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

Abstract

Young-Bum Kim 5 & patricia oliveira prada 1,2 ✉ 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-weeksexposure-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.

Effect of ozone exposure on Amyotrophic Lateral Sclerosis (ALS) pathology using a mice model of TDP-43 proteinopathy

“…In contrast to these results, we find that O3 exposure had a significant effect on the plasma concentration of leptin in WT controls. Likewise, a positive correlation was found among the plasmatic levels of GIP and glucagon relative to insulin concentrations in this group, supporting previous experiments conducted in rodents, which strongly associated exposure to O3 with the development of obesity and diabetes type II (Campolim et al 2020).…”

Nontraditional Risk Factors for Obesity in Modern Society

“…Thus, it increases the expression of proinflammatory genes. 42 , 43 Campolim et al 44 investigated whether a reaction similar to the metabolic effect of a high-fat diet appeared when exposed to PM 2.5 in mice fed a chow diet. Compared to the filtered air group, the group exposed to PM 2.5 for 5 days had increased microglial density and expression of TLR4 and inhibitor-NF-κB-kinase-epsilon (Ikbkε); meanwhile, the amount of fat and food intake increased.…”

The Impact of PM2.5 on the Growth Curves of Children's Obesity Indexes: A Prospective Cohort Study

“…Currently, several studies illustrated the mechanism of how PM2.5 induced obesity. A previous study found that long-term PM2.5 exposure in mice leads to obesity via TLR4/Ikbke ( 45 ), which increased the risk of obesity and metabolic syndrome, and inflammatory activation regulated by TLR2/4 and lung lipid oxidation lead to abnormal metabolic function and obesity ( 46 ). The specific molecular biological mechanism remains to be confirmed in future studies.…”