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

Abstract

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 (MC4R), 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 MC4R inhibitor JKC363. 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 MC4R and brain derived neurotrophic factor mRNA levels, thereby preventing the neuroprotective mechanism induced by melanocortins. K E Y W O R D Sastrocytes, high-fat diet, MC4R, oxidative stress, palmitic acid

NDP-MSH binding melanocortin-1 receptor ameliorates neuroinflammation and BBB disruption through CREB/Nr4a1/NF-κB pathway after intracerebral hemorrhage in mice

“…There are some limitations in our study. NDP-MSH had been reported to possess multiple beneficial properties in a central nervous system disease, including anti-inflammation, anti-apoptosis, and anti-oxidation [13, 31, 34, 38, 39]. In this study, we only investigated the neuroprotective functions of NDP-MSH on neuroinflammation and BBB integrity after ICH.…”

Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential

“…Some studies have associated SAFAs as a primary cause of cell death [ 108 ]. In this regard, it has been reported that PA could affect the cell viability of different brain cells, such as the neuroblastoma SH-SY5Y [ 109 ], glioblastoma T98G [ 110 , 111 ], microglial cells BV-2 [ 112 ], primary microglia [ 40 ], primary neurons [ 31 ], and primary astrocytes [ 113 , 114 , 115 , 116 ]. Although it is known that the PA could affect different brain cells through different cellular mechanisms, these are not clear.…”

Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor

“…Astrocytes were obtained from cerebral cortices of male/female 1-2-day-old Wistar rat pups, as previously described [15]. Wild-type and SR-A knockout mice-derived cortical astrocyte cultures were prepared using the protocol of von Bernhardi and Eugenín [16].…”