[PMID]: | 28771483 |
[Au] Autor: | Pepping JK; Vandanmagsar B; Fernandez-Kim SO; Zhang J; Mynatt RL; Bruce-Keller AJ |
[Ad] Endereço: | Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, United States of America. |
[Ti] Título: | Myeloid-specific deletion of NOX2 prevents the metabolic and neurologic consequences of high fat diet. |
[So] Source: | PLoS One;12(8):e0181500, 2017. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | High fat diet-induced obesity is associated with inflammatory and oxidative signaling in macrophages that likely participates in metabolic and physiologic impairment. One key factor that could drive pathologic changes in macrophages is the pro-inflammatory, pro-oxidant enzyme NADPH oxidase. However, NADPH oxidase is a pleiotropic enzyme with both pathologic and physiologic functions, ruling out indiscriminant NADPH oxidase inhibition as a viable therapy. To determine if targeted inhibition of monocyte/macrophage NADPH oxidase could mitigate obesity pathology, we generated mice that lack the NADPH oxidase catalytic subunit NOX2 in myeloid lineage cells. C57Bl/6 control (NOX2-FL) and myeloid-deficient NOX2 (mNOX2-KO) mice were given high fat diet for 16 weeks, and subject to comprehensive metabolic, behavioral, and biochemical analyses. Data show that mNOX2-KO mice had lower body weight, delayed adiposity, attenuated visceral inflammation, and decreased macrophage infiltration and cell injury in visceral adipose relative to control NOX2-FL mice. Moreover, the effects of high fat diet on glucose regulation and circulating lipids were attenuated in mNOX2-KO mice. Finally, memory was impaired and markers of brain injury increased in NOX2-FL, but not mNOX2-KO mice. Collectively, these data indicate that NOX2 signaling in macrophages participates in the pathogenesis of obesity, and reinforce a key role for macrophage inflammation in diet-induced metabolic and neurologic decline. Development of macrophage/immune-specific NOX-based therapies could thus potentially be used to preserve metabolic and neurologic function in the context of obesity. |
[Mh] Termos MeSH primário: |
Cognição Dieta Hiperlipídica/efeitos adversos Deleção de Genes Glicoproteínas de Membrana/deficiência Glicoproteínas de Membrana/genética Células Mieloides/metabolismo NADPH Oxidases/deficiência NADPH Oxidases/genética
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[Mh] Termos MeSH secundário: |
Animais Composição Corporal/genética Peso Corporal/genética Encéfalo/fisiologia Linhagem da Célula Técnicas de Inativação de Genes Gordura Intra-Abdominal/metabolismo Camundongos NADPH Oxidase 2
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Membrane Glycoproteins); EC 1.6.3.- (Cybb protein, mouse); EC 1.6.3.- (NADPH Oxidase 2); EC 1.6.3.- (NADPH Oxidases) |
[Em] Mês de entrada: | 1708 |
[Cu] Atualização por classe: | 171116 |
[Lr] Data última revisão:
| 171116 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170804 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0181500 |
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