Dataset Information

Intestinal α1-2-Fucosylation Contributes to Obesity and Steatohepatitis in Mice.

ABSTRACT:

Background & aims

Fucosyltransferase 2 (Fut2)-mediated intestinal α1- 2-fucosylation is important for host-microbe interactions and has been associated with several diseases, but its role in obesity and hepatic steatohepatitis is not known. The aim of this study was to investigate the role of Fut2 in a Western-style diet-induced mouse model of obesity and steatohepatitis.

Methods

Wild-type (WT) and Fut2-deficient littermate mice were used and features of the metabolic syndrome and steatohepatitis were assessed after 20 weeks of Western diet feeding.

Results

Intestinal α1-2-fucosylation was suppressed in WT mice after Western diet feeding, and supplementation of α1-2-fucosylated glycans exacerbated obesity and steatohepatitis in these mice. Fut2-deficient mice were protected from Western diet-induced features of obesity and steatohepatitis despite an increased caloric intake. These mice have increased energy expenditure and thermogenesis, as evidenced by a higher core body temperature. Protection from obesity and steatohepatitis associated with Fut2 deficiency is transmissible to WT mice via microbiota exchange; phenotypic differences between Western diet-fed WT and Fut2-deficient mice were reduced with antibiotic treatment. Fut2 deficiency attenuated diet-induced bile acid accumulation by altered relative abundance of bacterial enzyme 7-α-hydroxysteroid dehydrogenases metabolizing bile acids and by increased fecal excretion of secondary bile acids. This also was associated with increased intestinal farnesoid X receptor/fibroblast growth factor 15 signaling, which inhibits hepatic synthesis of bile acids. Dietary supplementation of α1-2-fucosylated glycans abrogates the protective effects of Fut2 deficiency.

Conclusions

α1-2-fucosylation is an important host-derived regulator of intestinal microbiota and plays an important role for the pathogenesis of obesity and steatohepatitis in mice.

SUBMITTER: Zhou R

PROVIDER: S-EPMC8166943 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Intestinal α1-2-Fucosylation Contributes to Obesity and Steatohepatitis in Mice.

Zhou Rongrong R Llorente Cristina C Cao Jinling J Zaramela Livia S LS Zeng Suling S Gao Bei B Li Shang-Zhen SZ Welch Ryan D RD Huang Feng-Qing FQ Qi Lian-Wen LW Pan Chuyue C Huang Yan Y Zhou Pengchen P Beussen Iris I Zhang Ying Y Bryam Gregory G Fiehn Oliver O Wang Lirui L Liu E-Hu EH Yu Ruth T RT Downes Michael M Evans Ronald M RM Goglin Karrie K Fouts Derrick E DE Brenner David A DA Bode Lars L Fan Xuegong X Zengler Karsten K Schnabl Bernd B

Cellular and molecular gastroenterology and hepatology 20210222 1

<h4>Background & aims</h4>Fucosyltransferase 2 (Fut2)-mediated intestinal α1- 2-fucosylation is important for host-microbe interactions and has been associated with several diseases, but its role in obesity and hepatic steatohepatitis is not known. The aim of this study was to investigate the role of Fut2 in a Western-style diet-induced mouse model of obesity and steatohepatitis.<h4>Methods</h4>Wild-type (WT) and Fut2-deficient littermate mice were used and features of the metabolic syndrome and ...[more]

PMID: 33631374

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Dataset Information

Intestinal α1-2-Fucosylation Contributes to Obesity and Steatohepatitis in Mice.

Background & aims

Methods

Results

Conclusions

Publications

Intestinal α1-2-Fucosylation Contributes to Obesity and Steatohepatitis in Mice.

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