维生素D(VD)缺乏是一个全球性的公共健康问题。肥胖及相关疾病（高脂血症、胰岛素抵抗、2型糖尿病）人群存在VD缺乏，且VD补充效果差，其机制尚不清楚。我们预实验发现高脂饮食诱导的肥胖及糖脂代谢紊乱小鼠血清25(OH)D水平、肝脏25(OH)D合成酶CYP2R1的表达均显著低于对照小鼠；高胆固醇饮食小鼠肝脏CYP2R1表达也显著低于对照小鼠。这些结果提示肥胖及相关疾病可能通过影响肝脏/肾脏VD代谢而导致VD缺乏、降低VD补充效果。本课题拟进一步通过动物、细胞和分子水平的研究，探讨肥胖及相关糖脂代谢紊乱、高胆固醇饮食在VD缺乏中的作用及机制、以及对VD补充效力的影响；探讨通过减肥纠正糖脂代谢紊乱是否通过改善VD代谢而纠正VD缺乏。本研究不仅能揭示肥胖及相关疾病发生VD缺乏的机制，而且能为纠正肥胖及相关疾病VD缺乏、提高VD补充效果提供新对策，具有重要的理论意义和潜在的临床价值。

Vitamin D deficiency is a global health problem. Patients with obesity and related diseases, including hyperlipidemia, insulin resistance and type 2 diabetes, have vitamin D deficiency, and poorly respond to vitamin D supplementation. The underlying mechanisms are unclear. Our preliminary results showed that high fat diet-induced obese mice had lower serum 25(OH)D level and hepatic 25(OH)D synthesize enzyme (CYP2R1) expression than control chow fed mice. Hepatic CYP2R1 expression was also decreased in high cholesterol diet fed mice. These results indicate that vitamin D deficiency in obesity and related diseases may result from impaired vitamin D metabolism in liver and kidney, which reduces 25(OH)D production after vitamin D supplementation. In this project, we will investigate the involvement of glucose and lipid dysmetabolism in vitamin D deficiency, and examine if weight loss could improve vitamin D metabolism and vitamin D deficiency. Our study will not only reveal the mechanisms underlying vitamin D deficiency in obesity and related diseases, but also provide approach to alleviate vitamin D deficiency and improve efficiency for vitamin D supplementation.