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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| Veröffentlicht in: | Journal of neuroendocrinology 2019-02, Vol.31 (2), p.e12673-n/a |
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| container_title | Journal of neuroendocrinology |
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| creator | Ramírez, Delia Saba, Julieta Turati, Juan Carniglia, Lila Imsen, Mercedes Mohn, Claudia Scimonelli, Teresa Durand, Daniela Caruso, Carla Lasaga, Mercedes |
| description | 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. |
| doi_str_mv | 10.1111/jne.12673 |
| format | Article |
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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.</description><identifier>ISSN: 0953-8194</identifier><identifier>EISSN: 1365-2826</identifier><identifier>DOI: 10.1111/jne.12673</identifier><identifier>PMID: 30712280</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>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</subject><ispartof>Journal of neuroendocrinology, 2019-02, Vol.31 (2), p.e12673-n/a</ispartof><rights>2019 British Society for Neuroendocrinology</rights><rights>2019 British Society for Neuroendocrinology.</rights><rights>Copyright © 2019 British Society for Neuroendocrinology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3883-9fbe40f3daabdba87c08bbc772a9ae164e1584bd084d20de5544368f785e26203</citedby><cites>FETCH-LOGICAL-c3883-9fbe40f3daabdba87c08bbc772a9ae164e1584bd084d20de5544368f785e26203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjne.12673$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjne.12673$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30712280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramírez, Delia</creatorcontrib><creatorcontrib>Saba, Julieta</creatorcontrib><creatorcontrib>Turati, Juan</creatorcontrib><creatorcontrib>Carniglia, Lila</creatorcontrib><creatorcontrib>Imsen, Mercedes</creatorcontrib><creatorcontrib>Mohn, Claudia</creatorcontrib><creatorcontrib>Scimonelli, Teresa</creatorcontrib><creatorcontrib>Durand, Daniela</creatorcontrib><creatorcontrib>Caruso, Carla</creatorcontrib><creatorcontrib>Lasaga, Mercedes</creatorcontrib><title>NDP‐MSH reduces oxidative damage induced by palmitic acid in primary astrocytes</title><title>Journal of neuroendocrinology</title><addtitle>J Neuroendocrinol</addtitle><description>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.</description><subject>Antioxidants</subject><subject>Astrocytes</subject><subject>Body weight</subject><subject>Glutathione</subject><subject>High fat diet</subject><subject>Hypothalamus</subject><subject>Inflammation</subject><subject>MC4R</subject><subject>Melanocortin</subject><subject>Melanocortin MC4 receptors</subject><subject>mRNA</subject><subject>Neuropeptides</subject><subject>Neuroprotection</subject><subject>Neurotrophic factors</subject><subject>Nuclear transport</subject><subject>Oxidation</subject><subject>Oxidative stress</subject><subject>Palmitic acid</subject><subject>Reactive oxygen species</subject><subject>Superoxide dismutase</subject><issn>0953-8194</issn><issn>1365-2826</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp10LtOwzAUBmALgWgpDLwAssQCQ1pfcnFGVAoFlZuAOXLsE-QqaUqcANl4BJ6RJ8ElhQEJLx7Op98-P0L7lAypO6P5AoaUhRHfQH3Kw8BjgoWbqE_igHuCxn4P7Vg7J4RGASfbqMdJRBkTpI_urk9vP98_ru6nuALdKLC4fDNa1uYFsJaFfAJsFquBxmmLlzIvTG0UlspoN8DLyhSyarG0dVWqtga7i7YymVvYW98D9Hg2eRhPvdnN-cX4ZOYpLgT34iwFn2RcS5nqVIpIEZGmKoqYjCXQ0AcaCD_VRPiaEQ1B4Ps8FFkkAmAhI3yAjrrcZVU-N2DrpDBWQZ7LBZSNTRiN3PpU-IGjh3_ovGyqhfudU8I9w7mInTrulKpKayvIkvVyCSXJqufE9Zx89-zswTqxSQvQv_KnWAdGHXg1ObT_JyWX15Mu8gtLDIbH</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Ramírez, Delia</creator><creator>Saba, Julieta</creator><creator>Turati, Juan</creator><creator>Carniglia, Lila</creator><creator>Imsen, Mercedes</creator><creator>Mohn, Claudia</creator><creator>Scimonelli, Teresa</creator><creator>Durand, Daniela</creator><creator>Caruso, Carla</creator><creator>Lasaga, Mercedes</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201902</creationdate><title>NDP‐MSH reduces oxidative damage induced by palmitic acid in primary astrocytes</title><author>Ramírez, Delia ; 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| 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 |
| title | NDP‐MSH reduces oxidative damage induced by palmitic acid in primary astrocytes |
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