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Cited by 76Adipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and ObesityAir Quality and Health Impacts

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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Campolim, Clara Machado, Weissmann, Lais, Ferreira, Clílton Kraüss de Oliveira, Zordão, Olivia Pizetta, Dornellas, Ana Paula Segantine, de Castro, Gisele, Zanotto, Tamires Marques, Boico, Vitor Ferreira +7 more·2020·Scientific Reports
DOI 10.1038/s41598-020-67040-3PMC PMC7311527
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Abstract

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.

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  • Genetic or pharmacologic treatments that increase microgliosis within the mediobasal hypothalamus are capable of inducing obesity even in the absence of dietary challenge.

    “It has also been reported that genetic or pharmacologic treatments that increase microgliosis within the mediobasal hypothalamus are capable of inducing obesity even in the absence of dietary challenge (Valdearcos et al., 2017; Campolim et al., 2020).”

    From Deletion of the Alzheimer’s disease risk gene Abi3 locus results in obesity and systemic metabolic disruption in mice (2022) · cites this paper as Campolim et al., 2020

    The Discussion (page unavailable) reports increased hypothalamic Iba1, a marker of microglial activation, after five days of PM2.5 exposure; the Results report obesity after 12 weeks, and the Methods specify standard chow. This supports microglial activation and subsequent obesity without a high-fat diet, but the intervention was air-pollution exposure—not a genetic or pharmacologic treatment that increased microgliosis—and the paper does not establish that microgliosis itself induced obesity. (LLM, conf=0.86)

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Authors
Campolim, C. M., Weissmann, L., Ferreira, C. K. D. O., Zordão, O. P., Dornellas, A. P. S., de Castro, G., Zanotto, T. M., Boico, V. F., Quaresma, P. G. F., Lima, R. P. A., Donato, J., Veras, M. M., Saldiva, P. H. N., Kim, Y.-B., & Prada, P. O.
Affiliations
  • Universidade Estadual de Campinas (UNICAMP) (BR)
  • Universidade de São Paulo (BR)
  • Beth Israel Deaconess Medical Center (US)
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-06-23
Volume
10
Issue
1
Pages
10160-10160
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-67040-3
PMC
PMC7311527
OpenAlex
W3035800398
Cited by
76
References
3
Citations by year
2026: 7 · 2025: 15 · 2024: 15 · 2023: 15 · 2022: 15 · 2021: 9
FWCI
6.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (2017/11518-1, 17/02983-2, 17/18498-6)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (573856/2008–7)
  • Instituto Nacional de Ciência e Tecnologia de Obesidade e Diabetes (573856/2008-7)
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106076)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
Keywords
PM2.5, particulate matter exposure, hypothalamic inflammation, leptin resistance, obesity, TLR4, IKBKE, microglia, hyperphagia, energy expenditure, brown adipose tissue, STAT3 phosphorylation, proopiomelanocortin, insulin resistance
MeSH terms
Uncoupling Protein 1, Air Pollution, Animals, Energy Metabolism, Hyperphagia, Hypothalamus, Inflammation, Mice, Transgenic, Obesity, Time Factors, Signal Transduction, Gene Expression, Microglia, Leptin, Toll-Like Receptor 4, I-kappa B Kinase, Adipocytes, Brown, Particulate Matter

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