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The overall goal of this research project is to determine the cellular and molecular mechanisms by which THS exposure results in insulin resistance. THS exposure can be defined as coming into contact with surfaces that have been exposed to second hand smoke (SHS). SHS toxins remain and accumulate on these surfaces and dust in places where smoking occurs or has occurred, and can be absorbed through the skin or inhaled, as they are re-emitted into the air. Our findings, after testing in humans, could inform the regulation of tobacco products to protect public health. In the US, nearly 88 million nonsmokers aged 3 or older live in homes where they are exposed to sufficient SHS to produce blood cotinine (a metabolite of nicotine) levels of ≥0.05 ng/ml. When smoking occurs indoors or in vehicles, the exposure to THS is unavoidable because extensive levels of SHS toxicants are deposited on environmental surfaces and undergo “aging” by reacting with the oxygen and nitrogen in the air, creating a new, hidden, threat to human health. The implications for public health of exposure to THS, via inhalation, ingestion and skin adsorption/absorption, are only now beginning to be realized. Particularly at risk are infants and children who play on the floor, lick their fingers, etc.
We hypothesize that THS exposure causes insulin resistance by increasing oxidative stress in the skeletal muscle and causing alterations to levels of insulin signaling hormones, resulting in cell death, inflammation and alterations to insulin signaling molecules. We will expose mice at weaning to THS using our novel system that mimics exposure of humans, and then collect blood, urine and tissue samples to determine the effects of these toxicants on the following: Aim #1 Determine whether THS-exposure results in increases cellular oxidative stress leading to cell damage and alteration of the gene expression and/or activation of molecules involved in insulin signaling; Aim #2 Determine whether THS stimulates alterations in metabolic hormones that result in insulin resistance.
Significance: Our studies address for the first time the fundamental nature of organ damage in a well-controlled animal system that mimics exposure of humans to THS. Obtaining this proposed scientific, well-controlled evidence will make a major step forward in the field and will provide regulatory agencies with information to guide studies in humans that will then allow regulation of THS exposure. Our results will also provide new evidence that will allow identification of new areas of research and help elucidate how insulin resistance can occur in absence of obesity, and how it is affected by genetics.
Impact: These findings will impact the field of THS by revealing the health risks associated with THS exposure and it will provide knowledge that will help establish guidelines for comparable studies in humans which can then result in policies that reduce/eliminate THS exposure. This work could also have an impact on finding out whether normal weight type II diabetes observed in 15% of diabetic humans is due to increases in every-day-life stress.
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