The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress
Animal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperg...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/1214 |
| _version_ | 1797339732629258240 |
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| author | Sai Pranathi Meda Venkata Hainan Li Liping Xu Jie-Mei Wang |
| author_facet | Sai Pranathi Meda Venkata Hainan Li Liping Xu Jie-Mei Wang |
| author_sort | Sai Pranathi Meda Venkata |
| collection | DOAJ |
| description | Animal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, blood glucose and lipid profiles were measured. The high-fat (HF) diet damaged insulin sensitivity and increased triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and liver lipid deposition. STZ increased blood glucose and liver fibrosis with less effects on blood lipids or liver lipid deposition. The combination of DIO and STZ treatments led to significant liver lipid deposition and fibrosis. Female mice showed delayed body weight gain on HF diet and resisted STZ-induced hyperglycemia. However, once they developed DIO, which occurs around 26 weeks of HF diet, the female mice were prone to STZ-induced hyperglycemia. In hindlimb ischemia, male mice in the DIO-STZ group showed significantly worse neovascularization compared with DIO or STZ groups. The DIO-STZ females showed significantly worse recovery than the DIO-STZ males. Our observations suggest that DIO-STZ is a plausible model for studying metabolic and cardiovascular disorders in obesity and diabetes. Moreover, the findings in female animals stress the need to assess sexual dimorphism and investigate the underlying mechanisms that contribute to the worse vasculopathy manifestations in females in metabolic models. |
| first_indexed | 2024-03-08T09:52:37Z |
| format | Article |
| id | doaj.art-29427383d3dc452ba0d97b798d47963b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:52:37Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-29427383d3dc452ba0d97b798d47963b2024-01-29T13:58:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01252121410.3390/ijms25021214The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic StressSai Pranathi Meda Venkata0Hainan Li1Liping Xu2Jie-Mei Wang3Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, 3122 Applebaum Building, Detroit, MI 48201, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, 3122 Applebaum Building, Detroit, MI 48201, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, 3122 Applebaum Building, Detroit, MI 48201, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, 3122 Applebaum Building, Detroit, MI 48201, USAAnimal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, blood glucose and lipid profiles were measured. The high-fat (HF) diet damaged insulin sensitivity and increased triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and liver lipid deposition. STZ increased blood glucose and liver fibrosis with less effects on blood lipids or liver lipid deposition. The combination of DIO and STZ treatments led to significant liver lipid deposition and fibrosis. Female mice showed delayed body weight gain on HF diet and resisted STZ-induced hyperglycemia. However, once they developed DIO, which occurs around 26 weeks of HF diet, the female mice were prone to STZ-induced hyperglycemia. In hindlimb ischemia, male mice in the DIO-STZ group showed significantly worse neovascularization compared with DIO or STZ groups. The DIO-STZ females showed significantly worse recovery than the DIO-STZ males. Our observations suggest that DIO-STZ is a plausible model for studying metabolic and cardiovascular disorders in obesity and diabetes. Moreover, the findings in female animals stress the need to assess sexual dimorphism and investigate the underlying mechanisms that contribute to the worse vasculopathy manifestations in females in metabolic models.https://www.mdpi.com/1422-0067/25/2/1214hyperglycemiadyslipidemiaanimal modelneovascularizationsexual dimorphism |
| spellingShingle | Sai Pranathi Meda Venkata Hainan Li Liping Xu Jie-Mei Wang The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress International Journal of Molecular Sciences hyperglycemia dyslipidemia animal model neovascularization sexual dimorphism |
| title | The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress |
| title_full | The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress |
| title_fullStr | The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress |
| title_full_unstemmed | The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress |
| title_short | The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress |
| title_sort | impact of obesity on diabetes onset and neovascularization in mouse models of metabolic stress |
| topic | hyperglycemia dyslipidemia animal model neovascularization sexual dimorphism |
| url | https://www.mdpi.com/1422-0067/25/2/1214 |
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