Air pollution has been a very significant environmental cause of diseases globally. Fine particulate matter (PM2.5) is one of the most toxic substances in air pollution and is associated with type 2 diabetes mellitus risk. However, there is a gap in knowledge regarding the effects of air pollution exposure on insulin resistance and obesity development. We aimed to investigate whether 3 months of PM2.5 exposure induces obesity, hypothalamic leptin resistance and inflammation in adult mice. Also, we aimed to determine whether PM2.5 exposure during pregnancy and lactation changes food intake (FI), energy expenditure, body composition and weight, glucose, and insulin metabolism in the offspring. Three months of PM2.5 exposure decreased O2 consumption measured by CLAMS, and increased body weight and fat mass in adult mice without FI changes. These mice presented hypothalamic leptin resistance with decreased STAT3 phosphorylation and enhanced IKK epsilon (IKKe) expression measured by immunofluorescence and Real-Time PCR. Knocking down IKKe, partially reversed this phenotype. PM2.5 exposure during pregnancy and lactation increased body weight and fat mass of male offspring, observed by a MicroPet CT analysis, accompanied by decreased FI and increased respiratory exchange ratio. Male offspring presented higher serum insulin levels and glucose intolerance measured by GTT despite normal insulin tolerance measured by ITT. Female offspring had no phenotype alterations, except by the light reduced food intake.

In conclusion, PM2.5 exposure during adulthood induced obesity, partially due to a marked reduction in energy expenditure caused by hypothalamic leptin resistance. Elevated inflammation may explain that with a significant role of IKKe in the hypothalamus. Air pollution exposure during pregnancy and lactation had a remarkable effect inducing obesity in the male offspring due to an energy unbalance, which may lead to increased insulin levels and glucose intolerance.


O.P. Zord o: None. L.W. Claro: None. P. Saldiva: None. J. Donato: None. M. Veras: None. P.O. Prada: None.

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