Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1
Background: Hypothalamic neuroinflammation is associated with disorders of lipid metabolism. Considering the anti-neuroinflammation effects of sodium-glucose cotransporter 2(SGLT2) inhibitors, a central administration of Dapagliflozin is postulated to provide hypothalamic protection and change lipid...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223016384 |
| _version_ | 1797630580133724160 |
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| author | Jingjing Da Yongjie Xu Ying Tan Jiqin Zhang Jiali Yu Jianqiu Zhao Qingen Da Fuxun Yu Yan Zha |
| author_facet | Jingjing Da Yongjie Xu Ying Tan Jiqin Zhang Jiali Yu Jianqiu Zhao Qingen Da Fuxun Yu Yan Zha |
| author_sort | Jingjing Da |
| collection | DOAJ |
| description | Background: Hypothalamic neuroinflammation is associated with disorders of lipid metabolism. Considering the anti-neuroinflammation effects of sodium-glucose cotransporter 2(SGLT2) inhibitors, a central administration of Dapagliflozin is postulated to provide hypothalamic protection and change lipid metabolism in kidney against diabetic kidney disease (DKD). Methods: Blood samples of DKD patients were collected. Male Sprague-Dawley (SD) rats with 30 mg/kg streptozotocin and a high-fat diet, db/db mice and palmitic acid (PA)-stimulated BV2 microglia were used for study models. 0.28 mg/3ul dapagliflozin was injected into the lateral ventricle in db/db mice. Genes and protein expression levels were determined by qPCR, western blotting, immunofluorescence, and immunohistochemistry staining. Secreted IL-1β and IL-6 were quantified by ELISA. Oil red O staining, lipidomic, and non-targeted metabolomics were performed to evaluate abnormal lipid metabolism in kidney. Results: The decrease of serum MCPIP1 was an independent risk factor for renal progression in DKD patients (OR=1.22, 95 %CI: 1.02–1.45, P = 0.033). Higher microglia marker IBA1 and lower MCPIP1 in the hypothalamus, as well as lipid droplet deposition increasing in the kidney were observed in DKD rats. Central dapagliflozin could reduce the blood sugar, hypothalamic inflammatory cytokines, lipid droplet deposition in renal tubular. Lipidomics and metabolomics results showed that dapagliflozin changed 37 lipids and 19 metabolites considered on promoting lipolysis. These lipid metabolism changes were attributed to dapagliflozin by upregulating MCPIP1, and inhibiting cytokines in the microglia induced by PA. Conclusions: Central administrated Dapagliflozin elicits an anti-inflammatory effect by upregulating MCPIP1 levels in microglia and changes lipid metabolism in kidney of DKD. |
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| format | Article |
| id | doaj.art-231adfb528c14a7cb63ddec52c1fdf88 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T11:10:10Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-231adfb528c14a7cb63ddec52c1fdf882023-11-12T04:39:30ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01168115840Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1Jingjing Da0Yongjie Xu1Ying Tan2Jiqin Zhang3Jiali Yu4Jianqiu Zhao5Qingen Da6Fuxun Yu7Yan Zha8Renal Division, Department of Medicine, Guizhou Provincial People’s Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guiyang, Guizhou 550002, China; NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Laboratory Medicine, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, ChinaDepartment of Neurosurgery, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, ChinaRenal Division, Department of Medicine, Guizhou Provincial People’s Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guiyang, Guizhou 550002, China; NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaRenal Division, Department of Medicine, Guizhou Provincial People’s Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guiyang, Guizhou 550002, China; NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, ChinaNHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaRenal Division, Department of Medicine, Guizhou Provincial People’s Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guiyang, Guizhou 550002, China; NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial People’s Hospital, Guiyang, China; Correspondence to: Renal Division, Department of Medicine, Guizhou Provincial People’s Hospital, NO. 83, Zhongshan Road, Yunyan District, Guiyang, Guizhou, China.Background: Hypothalamic neuroinflammation is associated with disorders of lipid metabolism. Considering the anti-neuroinflammation effects of sodium-glucose cotransporter 2(SGLT2) inhibitors, a central administration of Dapagliflozin is postulated to provide hypothalamic protection and change lipid metabolism in kidney against diabetic kidney disease (DKD). Methods: Blood samples of DKD patients were collected. Male Sprague-Dawley (SD) rats with 30 mg/kg streptozotocin and a high-fat diet, db/db mice and palmitic acid (PA)-stimulated BV2 microglia were used for study models. 0.28 mg/3ul dapagliflozin was injected into the lateral ventricle in db/db mice. Genes and protein expression levels were determined by qPCR, western blotting, immunofluorescence, and immunohistochemistry staining. Secreted IL-1β and IL-6 were quantified by ELISA. Oil red O staining, lipidomic, and non-targeted metabolomics were performed to evaluate abnormal lipid metabolism in kidney. Results: The decrease of serum MCPIP1 was an independent risk factor for renal progression in DKD patients (OR=1.22, 95 %CI: 1.02–1.45, P = 0.033). Higher microglia marker IBA1 and lower MCPIP1 in the hypothalamus, as well as lipid droplet deposition increasing in the kidney were observed in DKD rats. Central dapagliflozin could reduce the blood sugar, hypothalamic inflammatory cytokines, lipid droplet deposition in renal tubular. Lipidomics and metabolomics results showed that dapagliflozin changed 37 lipids and 19 metabolites considered on promoting lipolysis. These lipid metabolism changes were attributed to dapagliflozin by upregulating MCPIP1, and inhibiting cytokines in the microglia induced by PA. Conclusions: Central administrated Dapagliflozin elicits an anti-inflammatory effect by upregulating MCPIP1 levels in microglia and changes lipid metabolism in kidney of DKD.http://www.sciencedirect.com/science/article/pii/S0753332223016384Diabetic nephropathyHypothalamic inflammationRenal lipid metabolismMonocyte chemoattractant protein-induced protein 1Sodium-glucose cotransporter 2 |
| spellingShingle | Jingjing Da Yongjie Xu Ying Tan Jiqin Zhang Jiali Yu Jianqiu Zhao Qingen Da Fuxun Yu Yan Zha Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1 Biomedicine & Pharmacotherapy Diabetic nephropathy Hypothalamic inflammation Renal lipid metabolism Monocyte chemoattractant protein-induced protein 1 Sodium-glucose cotransporter 2 |
| title | Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1 |
| title_full | Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1 |
| title_fullStr | Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1 |
| title_full_unstemmed | Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1 |
| title_short | Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1 |
| title_sort | central administration of dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating mcpip1 |
| topic | Diabetic nephropathy Hypothalamic inflammation Renal lipid metabolism Monocyte chemoattractant protein-induced protein 1 Sodium-glucose cotransporter 2 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223016384 |
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