Hepatology international · 2022
Colesevelam ameliorates non-alcoholic steatohepatitis and obesity in mice.
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Hartmann Phillipp, Duan Yi, Miyamoto Yukiko, Demir Münevver, Lang Sonja, Hasa Elda, Stern Patrick, Yamashita Dennis, Conrad Mary, Eckmann Lars, Schnabl Bernd
Аннотация
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.
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.