Short-term exposure to air pollution (PM 2.5 ) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice.

Autor: Campolim CM; School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil., Weissmann L; Department of Internal Medicine, School of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Ferreira CKO; School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil., Zordão OP; Department of Internal Medicine, School of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Dornellas APS; School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil., de Castro G; Department of Internal Medicine, School of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Zanotto TM; Department of Internal Medicine, School of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Boico VF; School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil., Quaresma PGF; Department of Internal Medicine, School of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Lima RPA; School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil., Donato J Jr; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil., Veras MM; Laboratório de Poluição Atmosférica Experimental LIM05, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil., Saldiva PHN; Laboratório de Poluição Atmosférica Experimental LIM05, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil., Kim YB; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Prada PO; School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil. pprada@unicamp.br.; Department of Internal Medicine, School of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil. pprada@unicamp.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Jun 23; Vol. 10 (1), pp. 10160. Date of Electronic Publication: 2020 Jun 23.
DOI: 10.1038/s41598-020-67040-3
Abstrakt: 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 μm (PM 2.5 ) 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-PM 2.5 did not affect adiposity. However, five-days-exposure-PM 2.5 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-PM 2.5 . 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-PM 2.5 . These data demonstrated that short-term exposure-PM 2.5 increases hypothalamic inflammation, similar to a HFD. Long-term exposure-PM 2.5 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.
Databáze: MEDLINE
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