TY - JOUR

T1 - Enhanced voluntary wheel running in GPRC6A receptor knockout mice

AU - Clemmensen, Christoffer

AU - Pehmøller, Christian

AU - Klein, Anders B

AU - Ratner, Cecilia

AU - Wojtaszewski, Jørgen

AU - Bräuner-Osborne, Hans

N1 - CURIS 2013 NEXS 105

PY - 2013

Y1 - 2013

N2 - GPRC6A is an amino acid-sensing receptor highly expressed in the brain and in skeletal muscle. Although recent evidence suggests that genetically engineered GPRC6A receptor knockout (KO) mice are susceptible to develop subtle endocrine and metabolic disturbances, the underlying disruptions in energy metabolism are largely unexplored. Based on GPRC6A's expression pattern and ligand preferences, we hypothesize that the receptor may impact energy metabolism via regulating physical activity levels. Thus, in the present study, we exposed GPRC6A receptor KO mice and their wild-type (WT) littermates to voluntary wheel running and forced treadmill exercise. Moreover, we assessed energy expenditure in the basal state, and evaluated the effects of wheel running on food intake, body composition, and a range of exercise-induced central and peripheral biomarkers. We found that adaptation to voluntary wheel running is affected by GPRC6A, as ablation of the receptor significantly enhances wheel running in KO relative to WT mice. Both genotypes responded to voluntary exercise by increasing food intake and improving body composition to a similar degree. In conclusion, these data demonstrate that the GPRC6A receptor is involved in regulating exercise behaviour. Future studies are highly warranted to delineate the underlying molecular details and to assess if these findings hold any translational value.

AB - GPRC6A is an amino acid-sensing receptor highly expressed in the brain and in skeletal muscle. Although recent evidence suggests that genetically engineered GPRC6A receptor knockout (KO) mice are susceptible to develop subtle endocrine and metabolic disturbances, the underlying disruptions in energy metabolism are largely unexplored. Based on GPRC6A's expression pattern and ligand preferences, we hypothesize that the receptor may impact energy metabolism via regulating physical activity levels. Thus, in the present study, we exposed GPRC6A receptor KO mice and their wild-type (WT) littermates to voluntary wheel running and forced treadmill exercise. Moreover, we assessed energy expenditure in the basal state, and evaluated the effects of wheel running on food intake, body composition, and a range of exercise-induced central and peripheral biomarkers. We found that adaptation to voluntary wheel running is affected by GPRC6A, as ablation of the receptor significantly enhances wheel running in KO relative to WT mice. Both genotypes responded to voluntary exercise by increasing food intake and improving body composition to a similar degree. In conclusion, these data demonstrate that the GPRC6A receptor is involved in regulating exercise behaviour. Future studies are highly warranted to delineate the underlying molecular details and to assess if these findings hold any translational value.

U2 - 10.1016/j.physbeh.2013.05.015

DO - 10.1016/j.physbeh.2013.05.015

M3 - Journal article

C2 - 23680430

VL - 118

SP - 144

EP - 151

JO - Physiology & Behavior

JF - Physiology & Behavior

SN - 0031-9384

ER -