Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Feb;17(1):64-75.
doi: 10.1016/j.gpb.2019.03.001. Epub 2019 Apr 23.

Inulin Can Alleviate Metabolism Disorders in ob/ob Mice by Partially Restoring Leptin-related Pathways Mediated by Gut Microbiota

Xiaofeng Song  1 , Liang Zhong  2 , Na Lyu  3 , Fei Liu  3 , Boxing Li  2 , Yanan Hao  2 , Yong Xue  4 , Jing Li  3 , Yuqing Feng  5 , Yue Ma  5 , Yongfei Hu  6 , Baoli Zhu  7
Affiliations

Inulin Can Alleviate Metabolism Disorders in ob/ob Mice by Partially Restoring Leptin-related Pathways Mediated by Gut Microbiota

Xiaofeng Song et al. Genomics Proteomics Bioinformatics. 2019 Feb.

Abstract

Inulin has been used as a prebiotic to alleviate glucose and lipid metabolism disorders in mice and humans by modulating the gut microbiota. However, the mechanism underlying the alleviation of metabolic disorders by inulin through interactions between the gut microbiota and host cells is unclear. We use ob/ob mice as a model to study the effect of inulin on the cecal microbiota by 16S rRNA gene amplicon sequencing and its interaction with host cells by transcriptomics. The inulin-supplemented diet improved glucose and lipid metabolism disorder parameters in ob/ob mice, alleviating fat accumulation and glucose intolerance. The α diversity of gut microbial community of ob/ob mice was reduced after inulin treatment, while the β diversity tended to return to the level of wild type mice. Interestingly, Prevotellaceae UCG 001 (family Prevotellaceae) was obviously enriched after inulin treatment. A comparative analysis of the gene expression profile showed that the cecal transcriptome was changed in leptin gene deficiency mice, whereas the inulin-supplemented diet partially reversed the changes in leptin gene-related signaling pathways, especially AMPK signaling pathway, where the levels of gene expression became comparable to those in wild type mice. Further analysis indicated that Prevotellaceae UCG 001 was positively correlated with the AMPK signaling pathway, which was negatively correlated with markers of glycolipid metabolism disorders. Our results suggest that the inulin-supplemented diet alleviates glucose and lipid metabolism disorders by partially restoring leptin related pathways mediated by gut microbiota.

Keywords: Gut microbiota; Metabolic disorders; Obesity; Prebiotics; Transcriptome.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Improvement in metabolic parameters in ob/ob mice by inulin A. Daily food intake. B. Liver index. C. Serum TC. D. Ratio of TC/HDL-C. E. Plasma glucose (mM) profile. *P < 0.05 for ob/ob inulin versus wild type; $P < 0.05 for ob/ob inulin versus ob/ob. F. Mean AUC measured during the IPGTT mM·min). G. Relative expression of colonic Glp-1. H. Representative H&E-stained images of the liver. Scale bars, 200 μm. n = 6 per group. TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; AUC, area under the curve; IPGTT, intraperitoneal glucose tolerance test; Glp-1, glucagon-like peptide-1. Data are presented as mean ± SEM. Data were analyzed using one-way ANOVA followed by the Tukey post hoc test for A–D, F, and G and with two-way ANOVA followed by the Bonferroni post hoc test for E. n = 6 per group. **P < 0.01; ***P < 0.001.
Figure 2
Figure 2
Inulin modifies the composition of the cecal microbiota in ob/ob mice A. OTU number. B. Shannon index of microbiota. C. Simpson index of microbiota. D.. LDA scores of differentially abundant taxa between the wild type and ob/ob mice using the LEfSe method. E. LDA scores of differentially abundant taxa between the ob/ob and ob/ob inulin mice using the LEfSe method. F. Relative abundance of Prevotellaceae UCG 001. G. Relative abundance of Alistipes, Anaerotruncus, Intestinimonas, and Family XIII UCG 001. OTU, operational taxonomic unit. Data were analyzed using one-way ANOVA followed by the Tukey post hoc test for A–C, and Kruskal–Wallis sum-rank test and Wilcoxon rank-sum test for D, E. n = 6 per group. *P < 0.05.
Figure 3
Figure 3
Transcriptomic analyses of the cecal tissue A. Heatmap of the expression values of 8 signaling pathways in each sample. The expression values of 18 samples are presented as the normalized z-score using the enrichment score of signaling pathways. B. Enrichment score of 8 signaling pathways. Data were analyzed using one-way ANOVA followed by the Tukey post hoc test for B.n = 6 per group. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 4
Figure 4
Correlations among gut bacteria, signaling pathways, and metabolic parameters A. Heatmap of the Spearman correlations between 5 genera, 8 signaling pathways and 5 metabolic parameters. B. Heatmap of the Spearman correlations between 5 genera and 8 signaling pathways. TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; AUC, area under the curve; IPGTT, intraperitoneal glucose tolerance test. n = 6 per group. *P < 0.05.
Figure 5
Figure 5
Presumed mechanism by which inulin alleviated glucose and lipid metabolism disorders in ob/ob mice The inulin-supplemented diet promotes the proliferation of Prevotellaceae UCG 001 in the gut of ob/ob mice. This strain degrades inulin to produce SCFAs, which recognized GPR41/43 on the surface of intestinal epithelial cells, and lead to activation of the AMPK signaling pathway. Finally, this signal leads to changes in downstream metabolic functions. SCFAs, short-chain fatty acids; GPR41/43, G protein-coupled receptors 41/43; AMPK, adenosine monophosphate (AMP)-activated protein kinase; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; AUC, area under the curve; IPGTT, intraperitoneal glucose tolerance test.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bindels L.B., Delzenne N.M., Cani P.D., Walter J. Towards a more comprehensive concept for prebiotics. Nat Rev Gastroenterol Hepatol. 2015;12:303–310. - PubMed
    1. Niness K.R. Inulin and oligofructose: what are they? J Nutr. 1999;129:1402–1406. - PubMed
    1. Everard A., Lazarevic V., Derrien M., Girard M., Muccioli G.G., Neyrinck A.M. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes. 2011;60:2775–2786. - PMC - PubMed
    1. Zhao L., Zhang F., Ding X., Wu G., Lam Y.Y., Wang X. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359:1151–1156. - PubMed
    1. Catry E., Bindels L.B., Tailleux A., Lestavel S., Neyrinck A.M., Goossens J.F. Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction. Gut. 2018;67:271–283. - PMC - PubMed

Publication types