Long-term exposure to air pollution may have unfavorable effects on health. Particulate matter (PM) diameter less than or equal to 2.5 µm (PM2.5) is associated with the induction of chronic inflammation. Obesity may be a consequence of the imbalance between food consumption and energy expenditure. JAK2 / STAT3 pathway in hypothalamic nuclei is an important hallmark of leptin signaling and has a role in maintaining energy homeostasis. In obesity state there is resistance to leptin. One of the mechanisms that triggers leptin resistance in obese individuals is the activation of low grade inflammation through innate receptors, such as toll-like receptor 4 (TLR4). Lipopolysaccharide (LPS) is a potent TLR4 agonist that triggers a signaling cascade downstream, leading to the activation of the NF-kB (nuclear factor kappa B) pathway, and consequently the transcription of pro-inflammatory genes. Many pro-inflammatory genes may be involved in the leptin signaling impairment, such as SOCS-3 (cytokine signal suppressor 3) and PTP1B (protein tyrosine phosphatase 1B). One of the components of PM2.5 is LPS, in that sense, we conceived the possibility that exposure to chronic pollution (PM2.5) might activate TLR4, inducing hypothalamic low grade inflammation, and leptin resistance. Therefore, the mains of the present study are to investigate: 1) TRL4 gene expression in the hypothalamus of C57BL / 6J mice submitted to MP2.5 compared to C57BL / 6J mice submitted to filtered air; 2) the changes in energy homeostasis (weight gain, changes in energy intake and energy expenditure, UCP-1 gene expression in brown adipose tissue, circulating hormone leptin, insulin, glucose, pro-inflammatory cytokines), glucose and insulin homeostasis in mice knockouts for TRL-4 (TLR4KO) when exposed to PM2.5 or filtered air; 3) the leptin sensitivity and leptin signaling in the hypothalamus of TLR4KO exposed to PM2.5 or filtered air, as well as the gene expression of neuropeptides (NPY, AgRP, POMC, CRH, TRH and orexin) in the hypothalamus of these same animals.
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