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Molecular Biology

Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity

International Journal of Obesity volume 45, pages 143–154 (2021)Cite this article

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Abstract

Lipocalin 2 (Lcn2), as an antimicrobial peptide is expressed in intestine, and the upregulation of intestinal Lcn2 has been linked to inflammatory bowel disease. However, the role of Lcn2 in shaping gut microbiota during diet-induced obesity (DIO) remains unknown. We found that short-term high fat diet (HFD) feeding strongly stimulates intestinal Lcn2 expression and secretion into the gut lumen. As the HFD feeding prolongs, fecal Lcn2 levels turn to decrease. Lcn2 deficiency accelerates the development of HFD-induced intestinal inflammation and microbiota dysbiosis. Moreover, Lcn2 deficiency leads to the remodeling of microbiota-derived metabolome, including decreased production of short-chain fatty acids (SCFAs) and SCFA-producing microbes. Most importantly, we have identified Lcn2-targeted bacteria and microbiota-derived metabolites that potentially play roles in DIO and metabolic dysregulation. Correlation analyses suggest that Lcn2-targeted Dubosiella and Angelakisella have a novel role in regulating SCFAs production and obesity. Our results provide a novel mechanism involving Lcn2 as an antimicrobial host factor in the control of gut microbiota symbiosis during DIO.

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Fig. 1: Regulation of Lcn2 expression and secretion in the gut by HFD feeding.
Fig. 2: HFD-induced reshaping of gut microbiota in LKO mice.
Fig. 3: HFD-induced reshaping of gut microbiota in LKO mice.
Fig. 4: Identification of differentially abundant bacteria between WT and LKO mice.
Fig. 5: Remodeling of fecal metabolites in LKO mice during HFD consumption.
Fig. 6: Correlation of body weight with microbes and metabolites.
Fig. 7: Time-dependent effect of HFD on intestinal inflammation in LKO mice.

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Acknowledgements

This work was supported by Allen Foundation Grant awarded to XC, the General Mills Foundation Chair in Genomics for Healthful Foods to XC, NIDDK Grant (R01 DK123042) awarded to XC, and the Doctoral Dissertation Fellowship from the University of Minnesota to XQ.

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Authors and Affiliations

  1. Department of Food Science and Nutrition, University of Minnesota, Twin Cities, MN, 55455, USA

    Xiaoxue Qiu, Yiwei Ma, Hong Guo, Chi Chen & Xiaoli Chen

  2. Clinical Translational Science Institute, University of Minnesota, Twin Cities, MN, 55455, USA

    Marissa G. Macchietto & Steven Shen

  3. Department of Computer Science and Engineering, Graduate Program in Bioinformatics and Computational Biology, University of Minnesota, Twin Cities, MN, 55455, USA

    Xiaotong Liu

  4. Department of Plant and Microbial Biology, Microbial and Plant Genomics Institute, University of Minnesota, Twin Cities, MN, 55455, USA

    You Lu

  5. Department of Animal Science, University of Minnesota, Twin Cities, MN, 55455, USA

    Milena Saqui-Salces

  6. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Twin Cities, MN, 55455, USA

    David A. Bernlohr

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Contributions

XQ designed and performed the experiments, analyzed the data including 16S rRNA sequencing data, and wrote this article. MM analyzed 16S rRNA sequencing data and wrote part of the Methods. XL analyzed 16S rRNA sequencing data. XQ and YL performed statistical analysis. YM and HG performed the experiments. MS performed IHC data analysis and interpretation. DBA conceived and designed the experiments. CC conceived and designed the experiments. SS conceived and designed 16S rRNA sequencing data analysis. XC conceived and designed the experiments, analyzed the data, and wrote the article.

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Correspondence to Xiaoli Chen.

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Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity

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Qiu, X., Macchietto, M.G., Liu, X. et al. Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity. Int J Obes 45, 143–154 (2021). https://doi.org/10.1038/s41366-020-00712-2

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