Resveratrol prevents renal lipotoxicity in high-fat diet-treated mouse model through regulating PPAR-α pathway

Area of Science:

• Nephrology
• Metabolic Diseases
• Pharmacology

Background:

• Obesity-related kidney disease is a growing health concern.
• The mechanisms underlying resveratrol's (RSV) renoprotective effects are not fully understood.
• Investigating RSV's impact on high-fat diet-induced renal damage is crucial.

Purpose of the Study:

• To investigate the renoprotective effects of resveratrol (RSV) in a mouse model of obesity-related kidney disease.
• To elucidate the underlying molecular mechanisms, particularly focusing on lipid metabolism and inflammatory pathways.
• To assess RSV's efficacy in mitigating structural and functional renal damage induced by a high-fat diet (HFD).

Main Methods:

• Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks, with or without 400 mg/kg RSV treatment.
• Renal structure, function, and biochemical markers were assessed.
• Gene and protein expression related to inflammation, oxidative stress, and lipid metabolism were analyzed, including key targets like PPAR-α and AMPK.

Main Results:

• RSV treatment significantly reduced glomerular volume, renal glycogen, and collagen deposition in HFD-fed mice.
• RSV attenuated renal dysfunction, evidenced by decreased blood urea nitrogen and microalbuminuria.
• RSV markedly reduced inflammatory markers (TNF-α, IL-6, iNOS), oxidative stress (4-HNE), and lipid accumulation.
• RSV enhanced the expression of lipolytic genes (PPAR-α, CPT-1, MCAD) and increased PPAR-α protein and AMPK phosphorylation, without affecting lipogenic genes.

Conclusions:

• Resveratrol exerts significant renoprotective effects against high-fat diet-induced renal damage.
• RSV ameliorates renal injury by reducing inflammation, oxidative stress, and lipid accumulation.
• The therapeutic effects of RSV are, at least partially, mediated through the activation of the PPAR-α signaling pathway and enhanced lipid catabolism.