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Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
A humanized osteopontin mouse model and its application in immunometabolic obesity studies
Nicole G Grün1, Karina Zeyda2, Veronica Moreno-Viedma1
1Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Abstract:
Osteopontin (OPN) is a multifunctional protein involved in several inflammatory processes and pathogeneses including obesity-related disorders and cancer. OPN binds to a variety of integrin receptors and CD44 resulting in a proinflammatory stimulus. Therefore, OPN constitutes a novel interesting target to develop new therapeutic strategies, which counteract OPN's proinflammatory properties. We established a humanized SPP1 (hSPP1) mouse model and evaluated its suitability as a model for obesity and insulin resistance. Unchallenged hSPP1 animals did not significantly differ in body weight and gross behavioral properties compared to wild-type (WT) animals. High-fat diet-challenged hSPP1 similarly developed obesity and inflammation, whereas insulin resistance was markedly changed. However, OPN expression profile in tissues was significantly altered in hSPP1 compared to WT depending on the diet. In conclusion, we developed a versatile humanized model to study the action of OPN in vivo and to develop strategies that target human OPN in a variety of pathologies.
Insights
Researchers developed a humanized SPP1 mouse model to study osteopontin (OPN) in obesity and inflammation. This model effectively mimics diet-induced obesity and inflammation, offering a new tool for therapeutic development targeting OPN.
Area of Science:
- Biochemistry
- Immunology
- Metabolic Diseases
Background:
- Osteopontin (OPN) is a key protein in inflammatory processes, implicated in obesity and cancer.
- OPN's pro-inflammatory effects are mediated through binding to integrin receptors and CD44.
- Targeting OPN offers a potential therapeutic strategy for inflammatory conditions.
Purpose of the Study:
- To establish and validate a humanized SPP1 (hSPP1) mouse model for studying OPN in vivo.
- To assess the model's utility in investigating obesity and insulin resistance.
- To explore OPN's role in diet-induced metabolic changes.
Main Methods:
- Generation of a humanized SPP1 (hSPP1) mouse model.
- Comparison of hSPP1 mice with wild-type (WT) littermates under standard and high-fat diet conditions.
- Analysis of body weight, behavioral properties, inflammation markers, and insulin resistance.
Main Results:
- hSPP1 mice showed no significant differences from WT mice without dietary challenge.
- High-fat diet induced obesity and inflammation in hSPP1 mice, with significant alterations in insulin resistance.
- Tissue OPN expression profiles were diet-dependently altered in hSPP1 compared to WT mice.
Conclusions:
- A versatile humanized SPP1 mouse model was successfully developed.
- This model is suitable for in vivo studies of OPN's function in various pathologies, including obesity and insulin resistance.
- The model facilitates the development of therapeutic strategies targeting human OPN.
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