GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance
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-in...
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2021-01-01
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author | 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 |
author_facet | 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 |
author_sort | JooYeon Jhun |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-12f0c1e68ff8402e988176c517fd05e02023-12-03T13:24:49ZengMDPI AGCells2073-44092021-01-0110116210.3390/cells10010162GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg BalanceJooYeon Jhun0Jin Seok Woo1Seung Hoon Lee2Jeong-Hee Jeong3KyungAh Jung4Wonhee Hur5Seon-Yeong Lee6Jae Yoon Ryu7Young-Mee Moon8Yoon Ju Jung9Kyo Young Song10Kiyuk Chang11Seung Kew Yoon12Sung-Hwan Park13Mi-La Cho14The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, KoreaDivision of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USAThe Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, KoreaResearch Center, Impact Biotech, Seoul 137-040, KoreaThe Catholic University Liver Research Center & WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 137-040, KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, KoreaDivision of Gastrointestinal Surgery, Department of General Surgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 137-040, KoreaDivision of Gastrointestinal Surgery, Department of General Surgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 137-040, KoreaCardiovascular Center and Cardiology Division, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-040, KoreaThe Catholic University Liver Research Center & WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 137-040, KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, KoreaObesity, 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.https://www.mdpi.com/2073-4409/10/1/162obesityGRIM19STAT3Th17 |
spellingShingle | 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 GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance Cells obesity GRIM19 STAT3 Th17 |
title | GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance |
title_full | GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance |
title_fullStr | GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance |
title_full_unstemmed | GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance |
title_short | GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance |
title_sort | grim19 impedes obesity by regulating inflammatory white fat browning and promoting th17 treg balance |
topic | obesity GRIM19 STAT3 Th17 |
url | https://www.mdpi.com/2073-4409/10/1/162 |
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