Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice

Vishal Singh, Sarah Galla, Rachel M. Golonka, Andrew D. Patterson, Benoit Chassaing, Bina Joe, Matam Vijay-Kumar

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice. Physiol Genomics 52: 314–321, 2020. First published July 6, 2020; doi:10.1152/physi-olgenomics.00118.2019.—Lipocalin 2 (Lcn2) is a multifunctional innate immune protein that limits microbial overgrowth. Our previous study demonstrated that the gut microbiota directly induces intestinal Lcn2 production, and Lcn2-deficient (Lcn2-/-) mice exhibit gut dysbiosis. Coincidentally, gut dysbiosis is associated with metabolic syndrome pathogenesis, and elevated Lcn2 levels has been considered a potential clinical biomarker of metabolic syndrome. Yet whether Lcn2 mitigates or exacerbates metabolic syndrome remains inconclu-sive. Our objective was to determine whether Lcn2 deficiency-in-duced compositional changes in gut microbiota contribute to gain in adiposity in aged mice. Utilizing Lcn2-/- mice and their wild-type (WT) littermates, we measured metabolic markers, including fasting blood glucose, serum lipids, fat pad weight, and insulin resistance at ages 3, 6, and 9 mo old. Relative to WT mice, aged Lcn2-/- mice exhibited a gain in adiposity associated with numerous features of metabolic syndrome, including insulin resistance and dyslipidemia. Surprisingly, supplementation with a high-fat diet did not further aggravate metabolic syndrome that spontaneously occurs in Lcn2-/- mice by 6 mo of age. Interestingly, chow-fed Lcn2-/- mice displayed marked differences in the bacterial abundance and metabolomic profile of the gut microbiota compared with WT mice. Overall, our results demonstrate that Lcn2 is essential to maintain metabolic and gut microbiotal homeostasis, where deficiency induces spontaneous delayed onset of metabolic syndrome.

Original languageEnglish (US)
Pages (from-to)314-321
Number of pages8
JournalPhysiological genomics
Volume52
Issue number8
DOIs
StatePublished - Aug 2020

All Science Journal Classification (ASJC) codes

  • Physiology
  • Genetics

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