WWP1 knockout in mice exacerbates obesity‐related phenotypes in white adipose tissue but improves whole‐body glucose metabolism

Autor: Takeshi Nakamura, Ryutaro Konno, Yuka Sudo, Kazuhiro Furuya, Hiroki Wakasawa, Takuro Abe, Kumi Miura, Masaki Kobayashi, Hiroshi Kawabe, Shunsuke Hoshino, Ryoma Tagawa, Yoshikazu Higami, Naoyuki Okita, Yoshimi Nakagawa, Yuhei Mizunoe
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
obesity
White adipose tissue
medicine.disease_cause
Mice
0302 clinical medicine
Citrate synthase
Homeostasis
Insulin
lcsh:QH301-705.5
Research Articles
Mice
Knockout
Glucose tolerance test
biology
medicine.diagnostic_test
Ubiquitin ligase
Mitochondria
WWP1
Phenotype
030220 oncology & carcinogenesis
Carbohydrate Metabolism
Female
Research Article
medicine.medical_specialty
Adipose Tissue
White
Ubiquitin-Protein Ligases
Carbohydrate metabolism
Diet
High-Fat
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Insulin resistance
white adipose tissue
mitochondrial function
Internal medicine
medicine
Animals
Insulin tolerance test
medicine.disease
Lipid Metabolism
antioxidative capacity
Oxidative Stress
030104 developmental biology
Endocrinology
Glucose
lcsh:Biology (General)
biology.protein
Insulin Resistance
Energy Metabolism
Oxidative stress
Zdroj: FEBS Open Bio, Vol 10, Iss 3, Pp 306-315 (2020)
FEBS Open Bio
ISSN: 2211-5463
Popis: 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.
WWP1 knockout mice fed high‐fat diet have suppressed mitochondrial enzymatic activity and exacerbated oxidative stress in white adipose tissue, but decreased blood insulin levels and enhanced insulin sensitivity, resulting in improved glucose metabolism in whole body.
Databáze: OpenAIRE
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