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trans-Chalcone protects against high-fat diet-induced kidney injury in rats by regulating the miR-874/TLR4 pathway
Elham Karimi-Sales1,2, Khalil Hajiasgharzadeh1, Mohammad Reza Alipour3
1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
BackgroundChronic high-fat diet (HFD) consumption is linked to chronic kidney disease. Toll-like receptor 4 (TLR4) promotes pro-fibrotic and pro-inflammatory pathways in the kidney. It is directly inhibited by renal miR-874. trans-Chalcone has protective effects against HFD-related diseases. However, its effects on renal miR-874 and TLR4 expression in HFD-fed animals remain unexamined.AimThe current study examined the possible influences of trans-chalcone and HFD on the renal miR-874/TLR4 axis.MethodsMale rats were divided into control, HFD, and HFD + trans-chalcone groups. They received Tween 80 in control, high-fat emulsion in HFD and HFD + trans-chalcone groups, and trans-chalcone in the HFD + trans-chalcone group. Fasting insulin resistance index (FIRI) was calculated, and real-time PCR was used to determine the expression levels of miR-874 and TLR4 in the kidneys.ResultsChronic HFD feeding elevated FIRI levels. In contrast, co-treatment with trans-chalcone and HFD significantly reduced FIRI levels in the HFD + trans-chalcone group compared with the HFD group. Consumption of an HFD also significantly reduced miR-874 and increased TLR4 expression. These HFD-induced changes were inhibited by trans-chalcone. There were no significant differences in renal expression of miR-874 and TLR4 between the control and HFD + trans-chalcone groups.ConclusionDown-regulation of renal miR-874 may be responsible for elevated TLR4 mRNA levels during HFD feeding. Furthermore, miR-874 dysregulation may be linked to the development of HFD-related kidney disease. This study suggests that trans-chalcone is a potential therapeutic chalcone for protecting the kidney against the dysregulation of the miR-874/TLR4 pathway during HFD feeding.
Insights
Trans-chalcone protects kidneys from high-fat diet damage by restoring miR-874 and inhibiting TLR4. This study reveals trans-chalcone as a potential therapeutic for diet-induced kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Chronic high-fat diet (HFD) consumption is a known risk factor for chronic kidney disease.
- Toll-like receptor 4 (TLR4) exacerbates kidney injury by promoting pro-fibrotic and pro-inflammatory pathways.
- Renal miR-874 directly inhibits TLR4, suggesting a protective role in kidney health.
Purpose of the Study:
- To investigate the impact of trans-chalcone on the renal miR-874/TLR4 axis in rats fed a high-fat diet.
- To evaluate the therapeutic potential of trans-chalcone in mitigating HFD-induced kidney damage.
Main Methods:
- Male rats were assigned to control, HFD, or HFD + trans-chalcone groups.
- Fasting insulin resistance index (FIRI) was assessed.
- Real-time PCR quantified renal miR-874 and TLR4 expression levels.
Main Results:
- HFD feeding increased FIRI and decreased miR-874, while increasing TLR4 expression.
- Trans-chalcone co-treatment significantly reduced FIRI and reversed the HFD-induced changes in miR-874 and TLR4.
- No significant differences in miR-874 and TLR4 were observed between control and HFD + trans-chalcone groups.
Conclusions:
- Down-regulation of renal miR-874 may contribute to elevated TLR4 mRNA in HFD-induced kidney disease.
- miR-874 dysregulation is implicated in the pathogenesis of HFD-related kidney disease.
- Trans-chalcone demonstrates potential as a therapeutic agent for protecting kidneys via the miR-874/TLR4 pathway.
