骨钙素是骨细胞外基质的重要组分，研究发现其与能量及糖脂代谢关系密切。但骨钙素调控肝脏脂质代谢的机制仍知之甚少。我们预实验结果提示外源性骨钙素干预可改善高脂饮食喂养小鼠肝脏糖脂代谢及脂质沉积；骨钙素特异性受体—G蛋白偶联受体C家族6组成员A（GPRC6A）在小鼠肝细胞表达。为此，我们提出假说：骨钙素可能通过与肝细胞GPRC6A结合后，减轻氧化应激、凋亡及自噬，从而改善肝脏脂质代谢并减轻肝脏脂质沉积。为验证这一假说，我们将通过骨钙素基因敲除小鼠、GPRC6A基因肝脏条件性敲除小鼠、高脂饮食诱导的肝脏脂质沉积小鼠模型，小鼠原代肝细胞、人体肝脏组织，采用real-time PCR、Western blot、RNA干扰、免疫组化等方法，从整体、组织、细胞及分子等层面明确骨钙素及GPRC6A在维持肝脏脂质代谢稳态及改善肝脏脂质沉积中的作用及其调控机制，为寻找骨钙素在维持脂代谢稳态中的作用提供新的思路。

As an important component of bone extracellular matrix, osteocalcin has been found closely associated with energy, glucose, and lipid metabolism. However, little has been known about the relationship between osteocalcin and liver lipid metabolism. Our pilot experiments suggested that treatment with exogenous osteocalcin could improve liver glucose and lipid metabolism, alleviate liver fat deposition in mouse on high-fat diets; G protein coupled receptor, family C group 6 subtype A (GPRC6A), an osteocalcin-specific receptor, was expressed in mouse liver cells. Thus, it is warrant to hypothesize that osteocalcin may affect the oxidative stress, apoptosis and autophagy by binding with GPRC6A, leading to an improved liver lipid metabolism and reduced liver fat deposition. To verify this hypothesis, we aim to investigate the regulatory mechanism of osteocalcin and its receptor GPRC6A on liver lipid metabolic homeostasis by means of real-time PCR, Western blot, RNA interference, and immunohistochemistry from different aspects of animals, tissues, cells, and molecules. Osteocalcin gene knockout mice, GPRC6A gene liver conditional knockout mice, high fat diet induced mouse model of liver lipidosis, mice primary hepatocytes and human liver tissue will be involved. This study may provide new insights into the influence of osteocalcin on liver lipid metabolic homeostasis from a new perspective of osteocalcin and its receptor-GPRC6A.