NDP‐MSH reduces oxidative damage induced by palmitic acid in primary astrocytes

DELIA RAMÍREZ; JULIETA SABA; TURATI, JUAN; IMSEN, MERCEDES; CARNIGLIA, LILA; CLAUDIA MOHN; SCIMONELLI, TERESA N.; DANIELA DURAND; CARLA CARUSO; LASAGA, MERCEDES

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2019

0953-8194

Recent findings relate obesity to inflammation in key hypothalamic areas for body weight control. Hypothalamic inflammation has also been related to oxidative stress. Palmitic acid (PA ) is the most abundant free fatty acid found in food, and in vitro studies indicate that it triggers a pro‐inflammatory response in the brain. Melanocortins are neuropeptides with proven anti‐inflammatory and neuroprotective action mediated by melanocortin receptor 4 (MC 4R), but little is known about the effect of melanocortins on oxidative stress. The aim of this study was to investigate whether melanocortins could alleviate oxidative stress induced by a high fat diet (HFD ) model. We found that NDP ‐MSH treatment decreased PA ‐induced reactive oxygen species production in astrocytes, an effect blocked by the MC 4R inhibitor JKC 363. NDP ‐MSH abolished nuclear translocation of Nrf2 induced by PA and blocked the inhibitory effect of PA on superoxide dismutase (SOD ) activity and glutathione levels while it also per se increased activity of SOD and γ‐glutamate cysteine ligase (γ‐GCL ) antioxidant enzymes. However, HFD reduced hypothalamic MC 4R and brain derived neurotrophic factor mRNA levels, thereby preventing the neuroprotective mechanism induced by melanocortins.