This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is associated with increased inflammation, insulin resistance and obstructive sleep apnea (OSA). From a long-term health standpoint, insulin resistance is the most significant of these issues;however, the etiologic link between obesity and insulin resistance has not been determined. Interestingly, increased systemic levels of S-nitrosylation (the addition of nitric oxide to cysteine moities in proteins) have also been linked to inflammation and insulin resistance, raising the possibility that a major source of insulin resistance in obesity could be via increased S-nitrosylation. One source of increased S-nitrosylation in obesity might be the high prevalence of undiagnosed OSA. We propose to test for levels of S-nitrosylated hemoglobin (SNO-Hb) among obese and lean adolescents before and after they undergo sleep studies. We can then examine whether levels of S-nitrosylation are indeed higher among obese adolescents vs. lean subjects. We can further test whether higher levels of SNO-Hb correlate with increased inflammation and insulin resistance. Knowledge of the role of S-nitrosylation in the production of insulin resistance could help in identifying children at increased risk for developing insulin resistance who would thus require earlier intervention. More importantly, discovery into the mechanistic link between obesity and insulin resistance would be useful for designing medical interventions to decrease insulin resistance and thus long-term risks of developing diabetes.
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