@misc{10481/68066,
year = {2021},
url = {http://hdl.handle.net/10481/68066},
abstract = {Obesity and diabetes are linked to an increased prevalence of kidney disease. Endoplasmic
reticulum stress has recently gained growing importance in the pathogenesis of obesity and diabetesrelated kidney disease. Melatonin, is an important anti-obesogenic natural bioactive compound.
Previously, our research group showed that the renoprotective effect of melatonin administration
was associated with restoring mitochondrial fission/fusion balance and function in a rat model of
diabesity-induced kidney injury. This study was carried out to further investigate whether melatonin
could suppress renal endoplasmic reticulum (ER) stress response and the downstream unfolded
protein response activation under obese and diabetic conditions. Zücker diabetic fatty (ZDF) rats
and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight
(BW)/day) (M–ZDF and M–ZL) or vehicle (C–ZDF and C–ZL) for 17 weeks. Western blot analysis of
ER stress-related markers and renal morphology were assessed. Compared to C–ZL rats, higher ER
stress response associated with impaired renal morphology was observed in C–ZDF rats. Melatonin
supplementation alleviated renal ER stress response in ZDF rats, by decreasing glucose-regulated
protein 78 (GRP78), phosphoinositol-requiring enzyme1α (IRE1α), and ATF6 levels but had no effect
on phospho–protein kinase RNA–like endoplasmic reticulum kinase (PERK) level. In addition,
melatonin supplementation also restrained the ER stress-mediated apoptotic pathway, as indicated
by decreased pro-apoptotic proteins phospho–c–jun amino terminal kinase (JNK), Bax, and cleaved
caspase-3, as well as by upregulation of B cell lymphoma (Bcl)-2 protein. These improvements were
associated with renal structural recovery. Taken together, our findings revealed that melatonin play a
renoprotective role, at least in part, by suppressing ER stress and related pro-apoptotic IRE1α/JNK
signaling pathway.},
organization = {Spanish Government

SAF2016-79794-R},
organization = {European Commission},
publisher = {MDPI},
keywords = {Melatonin},
keywords = {Endoplasmic reticulum stress},
keywords = {Diabesity},
keywords = {Kidneys},
title = {Melatonin Improves Endoplasmic Reticulum Stress-Mediated IRE1α Pathway in Zucker Diabetic Fatty Rat},
doi = {10.3390/ph14030232},
author = {Aouichat, Samira and Navarro Alarcón, Miguel and Alarcón Guijo, Pablo and Salagre Simón, Diego and Agil Abdalla, Mhmad Ahmad},
}