Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Physiol Behav. 2013 Jun 13;118:144-51. doi: 10.1016/j.physbeh.2013.05.015. Epub 2013 May 14.
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.
GPRC6A 是一种在大脑和骨骼肌中高度表达的氨基酸感应受体。尽管最近的证据表明，经过基因工程改造的 GPRC6A 受体敲除（KO）小鼠易发生轻微的内分泌和代谢紊乱，但能量代谢的潜在紊乱在很大程度上仍未得到探索。基于 GPRC6A 的表达模式和配体偏好，我们假设该受体可能通过调节身体活动水平来影响能量代谢。因此，在本研究中，我们使 GPRC6A 受体 KO 小鼠及其野生型（WT）同窝仔鼠暴露于自愿轮式跑步和强制跑步机运动中。此外，我们评估了基础状态下的能量消耗，并评估了轮式跑步对食物摄入、身体成分以及一系列运动诱导的中枢和外周生物标志物的影响。我们发现，对自愿轮式跑步的适应受到 GPRC6A 的影响，因为该受体的缺失会显著增强 KO 相对于 WT 小鼠的轮式跑步。两种基因型都通过增加食物摄入和改善身体成分来对自愿运动做出类似的反应。总之，这些数据表明，GPRC6A 受体参与调节运动行为。未来的研究非常有必要阐明其潜在的分子细节，并评估这些发现是否具有任何转化价值。
