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

Autor(es):Mostrar menos -

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]}

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

• 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