High-fructose Feeding Suppresses Cold-Stimulated Brown Adipose Tissue Glucose Uptake Independently of Changes in Thermogenesis and the Gut Microbiome

Diets rich in added sugars are associated with metabolic diseases, and studies have shown a link between these pathologies and changes in the microbiome. Given the reported associations in animal models be-tween the microbiome and brown adipose tissue (BAT) function, and the alterations in the microbiome induced by high-glucose or high-fructose diets, we investigated the potential causal link between high -glucose or-fructose diets and BAT dysfunction in humans. Primary outcomes are changes in BAT cold -induced thermogenesis and the fecal microbiome (clinicaltrials.gov, NCT03188835). We show that BAT glucose uptake, but not thermogenesis, is impaired by a high-fructose but not high-glucose diet, in the absence of changes in the gastrointestinal microbiome. We conclude that decreased BAT glucose meta-bolism occurs earlier than other pathophysiological abnormalities during fructose overconsumption in hu-mans. This is a potential confounding factor for studies relying on F-18-FDG to assess BAT thermogenesis.