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Dehydrozingerone inhibits renal lipotoxicity in high-fat diet-induced obese mice
Eun Soo Lee1,2, Jeong Suk Kang3,4, Hong Min Kim5
1Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
Abstract:
Ectopic fat accumulation in the kidneys causes oxidative stress, inflammation and cell death. Dehydrozingerone (DHZ) is a curcumin analog that exhibits antitumour, antioxidant and antidiabetic effects. However, the efficacy of DHZ in diabetic nephropathy (DN) is unknown. Here, we verified the efficacy of DHZ on DN. We divided the experimental animals into three groups: regular diet, 60% high-fat diet (HFD) and HFD with DHZ for 12 weeks. We analysed levels of renal triglycerides and urinary albumin and albumin-creatinine ratio, renal morphological changes and molecular changes via real-time polymerase chain reaction and immunoblotting. Furthermore, high glucose (HG)- or palmitate (PA)-stimulated mouse mesangial cells or mouse podocytes were treated with DHZ for 24 h. As a result, DHZ markedly reduced renal glycerol accumulation and albuminuria excretion through improvement of thickened glomerular basement membrane, podocyte loss and slit diaphragm reduction. In the renal cortex in the HFD group, phospho-AMPK and nephrin expression reduced, whereas arginase 2 and CD68 expression increased; however, these changes were recovered after DHZ administration. Increased reactive oxygen species (ROS) stimulated by HG or PA in podocytes was inhibited by DHZ treatment. Collectively, these findings indicate that DHZ ameliorates DN via inhibits of lipotoxicity-induced inflammation and ROS formation.
Insights
Dehydrozingerone (DHZ) effectively treats diabetic nephropathy (DN) by reducing kidney fat, inflammation, and oxidative stress. This curcumin analog protects kidney cells from damage caused by high fat diets and glucose.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Ectopic kidney fat accumulation triggers oxidative stress, inflammation, and cell death, contributing to diabetic nephropathy (DN).
- Dehydrozingerone (DHZ), a curcumin analog, possesses known anti-tumor, antioxidant, and anti-diabetic properties.
- The therapeutic potential of DHZ in managing DN remains unexplored.
Purpose of the Study:
- To investigate the efficacy of Dehydrozingerone (DHZ) in ameliorating diabetic nephropathy (DN).
- To elucidate the underlying mechanisms by which DHZ exerts its protective effects against DN.
Main Methods:
- Animal models were subjected to a high-fat diet (HFD) with or without DHZ for 12 weeks.
- Renal function was assessed by measuring triglyceride levels, albuminuria, and albumin-creatinine ratio.
- Molecular analyses included gene and protein expression studies (RT-PCR, immunoblotting) and assessment of reactive oxygen species (ROS) in kidney cells.
Main Results:
- DHZ treatment significantly reduced renal glycerol accumulation and albuminuria, improving glomerular basement membrane thickness, podocyte loss, and slit diaphragm integrity.
- DHZ administration reversed HFD-induced changes in renal cortex, including reduced phospho-AMPK and nephrin expression, and increased arginase 2 and CD68 expression.
- DHZ inhibited high glucose (HG)- or palmitate (PA)-induced ROS production in mouse podocytes and mesangial cells.
Conclusions:
- Dehydrozingerone (DHZ) demonstrates significant therapeutic potential in ameliorating diabetic nephropathy (DN).
- DHZ mitigates DN by inhibiting lipotoxicity-induced inflammation and oxidative stress, particularly ROS formation.
- DHZ offers a promising therapeutic strategy for managing kidney complications associated with diabetes.
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