A NONHUMAN PRIMATE MODEL FOR THE LINK BETWEEN CHILDHOOD ASTHMA & OBESITY

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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. The incidence of both childhood asthma and obesity has increased alarmingly in recent years. 17% of children are now obese and 35% are overweight. Multiple studies have clearly demonstrated that obesity increases the risk of developing childhood asthma but the underlying mechanisms are unknown and the optimum strategies to prevent the increased risk of asthma from obesity are also unknown. The purpose of this exploratory application is to utilize a non-human primate model to characterize the link between early onset obesity and asthma as a first step in developing potential therapeutic interventions. This model uses young adult monkeys chronically fed a typical American high fat (HF) diet. The high fat diet offspring show increased body fat, fatty liver and increased cytokine levels, all of which are consistent with human childhood obesity. The basic hypothesis of this application is that the HF diet offspring will show increased bronchial reactivity to challenge with ovalbumin as well as evidence of increased Th2 activation and inflammatory cytokine expression. Four basic criteria will be examined to characterize the model: innate airway hyperreactivity; allergic hyperreactivity; systemic and lung immune and cytokine responses; and changes in airway structure and geometry. In the first year of this proposal, offspring of HF and normal diet animals will be studied. A key aspect of this study will be to determine the ability of diet reversal interventions to reverse the airway reactivity changes induced by the HF diet and help break the link between obesity and asthma.