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 between 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 metabolism occurs earlier than other pathophysiological abnormalities during fructose overconsumption in humans. This is a potential confounding factor for studies relying on 18 F-FDG to assess BAT thermogenesis. • Fructose overfeeding decreases brown adipose tissue glucose metabolism • These changes occur independently of oxidative metabolism • No change is observed with glucose overfeeding • The gut microbiome is not affected by fructose/glucose overfeeding Richard et al. show that after 2 weeks of fructose overfeeding, brown adipose tissue (BAT) glucose consumption decreases independently of changes in thermogenesis and gut microbiome. This impairment of BAT function does not occur with glucose overfeeding and is a very early sign of fructose-induced dysmetabolism.