Open AccessWWP1 knockout in mice exacerbates obesity‐related phenotypes in white adipose tissue but improves whole‐body glucose metabolism
Author(s) -
Hoshino Shunsuke,
Kobayashi Masaki,
Tagawa Ryoma,
Konno Ryutaro,
Abe Takuro,
Furuya Kazuhiro,
Miura Kumi,
Wakasawa Hiroki,
Okita Naoyuki,
Sudo Yuka,
Mizunoe Yuhei,
Nakagawa Yoshimi,
Nakamura Takeshi,
Kawabe Hiroshi,
Higami Yoshikazu
Publication year - 2020
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12795
Subject(s) - medicine , endocrinology , white adipose tissue , ubiquitin ligase , diet induced obese , oxidative stress , adipose tissue , insulin resistance , biology , knockout mouse , carbohydrate metabolism , chemistry , insulin , ubiquitin , biochemistry , receptor , gene
White adipose tissue (WAT) is important for maintenance of homeostasis, because it stores energy and secretes adipokines. The WAT of obese people demonstrates mitochondrial dysfunction, accompanied by oxidative stress, which leads to insulin resistance. WW domain‐containing E3 ubiquitin protein ligase 1 (WWP1) is a member of the HECT‐type E3 family of ubiquitin ligases and is associated with several diseases. Recently, we demonstrated that WWP1 is induced specifically in the WAT of obese mice, where it protects against oxidative stress. Here, we investigated the function of WWP1 in WAT of obese mice by analyzing the phenotype of Wwp1 knockout (KO) mice fed a high‐fat diet. The levels of oxidative stress markers were higher in obese WAT from Wwp1 KO mice. Moreover, Wwp1 KO mice had lower activity of citrate synthase, a mitochondrial enzyme. We also measured AKT phosphorylation in obese WAT and found lower levels in Wwp1 KO mice. However, plasma insulin level was low and glucose level was unchanged in obese Wwp1 KO mice. Moreover, both glucose tolerance test and insulin tolerance test were improved in obese Wwp1 KO mice. These findings indicate that WWP1 participates in the antioxidative response and mitochondrial function in WAT, but knockdown of WWP1 improves whole‐body glucose metabolism.