Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1
作者机构:Department of EndocrinologyThe Third Xiangya Hospital of Central South UniversityChangsha410013China Department of Cellular BiologySchool of Life SciencesKey Laboratory of Pediatric Rare DiseasesMinistry of EducationCentral South UniversityChangsha410013China
出 版 物:《Frontiers of Medicine》 (医学前沿(英文版))
年 卷 期:2024年第18卷第1期
页 面:180-191页
核心收录:
学科分类:1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金:supported by the National Natural Science Foundation of China(Nos.82170598,82000427,and 81970403) the Key Research and Development Program of Hunan Province(No.2022sk2034) the Natural Science Foundation of Hunan Province(Nos.2022JJ30058 and 2023JJ20078)
主 题:Lipin3 Lipin1 hypertriglyceridemia obesity mitochondrial dysfunction
摘 要:Lipin proteins including Lipin 1–3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes,which play crucial roles in lipid ***,little is known about the function of Lipin3 in triglyceride(TG)***,we identified a novel mutation(NM_001301860:p.1835AT/p.D612V)of Lipin3 in a large family with hypertriglyceridemia(HTG)and obesity through whole-exome sequencing and Sanger *** studies revealed that the novel variant altered the half-life and stability of the Lipin3 ***,we generated Lipin3 heterozygous knockout(Lipin3-heKO)mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG *** found that Lipin3-heKO mice exhibited obvious obesity,HTG,and non-alcoholic fatty liver *** study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and *** increased expression of Lipin1 in cytosol may contribute to TG anabolism,and the decreased Lipin1 in nucleoplasm can reduce PGC1α,further leading to mitochondrial dysfunction and reduced TG *** study suggested that Lipin3 was a novel disease-causing gene inducing obesity and *** also established a relationship between Lipin3 and mitochondrial dysfunction.