钙离子信号对肠道脂类吸收代谢的调控

脂代谢的失调与代谢紊乱性疾病如肥胖和糖尿病的发生密切相关。中性脂肪在肠道内的吸收和转运是脂代谢的关键一环，但其分子机制亟待进一步阐明。果蝇和哺乳动物的肠道在解剖结构和功能上具有高度相似性。我们拟以果蝇为模型研究肠道脂吸收及代谢机制。本课题组已发表成果显示胞浆钙离子信号（cytoCa2+）整合上游信号调控果蝇肠道干细胞增殖。初步结果表明中性脂肪在成虫肠道内呈区域性分布，且与胞浆Ca2+浓度密切相关。进一步发现，转录激活子CRTC受Ca2+调节通过下调脂肪酶Magro转录, 进而抑制脂肪降解和吸收。这些结果表明Ca2+/CRTC/Magro 通路调节脂类在肠细胞中的吸收。本课题拟进一步解析果蝇肠细胞cytoCa2+和脂类分布的时空动态模式，阐明Ca2+调控脂类吸收代谢的信号通路，并揭示Ca2+信号通路在高脂、高糖等果蝇模型中的作用，为代谢紊乱疾病的治疗提供新的潜在靶点。

Dysregulation of lipid metabolism is closely related to the occurrence of metabolic disorders such as obesity and diabetes. The absorption and transport of neutral fat in the intestine is essential for lipid metabolism, while its molecular mechanism needs to be further clarified. The intestines of Drosophila and mammals are highly similar in anatomical structure and function. We sought to study the mechanism of intestinal lipid uptake and metabolism using Drosophila as a model. We previously have shown that cytosolic Calcium (cytoCa2+) integrates upstream signals to regulate intestinal stem cell proliferation in Drosophila. Our preliminary results here showed that the neutral fat was regional distributed along the gut, and was closely related to the cytosolic Ca2+ level. We further found that the transcriptional activator CRTC functions downstream of cytoCa2+ to suppress transcription of the lipase Magro, thereby inhibiting dietary fat degradation and absorption. These results indicate that the Ca2+/ CRTC/Magro pathway inhibits lipid uptake in intestinal cells. Our ongoing research intends to further analyze the dynamic pattern of cytoCa2+ and lipid distribution in the gut, decode the components of cytoCa2+ signaling pathway regulating lipid absorption and metabolism, and reveal the role of Ca2+ signaling pathways in Drosophila high-fat or high sugar models. Our research will provide novel therapeutic targets for treatment of metabolic syndromes, such as obesity and diabetes.