GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance
JooYeon Jhun,
Jin Seok Woo,
Seung Hoon Lee,
Jeong-Hee Jeong,
KyungAh Jung,
Wonhee Hur,
Seon-Yeong Lee,
Jae Yoon Ryu,
Young-Mee Moon,
Yoon Ju Jung,
Kyo Young Song,
Kiyuk Chang,
Seung Kew Yoon,
Sung-Hwan Park,
Mi-La Cho
Affiliations
JooYeon Jhun
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea
Jin Seok Woo
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea
Seung Hoon Lee
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
Jeong-Hee Jeong
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea
KyungAh Jung
Research Center, Impact Biotech, Seoul 137-040, Korea
Wonhee Hur
The Catholic University Liver Research Center & WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea
Seon-Yeong Lee
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea
Jae Yoon Ryu
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea
Young-Mee Moon
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea
Yoon Ju Jung
Division of Gastrointestinal Surgery, Department of General Surgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 137-040, Korea
Kyo Young Song
Division of Gastrointestinal Surgery, Department of General Surgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 137-040, Korea
Kiyuk Chang
Cardiovascular Center and Cardiology Division, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea
Seung Kew Yoon
The Catholic University Liver Research Center & WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea
Sung-Hwan Park
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea
Mi-La Cho
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea
Obesity, a condition characterized by excessive accumulation of body fat, is a metabolic disorder related to an increased risk of chronic inflammation. Obesity is mediated by signal transducer and activator of transcription (STAT) 3, which is regulated by genes associated with retinoid-interferon-induced mortality (GRIM) 19, a protein ubiquitously expressed in various human tissues. In this study, we investigated the role of GRIM19 in diet-induced obese C57BL/6 mice via intravenous or intramuscular administration of a plasmid encoding GRIM19. Splenocytes from wild-type and GRIM19-overexpressing mice were compared using enzyme-linked immunoassay, real-time polymerase chain reaction, Western blotting, flow cytometry, and histological analyses. GRIM19 attenuated the progression of obesity by regulating STAT3 activity and enhancing brown adipose tissue (BAT) differentiation. GRIM19 regulated the differentiation of mouse-derived 3T3-L1 preadipocytes into adipocytes, while modulating gene expression in white adipose tissue (WAT) and BAT. GRIM19 overexpression reduced diet-induced obesity and enhanced glucose and lipid metabolism in the liver. Moreover, GRIM19 overexpression reduced WAT differentiation and induced BAT differentiation in obese mice. GRIM19-transgenic mice exhibited reduced mitochondrial superoxide levels and a reciprocal balance between Th17 and Treg cells. These results suggest that GRIM19 attenuates the progression of obesity by controlling adipocyte differentiation.
