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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Short-term exposure to air pollution (PM2.5) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice

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Autor(es):
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Campolim, Clara Machado [1] ; Weissmann, Lais [2] ; de Oliveira Ferreira, Clilton Krauess [1] ; Zordao, Olivia Pizetta [2] ; Segantine Dornellas, Ana Paula [1] ; de Castro, Gisele [2] ; Zanotto, Tamires Marques [2] ; Boico, Vitor Ferreira [1] ; Fernandes Quaresma, Paula Gabriele [2] ; Ataide Lima, Raquel Patricia [1] ; Donato, Jose [3] ; Veras, Mariana Matera [4] ; Nascimento Saldiva, Paulo Hilario [4] ; Kim, Young-Bum [5] ; Prada, Patricia Oliveira [2, 1]
Número total de Autores: 15
Afiliação do(s) autor(es):
[1] State Univ Campinas UNICAMP, Sch Appl Sci, Limeira, SP - Brazil
[2] State Univ Campinas UNICAMP, Sch Med Sci, Dept Internal Med, Campinas, SP - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Hosp Clin HCFMUSP, Lab Poluicao Atmosfer Expt LIM05, Fac Med, Sao Paulo, SP - Brazil
[5] Harvard Med Sch, Div Endocrinol Diabet & Metab, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 JUN 23 2020.
Citações Web of Science: 0
Resumo

A previous study demonstrated that a high-fat diet (HFD), administered for one-three-days, induces hypothalamic inflammation before obesity's established, and the long term affects leptin signaling/action due to inflammation. We investigate whether exposure to particulate matter of a diameter of <= 2.5 mu m (PM2.5) in mice fed with a chow diet leads to similar metabolic effects caused by high-fat feeding. Compared to the filtered air group (FA), one-day-exposure-PM2.5 did not affect adiposity. However, five-days-exposure-PM2.5 increased hypothalamic microglia density, toll-like-receptor-4 (Tlr4), and the inhibitor-NF-kappa-B-kinase-epsilon (Ikbke) expression. Concurrently, fat mass, food intake (FI), and ucp1 expression in brown adipose tissue were also increased. Besides, decreased hypothalamic STAT3-phosphorylation and Pomc expression were found after twelve-weeks-exposure-PM2.5. These were accompanied by increased FI and lower energy expenditure (EE), leading to obesity, along with increased leptin and insulin levels and HOMA. Mechanistically, the deletion of Tlr4 or knockdown of the Ikbke gene in the hypothalamus was sufficient to reverse the metabolic outcomes of twelve-weeks-exposure-PM2.5. These data demonstrated that short-term exposure-PM2.5 increases hypothalamic inflammation, similar to a HFD. Long-term exposure-PM2.5 is even worse, leading to leptin resistance, hyperphagia, and decreased EE. These effects are most likely due to chronic hypothalamic inflammation, which is regulated by Tlr4 and Ikbke signaling. (AU)

Processo FAPESP: 17/19703-2 - Impacto da exposição perinatal a poluentes ambientais na gênese da obesidade e diabetes mellitus tipo 2: aspectos metabólicos e epigenéticos
Beneficiário:Raquel Patricia Ataíde Lima
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 17/11518-1 - Estudo sobre os efeitosda poluição atmosférica na gênese da obesidade: o papel da ativação do toll like receptor 4 hipotalâmico
Beneficiário:Clara Machado Campolim
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 17/02983-2 - Ação do hormônio do crescimento no sistema nervoso: relevância para as funções neurais e na doença
Beneficiário:Jose Donato Junior
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/18498-6 - Impacto da exposição perinatal a poluentes ambientais na gênese da obesidade e diabetes mellitus tipo 2: aspectos metabólicos e epigenéticos
Beneficiário:Patrícia de Oliveira Prada
Modalidade de apoio: Auxílio à Pesquisa - Regular