Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling
Summary: Adipose tissue remodels via hypertrophy or hyperplasia in response to nutrient status, but the mechanisms governing these expansion modes remain unclear. Here, we identify a nutrient-sensitive epigenetic circuit linking glucose metabolism to chromatin remodeling during adipogenesis. Upon gl...
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2025-08-01
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| author | Chenxu Yang Makoto Arai Eko Fuji Ariyanto Ji Zhang Debby Mirani Lubis Ryo Ito Shiyu Xie Mio Nitta Fuka Kawashima Tomofumi Ishitsuka Chaoran Yang Tomohiro Suzuki Tetsuro Komatsu Hina Sagae Hitomi Jin Hiroki Takahashi Eri Kobayashi Yuchen Wei Bohao Liu Hyunmi Choi Youichiro Wada Toshiya Tanaka Tsuyoshi Osawa Hiroshi Kimura Tatsuhiko Kodama Hiroyuki Aburatani Makoto Tachibana Yoichi Shinkai Takeshi Inagaki Tomoyoshi Soga Timothy F. Osborne Takeshi Yoneshiro Yoshihiro Matsumura Juro Sakai |
| author_facet | Chenxu Yang Makoto Arai Eko Fuji Ariyanto Ji Zhang Debby Mirani Lubis Ryo Ito Shiyu Xie Mio Nitta Fuka Kawashima Tomofumi Ishitsuka Chaoran Yang Tomohiro Suzuki Tetsuro Komatsu Hina Sagae Hitomi Jin Hiroki Takahashi Eri Kobayashi Yuchen Wei Bohao Liu Hyunmi Choi Youichiro Wada Toshiya Tanaka Tsuyoshi Osawa Hiroshi Kimura Tatsuhiko Kodama Hiroyuki Aburatani Makoto Tachibana Yoichi Shinkai Takeshi Inagaki Tomoyoshi Soga Timothy F. Osborne Takeshi Yoneshiro Yoshihiro Matsumura Juro Sakai |
| author_sort | Chenxu Yang |
| collection | DOAJ |
| description | Summary: Adipose tissue remodels via hypertrophy or hyperplasia in response to nutrient status, but the mechanisms governing these expansion modes remain unclear. Here, we identify a nutrient-sensitive epigenetic circuit linking glucose metabolism to chromatin remodeling during adipogenesis. Upon glucose stimulation, α-ketoglutarate (α-KG) accumulates in the nucleus and activates the histone demethylase JMJD1A to remove repressive histone H3 lysine 9 dimethylation (H3K9me2) marks at glycolytic and adipogenic gene loci, including Pparg. JMJD1A is recruited to pre-marked promoter chromatin via nuclear factor IC (NFIC), enabling carbohydrate-responsive element-binding protein (ChREBP) binding and transcriptional activation. This feedforward mechanism couples nutrient flux to chromatin accessibility and gene expression. In vivo, JMJD1A is essential for de novo adipogenesis and hyperplastic expansion in visceral fat under nutrient excess. JMJD1A deficiency impairs hyperplasia, exacerbates adipocyte hypertrophy, and induces local inflammation. These findings define a glucose-α-KG-JMJD1A-ChREBP axis regulating depot-specific adipogenesis and uncover a chromatin-based mechanism by which glucose metabolism governs adaptive adipose tissue remodeling. |
| format | Article |
| id | doaj-art-8a7cc2c0164e40c48aaae429546f1f0a |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| series | Cell Reports |
| spelling | doaj-art-8a7cc2c0164e40c48aaae429546f1f0a2025-08-20T03:34:29ZengElsevierCell Reports2211-12472025-08-0144811606010.1016/j.celrep.2025.116060Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodelingChenxu Yang0Makoto Arai1Eko Fuji Ariyanto2Ji Zhang3Debby Mirani Lubis4Ryo Ito5Shiyu Xie6Mio Nitta7Fuka Kawashima8Tomofumi Ishitsuka9Chaoran Yang10Tomohiro Suzuki11Tetsuro Komatsu12Hina Sagae13Hitomi Jin14Hiroki Takahashi15Eri Kobayashi16Yuchen Wei17Bohao Liu18Hyunmi Choi19Youichiro Wada20Toshiya Tanaka21Tsuyoshi Osawa22Hiroshi Kimura23Tatsuhiko Kodama24Hiroyuki Aburatani25Makoto Tachibana26Yoichi Shinkai27Takeshi Inagaki28Tomoyoshi Soga29Timothy F. Osborne30Takeshi Yoneshiro31Yoshihiro Matsumura32Juro Sakai33Division of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan; Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang 45363, IndonesiaDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanLaboratory of Epigenetics and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, JapanLaboratory of Epigenetics and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanIsotope Science Center, The University of Tokyo, Tokyo 113-0032, JapanLaboratory for Systems Biology, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, JapanDivision of Nutriomics and Oncology, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, JapanCell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, JapanLaboratory for Systems Biology, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, JapanGenome Science and Medicine Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, JapanLaboratory of Epigenome Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, JapanCellular Memory Laboratory, RIKEN Cluster for Pioneering Research, Wako 351-0198, JapanLaboratory of Epigenetics and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo 108-8345, JapanDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, and Medicine in the Division of Endocrinology, Diabetes and Metabolism of the Johns Hopkins University School of Medicine, Petersburg, FL, USADivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development (AMED), Tokyo, Japan; Corresponding authorDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development (AMED), Tokyo, Japan; Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, Akita 010-8543, Japan; Corresponding authorDivision of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development (AMED), Tokyo, Japan; Corresponding authorSummary: Adipose tissue remodels via hypertrophy or hyperplasia in response to nutrient status, but the mechanisms governing these expansion modes remain unclear. Here, we identify a nutrient-sensitive epigenetic circuit linking glucose metabolism to chromatin remodeling during adipogenesis. Upon glucose stimulation, α-ketoglutarate (α-KG) accumulates in the nucleus and activates the histone demethylase JMJD1A to remove repressive histone H3 lysine 9 dimethylation (H3K9me2) marks at glycolytic and adipogenic gene loci, including Pparg. JMJD1A is recruited to pre-marked promoter chromatin via nuclear factor IC (NFIC), enabling carbohydrate-responsive element-binding protein (ChREBP) binding and transcriptional activation. This feedforward mechanism couples nutrient flux to chromatin accessibility and gene expression. In vivo, JMJD1A is essential for de novo adipogenesis and hyperplastic expansion in visceral fat under nutrient excess. JMJD1A deficiency impairs hyperplasia, exacerbates adipocyte hypertrophy, and induces local inflammation. These findings define a glucose-α-KG-JMJD1A-ChREBP axis regulating depot-specific adipogenesis and uncover a chromatin-based mechanism by which glucose metabolism governs adaptive adipose tissue remodeling.http://www.sciencedirect.com/science/article/pii/S2211124725008319CP: Metabolism |
| spellingShingle | Chenxu Yang Makoto Arai Eko Fuji Ariyanto Ji Zhang Debby Mirani Lubis Ryo Ito Shiyu Xie Mio Nitta Fuka Kawashima Tomofumi Ishitsuka Chaoran Yang Tomohiro Suzuki Tetsuro Komatsu Hina Sagae Hitomi Jin Hiroki Takahashi Eri Kobayashi Yuchen Wei Bohao Liu Hyunmi Choi Youichiro Wada Toshiya Tanaka Tsuyoshi Osawa Hiroshi Kimura Tatsuhiko Kodama Hiroyuki Aburatani Makoto Tachibana Yoichi Shinkai Takeshi Inagaki Tomoyoshi Soga Timothy F. Osborne Takeshi Yoneshiro Yoshihiro Matsumura Juro Sakai Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling Cell Reports CP: Metabolism |
| title | Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling |
| title_full | Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling |
| title_fullStr | Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling |
| title_full_unstemmed | Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling |
| title_short | Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling |
| title_sort | glucose activated jmjd1a drives visceral adipogenesis via α ketoglutarate dependent chromatin remodeling |
| topic | CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725008319 |
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