FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1

Area of Science:

• Metabolic research
• Endocrinology
• Thermogenesis

Background:

• Fibroblast growth factor 21 (FGF21) is linked to weight loss and improved glucose metabolism.
• Increased uncoupling protein 1 (UCP1) in adipose tissue suggests UCP1-dependent thermogenesis drives FGF21 action.
• Previous studies indicated FGF21 improves glucose homeostasis independently of UCP1.

Purpose of the Study:

• To investigate the role of uncoupling protein 1 (UCP1) in mediating the effects of Fibroblast growth factor 21 (FGF21) on glucose metabolism and thermogenesis.
• To determine if FGF21-mediated weight loss and glucose improvements are dependent on UCP1.
• To examine the impact of FGF21 on brown adipose tissue (BAT) temperature during glucose challenges in the presence and absence of UCP1.

Main Methods:

• Comparison of FGF21 effects on wild-type and Ucp1 knockout mice.
• Assessment of body weight and glucose homeostasis.
• Measurement of brown adipose tissue (BAT) temperature during glucose excursions.

Main Results:

• FGF21 reduced body weight in both wild-type and Ucp1 knockout mice.
• Rapid glucose clearance by FGF21 was impaired in Ucp1 knockout mice.
• FGF21 prevented the fall in BAT temperature during glucose challenges in wild-type mice, an effect lost in Ucp1 knockout mice.

Conclusions:

• FGF21-mediated improvements in clearing a glucose challenge require UCP1.
• FGF21 utilizes UCP1-dependent thermogenesis to enhance glucose disposal.
• UCP1 is essential for FGF21's beneficial effects on glucose metabolism, likely through thermogenesis.