人脂素基因LIPIN1在酵母中的异源表达及细胞功能分析

Expression of Human LIPIN1 Gene and Its Functional Analysis in Yeast

脂类代谢调控是维持生物体能量平衡的重要环节,脂类代谢调控的紊乱与肥胖症、糖尿病和高血压等疾病密切相关。脂素基因LIPIN1是诱导脂肪细胞分化、调控脂类合成的关键基因,其编码的磷脂磷酸酶(phosphatidate phosphatase,PAP)在人体三酰甘油合成中起关键作用,是维持人体脂类平衡的重要保障。此外,该基因还作为重要的转录辅激活因子参与多种生长及营养代谢调控。多种生物中均有类似功能的基因被发现,暗示了其功能的多样性及物种间的保守性。该文利用酿酒酵母在脂类代谢研究中性状易于表征、同源基因PAH1功能明确的优势,通过同源重组技术构建脂素缺陷型酵母,探索脂素基因在维持酵母正常生长及脂类合成中的重要作用,并通过功能互补及生物信息学技术对比分析了人源LIPIN1基因与酵母PAH1基因编码蛋白在结构和功能上的保守性,为脂素基因LIPIN1的细胞功能研究提供基础数据。

The regulation of lipid metabolism is important in maintaining the energy balance. Its disorder induces many diseases, such as obesity, diabetes, high blood pressure and so on. LIPIN1, a key gene for adipocyte differentiation induction and lipids synthesis regulation, encodes phospholipids phosphatase （PAP） and plays an important role in triglyceride synthesis and lipids homeostasis in human. In addition, LIPIN1 acts as a transcriptional coactivator in various regulations of nutrition and growth metabolism, and many similar genes have been found in other species, indicating its various functions and species conservation. In this paper, we constructed PAH1 mutant yeast and transformed it with human LIPIN1 to study effects of LIPIN1 on yeast growth and lipid synthesis based on the convenience of Saccharomyces cerevisiae in lipid metabolism study and phenotypic observation, and the clearity of cellular function of PAH1. Thereafter, we compared LIPINlp with PAHlp in structure and function via functional complementation analysis and bioinformatics, and confirmed the functional conservation of PAP in human and yeast. This work will provide evidence for the cellular function study of LIPIN1.