Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet–Induced Obesity in Mice
Calcium signaling contributes to obesity and its related disorders, such as diabetes. We herein investigated the effects of calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors on diet-induced obesity in mice. In mice fed a high-fat diet (HFD), the administration of the CaMKII inhibito...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Journal of Obesity |
| Online Access: | http://dx.doi.org/10.1155/jobe/5530467 |
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| author | Naoyuki Kawao Ryosuke Satoh Yuya Mizukami Katsumi Okumoto Genzoh Tanabe Osamu Muraoka Reiko Sugiura Hiroshi Kaji |
| author_facet | Naoyuki Kawao Ryosuke Satoh Yuya Mizukami Katsumi Okumoto Genzoh Tanabe Osamu Muraoka Reiko Sugiura Hiroshi Kaji |
| author_sort | Naoyuki Kawao |
| collection | DOAJ |
| description | Calcium signaling contributes to obesity and its related disorders, such as diabetes. We herein investigated the effects of calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors on diet-induced obesity in mice. In mice fed a high-fat diet (HFD), the administration of the CaMKII inhibitor KN-93 and the glycolipid acremomannolipin A with the suppression of CaMKII phosphorylation reduced fat mass in the whole body, epididymal and subcutaneous white adipose tissue weights, and lipid accumulation in epididymal and subcutaneous white adipose tissues, but not muscle mass or bone mineral density at the tibia. Moreover, the administration of KN-93 and acremomannolipin A improved glucose intolerance in HFD-fed mice. In an in vitro study on preadipocytic 3T3-L1 cells and mouse adipose tissue-derived stromal cells, KN-93 and acremomannolipin A suppressed adipogenic differentiation, proliferation, and lipid accumulation. In conclusion, this is the first study to demonstrate that CaMKII inhibitors mitigated the development of diet-induced obesity in mice partly through the suppression of adipogenic differentiation, cell proliferation, and lipid accumulation in adipocytes. Inhibiting CaMKII could be a potential strategy for obesity treatment. |
| format | Article |
| id | doaj-art-15c7bd2a2d154d5a896baecb3318c4ad |
| institution | DOAJ |
| issn | 2090-0716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Obesity |
| spelling | doaj-art-15c7bd2a2d154d5a896baecb3318c4ad2025-08-20T03:12:27ZengWileyJournal of Obesity2090-07162025-01-01202510.1155/jobe/5530467Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet–Induced Obesity in MiceNaoyuki Kawao0Ryosuke Satoh1Yuya Mizukami2Katsumi Okumoto3Genzoh Tanabe4Osamu Muraoka5Reiko Sugiura6Hiroshi Kaji7Department of Physiology and Regenerative MedicineLaboratory of Molecular PharmacogenomicsDepartment of Physiology and Regenerative MedicineLife Science Research InstituteLaboratory of Organic ChemistryPharmaceutical Research and Technology InstituteLaboratory of Molecular PharmacogenomicsDepartment of Physiology and Regenerative MedicineCalcium signaling contributes to obesity and its related disorders, such as diabetes. We herein investigated the effects of calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors on diet-induced obesity in mice. In mice fed a high-fat diet (HFD), the administration of the CaMKII inhibitor KN-93 and the glycolipid acremomannolipin A with the suppression of CaMKII phosphorylation reduced fat mass in the whole body, epididymal and subcutaneous white adipose tissue weights, and lipid accumulation in epididymal and subcutaneous white adipose tissues, but not muscle mass or bone mineral density at the tibia. Moreover, the administration of KN-93 and acremomannolipin A improved glucose intolerance in HFD-fed mice. In an in vitro study on preadipocytic 3T3-L1 cells and mouse adipose tissue-derived stromal cells, KN-93 and acremomannolipin A suppressed adipogenic differentiation, proliferation, and lipid accumulation. In conclusion, this is the first study to demonstrate that CaMKII inhibitors mitigated the development of diet-induced obesity in mice partly through the suppression of adipogenic differentiation, cell proliferation, and lipid accumulation in adipocytes. Inhibiting CaMKII could be a potential strategy for obesity treatment.http://dx.doi.org/10.1155/jobe/5530467 |
| spellingShingle | Naoyuki Kawao Ryosuke Satoh Yuya Mizukami Katsumi Okumoto Genzoh Tanabe Osamu Muraoka Reiko Sugiura Hiroshi Kaji Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet–Induced Obesity in Mice Journal of Obesity |
| title | Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet–Induced Obesity in Mice |
| title_full | Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet–Induced Obesity in Mice |
| title_fullStr | Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet–Induced Obesity in Mice |
| title_full_unstemmed | Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet–Induced Obesity in Mice |
| title_short | Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet–Induced Obesity in Mice |
| title_sort | calcium calmodulin dependent protein kinase ii inhibitors mitigate high fat diet induced obesity in mice |
| url | http://dx.doi.org/10.1155/jobe/5530467 |
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