Exercise enhancement by RGS14 disruption is mediated by brown adipose tissue

Area of Science:

• Physiology
• Metabolism
• Aging Research

Background:

• Enhanced exercise capacity is crucial for healthy aging and cardiovascular disease therapy.
• Disruption of Regulator of G Protein Signaling 14 (RGS14) in mice extends lifespan, mediated by brown adipose tissue (BAT).

Purpose of the Study:

• To investigate if RGS14 knockout (KO) mice exhibit enhanced exercise capacity.
• To determine the role of BAT in mediating exercise capacity in RGS14 KO mice.

Main Methods:

• Exercise capacity was assessed in RGS14 KO and wild-type (WT) mice using treadmill tests (maximal running distance, work to exhaustion).
• BAT transplantation experiments were conducted using RGS14 KO and WT mice to evaluate BAT's role.
• Mechanisms including mitochondrial biogenesis, antioxidant defense, and hindlimb perfusion were examined.

Main Results:

• RGS14 KO mice displayed a 160% increase in maximal running distance and 154% increase in work to exhaustion compared to WT mice.
• BAT transplantation from RGS14 KO mice to WT mice reversed the phenotype, significantly increasing exercise performance.
• Enhanced exercise capacity was mediated by mitochondrial biogenesis, SIRT3, antioxidant defense, the MEK/ERK pathway, and increased hindlimb perfusion.

Conclusions:

• Brown adipose tissue (BAT) mediates enhanced exercise capacity.
• RGS14 disruption potentiates the effects of BAT on exercise performance.
• These findings highlight BAT as a therapeutic target for improving exercise capacity in aging and cardiovascular disease.