Dissociation of Adaptive Thermogenesis from Glucose Homeostasis in Microbiome-Deficient Mice

Publication Type Academic Article
Authors Krisko TI, Nicholls HT, Bare CJ, Holman CD, Putzel GG, Jansen RS, Sun N, Rhee KY, Banks AS, Cohen DE
Journal Cell Metab
Volume 31
Issue 3
Pagination 592-604.e9
Date Published 03/03/2020

Recent studies suggest that a key mechanism whereby the gut microbiome influences energy balance and glucose homeostasis is through the recruitment of brown and beige adipocytes, primary mediators of the adaptive thermogenic response. To test this, we assessed energy expenditure and glucose metabolism in two complementary mouse models of gut microbial deficiency, which were exposed to a broad range of thermal and dietary stresses. Neither ablation of the gut microbiome, nor the substantial microbial perturbations induced by cold ambient temperatures, influenced energy expenditure during cold exposure or high-fat feeding. Nevertheless, we demonstrated a critical role for gut microbial metabolism in maintaining euglycemia through the production of amino acid metabolites that optimized hepatic TCA (tricarboxylic acid) cycle fluxes in support of gluconeogenesis. These results distinguish the dispensability of the gut microbiome for the regulation of energy expenditure from its critical contribution to the maintenance of glucose homeostasis.

DOI 10.1016/j.cmet.2020.01.012
PubMed ID 32084379
PubMed Central ID PMC7888548