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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/10/1/162
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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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