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The Vitamin K Epoxide Reductase Vkorc1l1 Promotes Preadipocyte Differentiation in Mice
Author(s) -
Ding Yi,
Cui Jing,
Wang Qi,
Shen Suqin,
Xu Tian,
Tang Huiru,
Han Min,
Wu Xiaohui
Publication year - 2018
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.22206
Subject(s) - adipogenesis , adipose tissue , endocrinology , medicine , stromal vascular fraction , gene knockdown , intracellular , white adipose tissue , vitamin , chemistry , biology , microbiology and biotechnology , biochemistry , gene
Objective Identification of novel regulators involved in adipose development is important to understand the molecular mechanism underlying obesity and associated metabolic disorders. Through isolation and analysis of a vitamin K epoxide reductase Vkorc1l1 mutant, this study aimed to disclose its function and underlying mechanism in adipose development and to obtain valuable insights regarding the mechanism of obesity. Methods A Vkorc1l1 mutation recovered from a forward genetic screen for obesity‐related loci in mice was characterized to explore its effects in gene expression, animal metabolism, and adipose development. Adipogenesis was evaluated in both Vkorc1l1 mutant stromal vascular fraction and Vkorc1l1 knockdown preadipocytes. Intracellular vitamin K 2 level and the effect of vitamin K 2 on adipogenesis were tested in primary preadipocytes. Results Vkorc1l1 mutants displayed a considerably lower fat to body weight ratio, substantially decreased plasma leptin, and significantly underdeveloped white adipose tissue. Adipogenic defects related with Vkorc1l1 deficiency were observed both in vivo and in vitro . Vitamin K 2 could inhibit adipogenesis in stromal vascular fraction. Increased intracellular vitamin K 2 level was detected in Vkorc1l1 mutant preadipocytes. Conclusions Vkorc1l1 promotes adipogenesis and possibly obesity. Downregulation of Vkorc1l1 increases intracellular vitamin K 2 level and impedes preadipocyte differentiation.