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.
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