Abstract
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.
Highlights
White adipose tissue (WAT) is important for maintenance of homeostasis, because it stores energy in the form of triglyceride and secretes adipokines that affect energy metabolism by modulating the activities of adiponectin, leptin, and proinflammatory cytokines
We showed that WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) deficiency reduced the GSH/GSSG ratio because of increased concentration of GSSG in obese WAT
We found that 4-HNE concentrations were similar in WT and KO mice and in the normal diet (ND)- and high-fat diet (HFD)-fed groups
Summary
White adipose tissue (WAT) is important for maintenance of homeostasis, because it stores energy in the form of triglyceride and secretes adipokines that affect energy metabolism by modulating the activities of adiponectin, leptin, and proinflammatory cytokines. Hypertrophy of mature adipocytes disrupts the balance in adipokine secretion, as it is accompanied by reduction in adiponectin secretion and increased release of proinflammatory cytokines that induce systemic insulin resistance, chronic inflammation, and oxidative stress [1,2]. Mitochondria in WAT of obese people produce more ROS and express increased levels of markers of oxidative damage [10]. These observations indicate that oxidative stress because of increased mitochondrial ROS contributes to obesity-related pathologies. It is likely that WWP1 is involved in determining the phenotype of adipocytes. We found that WWP1 is induced in obese mouse WAT and is protective against oxidative stress in adipocytes [23]. In the present study, we explored the function of WWP1 in obese WAT and whole-body glucose metabolism by analyzing the phenotype of obese Wwp knockout (KO) mice
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