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Impaired Peroxisomal Fitness in Obese Mice, a Vicious Cycle Exacerbating Adipocyte Dysfunction via Oxidative Stress

Title
Impaired Peroxisomal Fitness in Obese Mice, a Vicious Cycle Exacerbating Adipocyte Dysfunction via Oxidative Stress
Authors
Piao, LingjuanDorotea, DebraJiang, SonglingKoh, Eun HeeOh, Goo TaegHa, Hunjoo
Ewha Authors
하헌주오구택
SCOPUS Author ID
하헌주scopus; 오구택scopus
Issue Date
2019
Journal Title
ANTIOXIDANTS & REDOX SIGNALING
ISSN
1523-0864JCR Link

1557-7716JCR Link
Citation
ANTIOXIDANTS & REDOX SIGNALING vol. 31, no. 18, pp. 1339 - 1351
Keywords
obesityperoxisomewhite adipose tissuecatalasePPAR alphafenofibrate
Publisher
MARY ANN LIEBERT, INC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Aims: Peroxisome is a critical organelle for fatty acid oxidation (FAO) and metabolism of reactive oxygen species (ROS). Increased oxidative stress in adipose tissue contributes to the development of insulin resistance and metabolic syndrome in obesity. This study aimed to investigate the role of peroxisomal fitness in maintaining adipocyte function, which has been under-rated in the obesity research area. Results: Reduced peroxisomal gene expressions in white adipose tissue (WAT) of obese mice suggested a close correlation between peroxisomes and obesity. Peroxisomal biogenesis factor 5 siRNA increased cellular ROS and inflammatory mediators in 3T3-L1 adipocytes. On the contrary, hydrogen peroxide or tumor necrosis factor-alpha treatment significantly decreased biogenesis- and function-related peroxisomal proteins, suggesting a positive feedback loop of ROS/inflammation and peroxisomal dysfunction. Correspondingly, catalase (a major peroxisomal antioxidant)-knockout mice fed with high-fat diet (HFD) exhibited suppressed peroxisomal proteins along with increased oxidative stress and accelerated obesity. In response to fenofibrate (a peroxisomal proliferator) treatment, WAT of HFD-fed wild-type mice showed not only increases in peroxisomal biogenesis and FAO but also attenuated features of adipocyte dysfunction and obesity. However, these results were not observed in peroxisome proliferator-activated receptor-alpha null obese mice. Innovation: Impaired peroxisomal fitness enhanced oxidative stress and inflammation in adipocytes, which exacerbates obesity. Conclusion: Adipose tissue peroxisomal homeostasis plays an important role in attenuating the features of obesity, and it can be a potential therapeutic target of obesity.
DOI
10.1089/ars.2018.7614
Appears in Collections:
약학대학 > 약학과 > Journal papers
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