teich, Niels ;

Howaldt, Stefanie ;

Lammert, Frank ;

Maul, Jochen ;

Breiteneicher, Simone ;

Rust, Christian ;

Goeke, Burkhard ;

Brand, Stephan ;

Ochsenkuehn, Thomas .

JOURNAL OF CROHNS & COLITIS, 2014, 8 (11) :1471-1479

[4] Mouse model of chronic and binge ethanol feeding (the NIAAA model) [J].

Bertola, Adeline ;

Mathews, Stephanie ;

Ki, Sung Hwan ;

Wang, Hua ;

Gao, Bin .

NATURE PROTOCOLS, 2013, 8 (03) :627-637

[5] The Effect of Colesevelam Treatment on Bile Acid and Lipid Metabolism and Glycemic Control in Healthy Men [J].

Blahova, T. ;

Peterkova, L. ;

Lenicek, M. ;

Vlachova, M. ;

Zemankova, K. ;

Adamkova, V. ;

Vitek, L. ;

Kovar, J. .

PHYSIOLOGICAL RESEARCH, 2016, 65 (06) :995-1003

[6]

Brandl K, 2018, J HEPATOL, V69, P396, DOI 10.1016/j.jhep.2018.03.031

[7] Improved Glycemic Control with Colesevelam Treatment in Patients with Type 2 Diabetes Is Not Directly Associated with Changes in Bile Acid Metabolism [J].

Brufau, Gemma ;

Stellaard, Frans ;

Prado, Kris ;

Bloks, Vincent W. ;

Jonkers, Elles ;

Boverhof, Renze ;

Kuipers, Folkert ;

Murphy, Elizabeth J. .

HEPATOLOGY, 2010, 52 (04) :1455-1464

[8] Spectrum of Alcoholic Liver Disease [J].

Chacko, Kristina Rachel ;

Reinus, John .

CLINICS IN LIVER DISEASE, 2016, 20 (03) :419-+

[9] Microbiota Protects Mice Against Acute Alcohol-Induced Liver Injury [J].

Chen, Peng ;

Miyamoto, Yukiko ;

Mazagova, Magdalena ;

Lee, Kuei-Chuan ;

Eckmann, Lars ;

Schnabl, Bernd .

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2015, 39 (12) :2313-2323

[10] Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia [J].

Crabb, David W. ;

Bataller, Ramon ;

Chalasani, Naga P. ;

Kamath, Patrick S. ;

Lucey, Michael ;

Mathurin, Philippe ;

McClain, Craig ;

McCullough, Arthur ;

Mitchell, Mack C. ;

Morgan, Timothy R. ;

Nagy, Laura ;

Radaeva, Svetlana ;

Sanyal, Arun ;

Shah, Vijay ;

Szabo, Gyongyi .

GASTROENTEROLOGY, 2016, 150 (04) :785-790

← 1 2 3 4 →