Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism
Summary: The transcription factor carbohydrate response element binding protein (ChREBP) activates genes of glucose, fructose, and lipid metabolism in response to carbohydrate feeding. Integrated transcriptomic and metabolomic analyses in rats with GalNac-siRNA-mediated suppression of ChREBP express...
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472500049X |
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| author | Jie An Inna Astapova Guofang Zhang Andrew L. Cangelosi Olga Ilkayeva Hannah Marchuk Michael J. Muehlbauer Tabitha George Joseph Brozinick Mark A. Herman Christopher B. Newgard |
| author_facet | Jie An Inna Astapova Guofang Zhang Andrew L. Cangelosi Olga Ilkayeva Hannah Marchuk Michael J. Muehlbauer Tabitha George Joseph Brozinick Mark A. Herman Christopher B. Newgard |
| author_sort | Jie An |
| collection | DOAJ |
| description | Summary: The transcription factor carbohydrate response element binding protein (ChREBP) activates genes of glucose, fructose, and lipid metabolism in response to carbohydrate feeding. Integrated transcriptomic and metabolomic analyses in rats with GalNac-siRNA-mediated suppression of ChREBP expression in liver reveal other ChREBP functions. GalNac-siChREBP treatment reduces expression of genes involved in coenzyme A (CoA) biosynthesis, with lowering of CoA and short-chain acyl-CoA levels. Despite suppression of pyruvate kinase, pyruvate levels are maintained, possibly via increased expression of pyruvate and amino acid transporters. In addition, expression of multiple anaplerotic enzymes is decreased by GalNac-siChREBP treatment, affecting TCA cycle intermediates. Finally, GalNAc-siChREBP treatment suppresses late steps in purine and NAD synthesis, with increases in precursors and lowering of end products in both pathways. In sum, our study reveals functions of ChREBP beyond its canonical roles in carbohydrate and lipid metabolism to include regulation of substrate transport, mitochondrial function, and energy balance. |
| format | Article |
| id | doaj-art-30e8b173602b493996f689f446c1fb64 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-30e8b173602b493996f689f446c1fb642025-02-09T05:00:04ZengElsevierCell Reports2211-12472025-02-01442115278Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolismJie An0Inna Astapova1Guofang Zhang2Andrew L. Cangelosi3Olga Ilkayeva4Hannah Marchuk5Michael J. Muehlbauer6Tabitha George7Joseph Brozinick8Mark A. Herman9Christopher B. Newgard10Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USASarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA; Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Duke University Medical Center, Durham, NC, USASarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USASarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA; Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Duke University Medical Center, Durham, NC, USASarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USASarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USASarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USAEli Lilly Research Laboratories, Indianapolis, IN, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USASarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA; Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC, USA; Corresponding authorSummary: The transcription factor carbohydrate response element binding protein (ChREBP) activates genes of glucose, fructose, and lipid metabolism in response to carbohydrate feeding. Integrated transcriptomic and metabolomic analyses in rats with GalNac-siRNA-mediated suppression of ChREBP expression in liver reveal other ChREBP functions. GalNac-siChREBP treatment reduces expression of genes involved in coenzyme A (CoA) biosynthesis, with lowering of CoA and short-chain acyl-CoA levels. Despite suppression of pyruvate kinase, pyruvate levels are maintained, possibly via increased expression of pyruvate and amino acid transporters. In addition, expression of multiple anaplerotic enzymes is decreased by GalNac-siChREBP treatment, affecting TCA cycle intermediates. Finally, GalNAc-siChREBP treatment suppresses late steps in purine and NAD synthesis, with increases in precursors and lowering of end products in both pathways. In sum, our study reveals functions of ChREBP beyond its canonical roles in carbohydrate and lipid metabolism to include regulation of substrate transport, mitochondrial function, and energy balance.http://www.sciencedirect.com/science/article/pii/S221112472500049XCP: Metabolism |
| spellingShingle | Jie An Inna Astapova Guofang Zhang Andrew L. Cangelosi Olga Ilkayeva Hannah Marchuk Michael J. Muehlbauer Tabitha George Joseph Brozinick Mark A. Herman Christopher B. Newgard Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism Cell Reports CP: Metabolism |
| title | Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism |
| title_full | Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism |
| title_fullStr | Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism |
| title_full_unstemmed | Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism |
| title_short | Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism |
| title_sort | integration of metabolomic and transcriptomic analyses reveals regulatory functions of the chrebp transcription factor in energy metabolism |
| topic | CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S221112472500049X |
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