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Lactobacillus casei Zhang exerts anti-obesity effect to obese glut1 and gut-specific-glut1 knockout mice via gut microbiota modulation mediated different metagenomic pathways

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Abstract

Purpose

Obesity is a major risk factor for various metabolic diseases, including metabolic syndrome and type-2 diabetes. Glucose transporter 1 (GLUT1) impairment has been proposed as a mechanism of fat accumulation and glucose tolerance. Our aims were to determine the role of intestinal epithelial glut1 activity in obesity and the mechanism of anti-obesity effect of Lactobacillus casei Zhang (LCZ) intervention in the absence of gut villi-specific glut1 expression.

Methods

This study compared the body weight, intestinal microbiota perturbations, fat mass accumulation, and glucose tolerance (by oral glucose tolerance test) between high-fat diet fed villi-specific glut1 knockout (KO) mice and control mice (glut1 flox/flox) with/without LCZ intervention. The intestinal microbiota was evaluated by metagenomic sequencing.

Results

Our results showed that villi-specific glut1 KO mice had more fat deposition at the premetaphase stage, impaired glucose tolerance, and obvious alterations in gut microbiota compared to control mice. Probiotic administration significantly lowered the body weight, the weights of mesenteric and perirenal white adipose tissues (WAT), and mediated gut microbiota modulation in both types of KO and control mice. The species Barnesiella intestinihominis and Faecalibaculum rodentium might contribute to fasting fat mass accumulation associated with gut-specific glut1 inactivation, while the probiotic-mediated anti-obesity effect was linked to members of the Bacteroides genera, Odoribacter genera and Alistipes finegoldii.

Conclusion

Our study demonstrated that abrogating gut epithelial GLUT1 activity affected the gut microbiota, fat mass accumulation, and glucose tolerance; and LCZ administration reduced fat mass accumulation and central obesity.

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Acknowledgements

Financial support for this research was provided by the National Natural Science Foundation of China (31720103911, 31972083 and 32001711) and China Agriculture Research System of MOF and MARA.

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Author notes

  1. Qiuwen He and Yong Zhang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China

    Qiuwen He, Da Ma, Weiqin Zhang & Heping Zhang

  2. Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China

    Qiuwen He, Da Ma, Weiqin Zhang & Heping Zhang

  3. School of Chemistry and Biological Engineering, University of Science and Technology Beijing (USTB), Beijing, China

    Yong Zhang

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  1. Qiuwen He
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Correspondence to Heping Zhang.

Supplementary Information

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394_2021_2764_MOESM1_ESM.pdf

Supplemental Figure 1 A. Initial body weight of 8-week-old glut1 fl/fl mice (n=20) and glut1 CKO mice (n=11). p<0.001***. B and C. Genotyping of glut1 fl/fl mice (420bp), heterozygous cre+ mice (420bp,204bp),heterozygous cre- mice (420bp) and glut1 CKO mice (none). (PDF 101 KB)

394_2021_2764_MOESM2_ESM.tif

Supplemental Figure 2. LCZ regulated gut microbiota in HFD-fed wild-type mice and villi-specific glut1 KO mice. (A) Genus-level gut microbiota profiles in different groups, including GV(n = 6), GVP(n = 5), GF(n = 6), GFP (n = 6) and GFT (n = 6). Relative abundances of differential abundant genera in 5 groups: (B) Bacteroides, (C) Alistipes, (D) Ruminococcus, and (E) Barnesiella. p<0.05*; p<0.01**. (TIF 1116 KB)

394_2021_2764_MOESM3_ESM.tif

Supplemental Figure 3. LCZ regulated gut microbiota at species-level in HFD-fed wild-type mice and glut1 CKO mice. Relative abundances of differential abundant species in 5 groups: (A) Bacteroides acidifaciens, (B) Bacteroides intestinalis, (C) Bacteroides rodentium, (D) Bacteroides uniformis, (E) Barnesiella intestinihominis,(F) Alistipes finegoldii, (G) Acetatifactor muris, and (H) Ruminococcus gnavus. p<0.05*; p<0.01**. (TIF 1022 KB)

Supplemental Table 1. Statistics of Spearman’s correlation analysis between groups. (XLSX 27 KB)

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He, Q., Zhang, Y., Ma, D. et al. Lactobacillus casei Zhang exerts anti-obesity effect to obese glut1 and gut-specific-glut1 knockout mice via gut microbiota modulation mediated different metagenomic pathways. Eur J Nutr 61, 2003–2014 (2022). https://doi.org/10.1007/s00394-021-02764-0

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