# Melatonin Administration Attenuates High-Fat-Diet-Induced Renal Damage in Wistar Rats

## TL;DR

Melatonin reduces kidney damage in obese rats by fighting inflammation and fibrosis, and may help treat obesity-related kidney disease.

## Contribution

Melatonin mitigates obesity-induced kidney injury through anti-fibrotic and anti-inflammatory effects, and reveals a novel link to circadian disruption.

## Key findings

- Melatonin reduced renal fibrosis, KIM-1, TGFβ, and TNFR1 levels in obese rats.
- Melatonin improved proximal tubule and glomerular damage and lowered adipose TNF-α levels.
- BMAL1 accumulation in distal tubular cytoplasm was observed in melatonin-treated groups.

## Abstract

Obesity is a major contributor to kidney injury, in part through circadian rhythms disruption and oxidative stress. Melatonin, a circadian clock regulator, has been proposed as a protective agent against metabolic and renal complications. We investigated the effects of chronic melatonin supplementation on kidney injury and circadian regulation in a rat obesity model. We hypothesized that melatonin administration ameliorates kidney injury induced by a high-calorie diet. Male Wistar rats were fed a normal or hypercaloric diet for six weeks, followed by seven weeks of vehicle or melatonin treatment (30 mg/kg/day in drinking water); biometric parameters and renal injury were assessed. Obese rats exhibited increased visceral adiposity, elevated resistin, renal hypertrophy, fibrosis, tubular degeneration, and glomerular injury, accompanied by higher KIM-1 levels. Melatonin attenuated renal fibrosis, reduced KIM-1, TGFβ, and TNFR1 levels, improved proximal tubule and glomerular damage, and lowered adipose TNF-α levels in the obese groups. In lean controls, melatonin increased nuclear BMAL1 levels, while in obese rats this effect was blunted; of note, BMAL1 accumulated in distal tubular cytoplasm in both melatonin-treated groups. These findings suggest that melatonin mitigates obesity-induced renal pathology through anti-fibrotic inflammation-related mechanisms, while also revealing a novel link between circadian disruption and kidney injury. Our results support melatonin as a therapeutic agent for obesity-related renal disease.