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

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

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‐inflammat...

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Bibliographic Details
Published in:Journal of neuroendocrinology 2019-02, Vol.31 (2), p.e12673-n/a
Main Authors: Ramírez, Delia, Saba, Julieta, Turati, Juan, Carniglia, Lila, Imsen, Mercedes, Mohn, Claudia, Scimonelli, Teresa, Durand, Daniela, Caruso, Carla, Lasaga, Mercedes
Format: Article
Language:eng
Subjects:
Antioxidants
Astrocytes
Body weight
Glutathione
High fat diet
Hypothalamus
Inflammation
MC4R
Melanocortin
Melanocortin MC4 receptors
mRNA
Neuropeptides
Neuroprotection
Neurotrophic factors
Nuclear transport
Oxidation
Oxidative stress
Palmitic acid
Reactive oxygen species
Superoxide dismutase
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Summary: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.
ISSN:0953-8194
1365-2826