Docosahexaenoic Acid Alleviates Palmitic Acid-Induced Inflammation of Macrophages via TLR22-MAPK-PPARγ/Nrf2 Pathway in Large Yellow Croaker (<i>Larimichthys crocea</i>)

Palmitic acid (PA) is a saturated fatty acid (SFA) that can cause an inflammatory response, while docosahexaenoic acid (DHA) is always used as a nutritional modulator due to its anti-inflammatory properties. However, the potential molecular mechanism is still not completely elucidated in fish. Herei...

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Main Authors: Dan Xu, Kun Cui, Qingfei Li, Si Zhu, Junzhi Zhang, Shengnan Gao, Tingting Hao, Kangsen Mai, Qinghui Ai
Format: Article
Sprog:English
Udgivet: MDPI AG 2022-03-01
Serier:Antioxidants
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Online adgang:https://www.mdpi.com/2076-3921/11/4/682
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author Dan Xu
Kun Cui
Qingfei Li
Si Zhu
Junzhi Zhang
Shengnan Gao
Tingting Hao
Kangsen Mai
Qinghui Ai
author_facet Dan Xu
Kun Cui
Qingfei Li
Si Zhu
Junzhi Zhang
Shengnan Gao
Tingting Hao
Kangsen Mai
Qinghui Ai
author_sort Dan Xu
collection DOAJ
description Palmitic acid (PA) is a saturated fatty acid (SFA) that can cause an inflammatory response, while docosahexaenoic acid (DHA) is always used as a nutritional modulator due to its anti-inflammatory properties. However, the potential molecular mechanism is still not completely elucidated in fish. Herein, the PA treatment induced an inflammatory response in macrophages of large yellow croaker (<i>Larimichthys crocea</i>). Meanwhile, the mRNA expression of Toll-like receptor (TLR)-related genes, especially <i>tlr22</i>, and the phosphorylation of the mitogen-activated protein kinase (MAPK) pathway were significantly upregulated by PA. Further investigation found that the PA-induced inflammatory response was suppressed by <i>tlr22</i> knockdown and MAPK inhibitors. Moreover, the results of the peroxisome proliferator-activated receptor γ (PPARγ) agonist and inhibitor treatment proved that PPARγ was involved in the PA-induced inflammation. PA treatment decreased the protein expression of PPARγ, while <i>tlr22</i> knockdown and MAPK inhibitors recovered the decreased expression. Besides, the PA-induced activation of Nrf2 was regulated by p38 MAPK. Furthermore, DHA-executed anti-inflammatory effects by regulating the phosphorylation of the MAPK pathway and expressions of PPARγ and Nrf2. Overall, the present study revealed that DHA alleviated PA-induced inflammation in macrophages via the TLR22-MAPK-PPARγ/Nrf2 pathway. These results could advance the understanding of the molecular mechanism of the SFA-induced inflammatory response and provide nutritional mitigative strategies.
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spelling doaj.art-aec26f49d8074f0fb19ab054dd20591f2023-12-01T00:34:59ZengMDPI AGAntioxidants2076-39212022-03-0111468210.3390/antiox11040682Docosahexaenoic Acid Alleviates Palmitic Acid-Induced Inflammation of Macrophages via TLR22-MAPK-PPARγ/Nrf2 Pathway in Large Yellow Croaker (<i>Larimichthys crocea</i>)Dan Xu0Kun Cui1Qingfei Li2Si Zhu3Junzhi Zhang4Shengnan Gao5Tingting Hao6Kangsen Mai7Qinghui Ai8Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaPalmitic acid (PA) is a saturated fatty acid (SFA) that can cause an inflammatory response, while docosahexaenoic acid (DHA) is always used as a nutritional modulator due to its anti-inflammatory properties. However, the potential molecular mechanism is still not completely elucidated in fish. Herein, the PA treatment induced an inflammatory response in macrophages of large yellow croaker (<i>Larimichthys crocea</i>). Meanwhile, the mRNA expression of Toll-like receptor (TLR)-related genes, especially <i>tlr22</i>, and the phosphorylation of the mitogen-activated protein kinase (MAPK) pathway were significantly upregulated by PA. Further investigation found that the PA-induced inflammatory response was suppressed by <i>tlr22</i> knockdown and MAPK inhibitors. Moreover, the results of the peroxisome proliferator-activated receptor γ (PPARγ) agonist and inhibitor treatment proved that PPARγ was involved in the PA-induced inflammation. PA treatment decreased the protein expression of PPARγ, while <i>tlr22</i> knockdown and MAPK inhibitors recovered the decreased expression. Besides, the PA-induced activation of Nrf2 was regulated by p38 MAPK. Furthermore, DHA-executed anti-inflammatory effects by regulating the phosphorylation of the MAPK pathway and expressions of PPARγ and Nrf2. Overall, the present study revealed that DHA alleviated PA-induced inflammation in macrophages via the TLR22-MAPK-PPARγ/Nrf2 pathway. These results could advance the understanding of the molecular mechanism of the SFA-induced inflammatory response and provide nutritional mitigative strategies.https://www.mdpi.com/2076-3921/11/4/682palmitic acidinflammatory responseToll-like receptordocosahexaenoic acid<i>Larimichthys crocea</i>
spellingShingle Dan Xu
Kun Cui
Qingfei Li
Si Zhu
Junzhi Zhang
Shengnan Gao
Tingting Hao
Kangsen Mai
Qinghui Ai
Docosahexaenoic Acid Alleviates Palmitic Acid-Induced Inflammation of Macrophages via TLR22-MAPK-PPARγ/Nrf2 Pathway in Large Yellow Croaker (<i>Larimichthys crocea</i>)
Antioxidants
palmitic acid
inflammatory response
Toll-like receptor
docosahexaenoic acid
<i>Larimichthys crocea</i>
title Docosahexaenoic Acid Alleviates Palmitic Acid-Induced Inflammation of Macrophages via TLR22-MAPK-PPARγ/Nrf2 Pathway in Large Yellow Croaker (<i>Larimichthys crocea</i>)
title_full Docosahexaenoic Acid Alleviates Palmitic Acid-Induced Inflammation of Macrophages via TLR22-MAPK-PPARγ/Nrf2 Pathway in Large Yellow Croaker (<i>Larimichthys crocea</i>)
title_fullStr Docosahexaenoic Acid Alleviates Palmitic Acid-Induced Inflammation of Macrophages via TLR22-MAPK-PPARγ/Nrf2 Pathway in Large Yellow Croaker (<i>Larimichthys crocea</i>)
title_full_unstemmed Docosahexaenoic Acid Alleviates Palmitic Acid-Induced Inflammation of Macrophages via TLR22-MAPK-PPARγ/Nrf2 Pathway in Large Yellow Croaker (<i>Larimichthys crocea</i>)
title_short Docosahexaenoic Acid Alleviates Palmitic Acid-Induced Inflammation of Macrophages via TLR22-MAPK-PPARγ/Nrf2 Pathway in Large Yellow Croaker (<i>Larimichthys crocea</i>)
title_sort docosahexaenoic acid alleviates palmitic acid induced inflammation of macrophages via tlr22 mapk pparγ nrf2 pathway in large yellow croaker i larimichthys crocea i
topic palmitic acid
inflammatory response
Toll-like receptor
docosahexaenoic acid
<i>Larimichthys crocea</i>
url https://www.mdpi.com/2076-3921/11/4/682
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