Abstract
The obesity pandemic has spurred a need for novel therapies to prevent and treat metabolic complications. The recent rediscovery of brown adipose tissue (BAT) in humans made this tissue a possible therapeutic target, due to its potentially substantial contributions to energy homeostasis. Fibroblast growth factor 21 (FGF21) has been identified as a facilitator of cold-induced thermogenesis in humans. Furthermore, pre-clinical studies revealed that FGF21 administration leads to improvement in the metabolic consequences of obesity, such as dyslipidemia and type 2 diabetes. Here we studied plasma FGF21 levels in two cohorts of human subjects, in whom BAT activity was determined using an individualized cooling protocol by [18F]FDG-PET/CT scan. Importantly, we found that circulating FGF21 levels correlated with BAT activity during acute cold exposure in male subjects. In addition, FGF21 levels were related to the change in core temperature upon acute cold exposure, indicating a role for FGF21 in maintaining normothermia, possibly via activation of BAT. Furthermore, cold acclimation increased BAT activity in parallel with increased FGF21 levels. In conclusion, our results demonstrate that FGF21 levels in humans are related to BAT activity, suggesting that FGF21 may represent a novel mechanism via which BAT activity in humans may be enhanced.
Highlights
Effects are translatable to humans[10]
Our data show that serum Fibroblast growth factor-21 (FGF21) levels correlate positively with cold-induced brown adipose tissue activity in humans
We show that FGF21 levels are increased upon a 10-day cold acclimation period, in parallel with increased brown adipose tissue (BAT) activity
Summary
Effects are translatable to humans[10]. chronic treatment with varying doses of LY2405319 resulted in improvements in plasma lipid profiles, and decreases in fasting insulin levels and body weight. Cold exposure has been reported to increase circulating levels of FGF21 besides enhanced FGF21 expression in BAT, leading to uncoupling protein-1 (UCP-1) transcription[8,19,20]. We studied the relationship between circulating FGF21 levels and BAT activity and the effect of acute and prolonged cold exposure (cold acclimation) on these parameters. To this end, we measured plasma FGF21 levels in a large number of subjects from previous studies[13,24,25,26], who were exposed to an individualized cooling protocol[27] for evaluation of BAT activity using an [18F]FDG-PET/CT scan. Chronic cold acclimation increases BAT activity in parallel with an increase in FGF21 levels
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