Serum FGF21 levels are associated with brown adipose tissue activity in humans
Mark J W Hanssen1, Evie Broeders2, Ricardo J Samms3
1Department of Human Biology, NUTRIM School for Nutrition and Translational Research in Metabolism,Maastricht University Medical Centre+(MUMC+), Maastricht, the Netherlands.
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 [(18)F]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.
Insights
Fibroblast growth factor 21 (FGF21) levels correlate with brown adipose tissue (BAT) activity in humans. This suggests FGF21 may enhance BAT function, offering a potential therapeutic target for obesity and metabolic disorders.
Area of Science:
- Metabolic research
- Obesity research
- Endocrinology
Background:
- The global obesity pandemic necessitates new therapeutic strategies for metabolic complications.
- Brown adipose tissue (BAT) reactivation in humans presents a promising target for energy homeostasis.
- Fibroblast growth factor 21 (FGF21) shows potential in preclinical models for treating obesity-related metabolic issues.
Purpose of the Study:
- To investigate the relationship between plasma FGF21 levels and BAT activity in human subjects.
- To explore FGF21's role in thermogenesis and normothermia regulation during cold exposure.
- To assess the impact of cold acclimation on BAT activity and FGF21 levels.
Main Methods:
- Measured plasma FGF21 levels in two human cohorts.
- Assessed BAT activity using [(18)F]FDG-PET/CT scans under a personalized cooling protocol.
- Monitored core body temperature changes during acute cold exposure.
Main Results:
- Circulating FGF21 levels positively correlated with BAT activity in males during acute cold exposure.
- FGF21 levels were associated with changes in core body temperature, suggesting a role in normothermia maintenance.
- Cold acclimation led to increased BAT activity and concurrently elevated FGF21 levels.
Conclusions:
- Human plasma FGF21 levels are linked to BAT activity.
- FGF21 may be a key mediator in enhancing human BAT function.
- These findings suggest FGF21 as a potential therapeutic target for metabolic diseases by modulating BAT activity.
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