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Long-Term High-Fat Diet Decreases Renal Insulin-Degrading Enzyme Expression and Function by Inhibiting the PPARγ
Qian Su1,2, Juan Huang2,3, Xi Chen2,3
1Department of Endocrinology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China.
Molecular Nutrition & Food Research
|February 2, 2023
Summary
High-fat diets induce insulin resistance by decreasing kidney insulin-degrading enzyme (IDE) activity. This involves the PPARγ pathway, and its activation can restore IDE function and improve insulin sensitivity.
Area of Science:
- Metabolic diseases
- Renal physiology
- Molecular endocrinology
Background:
- Long-term high-fat diet (HFD) is a key factor in obesity and type 2 diabetes, often linked to insulin resistance.
- Impaired insulin clearance contributes to insulin resistance, with the kidney playing a crucial role via the insulin-degrading enzyme (IDE).
Purpose of the Study:
- To investigate the role of renal insulin-degrading enzyme (IDE) in regulating insulin resistance in mice fed a high-fat diet (HFD).
Main Methods:
- Mice were fed an HFD for 24 weeks to induce obesity and insulin resistance.
- Insulin clearance, renal IDE expression and activity, and PPAR pathway involvement were assessed.
- In vitro studies used HK-2 cells treated with palmitic acid and rosiglitazone to examine IDE regulation.
Main Results:
- HFD led to insulin resistance, impaired insulin clearance, and reduced renal IDE expression and activity.
- Palmitic acid decreased IDE expression in HK-2 cells, an effect blocked by the PPARγ agonist rosiglitazone.
- HFD reduced renal PPARγ expression; rosiglitazone treatment improved insulin clearance and insulin resistance in HFD-fed mice.
Conclusions:
- Long-term HFD diminishes renal IDE expression and activity, contributing to insulin resistance.
- The PPARγ pathway is implicated in HFD-induced downregulation of renal IDE.
- Targeting PPARγ may offer a therapeutic strategy for improving insulin sensitivity in metabolic disorders.
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