Abstract

Gut microbiota deficient mice demonstrate accelerated glucose clearance. However, which tissues are responsible for the upregulated glucose uptake remains unresolved, with different studies suggesting that browning of white adipose tissue, or modulated hepatic gluconeogenesis, may be related to enhanced glucose clearance when the gut microbiota is absent. Here, we investigate glucose uptake in 22 different tissues in 3 different mouse models. We find that gut microbiota depletion via treatment with antibiotic cocktails (ABX) promotes glucose uptake in brown adipose tissue (BAT) and cecum. Nevertheless, the adaptive thermogenesis and the expression of uncoupling protein 1 (UCP1) are dispensable for the increased glucose uptake and clearance. Deletion of Ucp1 expressing cells blunts the improvement of glucose clearance in ABX-treated mice. Our results indicate that BAT and cecum, but not white adipose tissue (WAT) or liver, contribute to the glucose uptake in the gut microbiota depleted mouse model and this response is dissociated from adaptive thermogenesis. Gut microbiota deficient mice demonstrate enhanced glucose clearance, but which tissues are responsible for this improvement are still unclear. Here the authors report that brown adipose tissue contributes to the enhanced glucose clearance in gut microbiota depleted mice and that this response is dissociated from adaptive thermogenesis.

Original languageEnglish
Article number4725
Number of pages13
JournalNature Communications
Volume12
Issue number1
Early online date5 Aug 2021
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Acknowledgements
This work was supported by the National Natural Science Foundation of China (92057206), the KC Wong Education Foundation, as well as grants from the ‘1000 talents’ recruitment program, a PIFI professorial fellowship from CAS and a Wolfson merit professorship from the UK Royal Society, all to J.R.S. We are grateful to all the members of the Molecular Energetics Group for their support and discussion of the results. We would like to thank Peter Thomson and Marina Stamatiou for technical assistance with the DLW measurements.

Data Availability Statement

All raw data generated or analyzed during this study are in this published articles and its supplementary information files. Source data are provided with this paper.

Keywords

  • MITOCHONDRIAL UNCOUPLING PROTEIN
  • DIET-INDUCED THERMOGENESIS
  • GUT MICROBIOTA
  • NONSHIVERING THERMOGENESIS
  • ENERGY-EXPENDITURE
  • INDUCED OBESITY
  • METABOLISM
  • UCP1
  • HOMEOSTASIS
  • ADIPOCYTES

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