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.
Highlights
Gut microbiota deficient mice demonstrate accelerated glucose clearance
We find that microbiota depletion boosts glucose uptake in brown adipose tissue (BAT) and cecum, but neither white adipose tissue (WAT) nor liver, and this response is dissociated from adaptive thermogenesis
Compared to the specific-pathogen-free mice fed with low fat diet (LFD) and housed under conventional conditions (Control), ABX-treated mice exhibited an improvement in glucose clearance in an intraperitoneal glucose tolerance test at room temperature (22 °C) and cold exposure at 4 °C for 48 h (Fig. 1a)
Summary
Gut microbiota deficient mice demonstrate accelerated glucose clearance. 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. Studies have suggested that browning of white adipose tissue (WAT)[22], hepatic gluconeogenesis[23] or altered cecum enterocyte metabolism[20] may contribute to blood glucose regulation when the gut microbiota is absent. These previous studies reported both antibiotic-treated and germ-free mice have a browning phenotype in their WAT at both room temperature (22 °C) and thermoneutrality (30 °C), and they concluded that the promotion of browning WAT leads to improved glucose tolerance in the microbiota-depleted mice[22]. Further investigation is needed to establish whether the improved glucose metabolism in microbiotadeficient mice is real, and if so, if it stems from browning of WAT, hepatic gluconeogenesis or the activation of other tissues such as BAT
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