Universität zu Köln

Hartmann, Phillipp, Duan, Yi, Miyamoto, Yukiko, Demir, Munevver ORCID: 0000-0002-7050-797X, Lang, Sonja, Hasa, Elda, Stern, Patrick, Yamashita, Dennis, Conrad, Mary, Eckmann, Lars and Schnabl, Bernd (2022). Colesevelam ameliorates non-alcoholic steatohepatitis and obesity in mice. Hepatol. Int., 16 (2). S. 359 - 371. NEW YORK: SPRINGER. ISSN 1936-0541

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Abstract

Background Obesity, non-alcoholic fatty liver disease (NAFLD) and its more advanced form non-alcoholic steatohepatitis (NASH) are important causes of morbidity and mortality worldwide. Bile acid dysregulation is a pivotal part in their pathogenesis. The aim of this study was to evaluate the bile acid sequestrant colesevelam in a microbiome-humanized mouse model of diet-induced obesity and steatohepatitis. Methods Germ-free C57BL/6 mice were associated with stool from patients with NASH and subjected to 20 weeks of Western diet feeding with and without colesevelam. Results Colesevelam reduced Western diet-induced body and liver weight gain in microbiome-humanized mice compared with controls. It ameliorated Western diet-induced hepatic inflammation, steatosis, fibrosis and insulin resistance. Colesevelam increased de novo bile acid synthesis and decreased hepatic cholesterol content in microbiome-humanized mice fed a Western diet. It further induced the gene expression of the antimicrobials Reg3g and Reg3b in the distal small intestine and decreased plasma levels of LPS. Conclusions Colesevelam ameliorates Western diet-induced steatohepatitis and obesity in microbiome-humanized mice.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hartmann, Phillipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Duan, Yi UNSPECIFIED UNSPECIFIED UNSPECIFIED Miyamoto, Yukiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Demir, Munevver UNSPECIFIED orcid.org/0000-0002-7050-797X UNSPECIFIED Lang, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Hasa, Elda UNSPECIFIED UNSPECIFIED UNSPECIFIED Stern, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Yamashita, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED Conrad, Mary UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckmann, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Schnabl, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-687087
DOI:	10.1007/s12072-022-10296-w
Journal or Publication Title:	Hepatol. Int.
Volume:	16
Number:	2
Page Range:	S. 359 - 371
Date:	2022
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1936-0541
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FATTY LIVER-DISEASE; HEPATIC STEATOSIS; GLYCEMIC CONTROL; DOUBLE-BLIND; MODEL Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68708