Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia
Abstract
:1. Introduction
2. Lipotoxicity and DKD
2.1. Lipid Metabolism—Physiologic Versus DKD
2.1.1. Fatty Acid (FA) (Figure 1)
FA Uptake—Normal and DKD Patients
FA Synthesis
FA Oxidation (FAO)
FA-Induced Post-Translational Modifications (PTMs)
2.1.2. Cholesterol (Figure 2)
Cholesterol Uptake, Synthesis, and Efflux
2.2. Lipid-Induced Oxidative Stress in Lipid-Rich Kidney Disease, Including DKD
3. Hypoxia and DKD
3.1. Increased Risk of Hypoxic Injury in Kidney
3.2. Renal Hypoxia and Oxidative Stress in DKD
3.3. HIF-1 Activation in Hypoxia: A Double-Edged Sword
4. Oxidative Stress and DKD
4.1. The Role of ROS and Oxidative Stress in DKD
4.2. ROS, Oxidative Stress, and Intracellular Signaling Pathways
4.2.1. Keap1-Nrf2 Pathway
4.2.2. Forkhead Box O (FoxO) Proteins
4.2.3. Nuclear Factor (NF)-κB Pathway
4.3. ROS, Oxidative Stress, and Cellular Organelles in the Context of DKD
4.3.1. Mitochondria
4.3.2. ER and Peroxisome
4.3.3. Mitochondria-Associated ER Membrane (MAM)
5. Therapeutic Approaches to Modify DKD
5.1. Antilipidemic Drug
5.1.1. Statins/Fenofibrate
5.1.2. Ezetimibe
5.1.3. PCSK9 Inhibitors
5.1.4. ABCA1 Inducer
5.2. SGLT2 Inhibitor/GLP-1 Agonist
5.2.1. SGLT2 Inhibitor
5.2.2. GLP-1 Agonist
5.3. NRF2 Activators
5.3.1. Bardoxolone Methyl
5.3.2. Curcumin
5.3.3. Sulforaphane
5.4. Resveratrol
5.5. Vitamin D
5.6. Adiponectin Receptor Activator
5.7. HIF-1 Stabilizer (Prolyl Hydroxylase Inhibitor)
5.8. Potential Concerns in Applying Anti-Oxidants for Treating DKD
6. Conclusions and Perspectives
Type | Model | Advantages | Limitations | Reference Numbers in This Review |
---|---|---|---|---|
Type 1 DM | STZ |
|
| [49] |
Unilateral nephrectomy + STZ |
|
| [45] | |
Alloxan |
|
| [76] | |
Type 1 DM (Auto-immune) | NOD |
|
| [50] |
Type 2 DM | db/db |
|
| [19,23,46,49,57,63,120,128,129,157,193,200] |
ob/ob |
|
| [49,164] | |
HFD |
|
| [55,61,156,158,159,186] | |
HFD + STZ |
|
| [64] | |
HFD + ApoE−/− |
|
| [169] | |
ZDF |
|
| [75] |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Chae, S.Y.; Kim, Y.; Park, C.W. Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia. Antioxidants 2023, 12, 2083. https://doi.org/10.3390/antiox12122083
Chae SY, Kim Y, Park CW. Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia. Antioxidants. 2023; 12(12):2083. https://doi.org/10.3390/antiox12122083
Chicago/Turabian StyleChae, Seung Yun, Yaeni Kim, and Cheol Whee Park. 2023. "Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia" Antioxidants 12, no. 12: 2083. https://doi.org/10.3390/antiox12122083
APA StyleChae, S. Y., Kim, Y., & Park, C. W. (2023). Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia. Antioxidants, 12(12), 2083. https://doi.org/10.3390/antiox12122083