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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Zhang, Mengshu Zhao, Wanwan Zhang, Zhen He, Mengting Zhang, Ya Song, Bing Liu, Jinlei Zhang, Haoqiang |
| Abstract | Background Nonalcoholic fatty liver disease (NAFLD) shares common pathogenic mechanisms of type 2 diabetes mellitus (T2DM) with upregulated advanced glycation end products (AGEs). Here, we aim to investigate the effect of FPS-ZM1, an inhibitor for receptor for AGEs (RAGE), on lipid deposition in the liver of mice. Methods KK-Ay mice were used as models of T2DM with NAFLD, while C57BL/6j mice were controls. Additionally, KK-Ay mice were treated with DMSO (with a concentration of 1%), with or without FPS-ZM1 (3 mg/kg/day, i.p). Lipid deposition in hepatocytes was observed using oil red O stain. Levels of AGEs and RAGE were measured. Sterol regulatory element-binding protein-1c (SREBP-1c), as well as nuclear factor κB p65 (p65 nfκb) and mitogen-activated protein kinase p38 (p38 MAPK), were also detected. Results Lipid deposition is increased in the hepatocytes of KK-Ay mice compared to C57BL/6j mice. In addition, not only were the levels of AGEs elevated in plasma, but also the levels of RAGE in liver tissue. Although total SREBP-1c levels did not change in the liver of diabetic mice, mature SREBP-1c increased in KK-Ay mice with diabetes mellitus. Moreover, diabetic mice showed increased levels of phosphorylated-p65 nfκb (p-p65 nfκb) and phosphorylated-p38 MAPK (p-p38 MAPK). On the contrary, FPS-ZM1 decreased lipid deposition in liver cells, as well as mature SREBP-1c, p-p65 nfκb and p-p38 MAPK levels in liver tissue. Conclusion Generally, FPS-ZM1 may attenuate lipid deposition in hepatocytes of diabetic mice via SREBP-1c down-regulation. This may depend on the downregulation of p65 nfκb and p38 MAPK phosphorylation. |
| Related Links | https://bmcendocrdisord.biomedcentral.com/counter/pdf/10.1186/s12902-024-01705-2.pdf |
| Ending Page | 9 |
| Page Count | 9 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14726823 |
| DOI | 10.1186/s12902-024-01705-2 |
| Journal | BMC Endocrine Disorders |
| Issue Number | 1 |
| Volume Number | 24 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-08-29 |
| Access Restriction | Open |
| Subject Keyword | Endocrinology Metabolic Diseases Diabetes Andrology Nonalcoholic fatty liver Type 2 diabetes mellitus Advanced glycation end products Sterol regulatory element binding protein-1c |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism |
| Journal Impact Factor | 2.8/2023 |
| 5-Year Journal Impact Factor | 3.1/2023 |
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