MATERNAL OBESITY, INFLAMMATION AND EPIGENETIC MODIFICATIONS IN FETAL INTESTINE

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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 obesity rate increased more than 2 fold in recent decades. According to the latest NHANES survey (1999-2002), 29% of non-pregnant women 20-39 years of age are obese. At the same time, food allergy and related mucosal inflammatory diseases in gastrointestinal tract (GI) is also increasing (3.4% of all American have food allergy but more than 5% for children under 3 years old). Major steps of mucosal immune system development are accomplished during the fetal stage. We hypothesize that maternal obesity (MO) induces systemic inflammation in fetal GI tract, which enhances pro-inflammatory cytokine expression in gut mucosa, favoring inflammatory immune response which is associated with GI inflammatory diseases. We will use our well-established obese pregnant sheep model - ewes fed 100% (Con) or 150% of nutrient requirements (OB) to study the effect of MO on mucosal immune system (MIS) development. Due to the similarity of fetal development with the human fetus, pregnant sheep are one of the most powerful and widely used models for fetal development studies that relate to important problems in human pregnancy. MIS is responsible for the defense of tremendous amount of bacteria and opportunistic pathogens in GI tract and their proper development is crucial for lifelong health. Knowledge obtained in this study will provide targets for interventions to ensure proper development of MIS, improving the quality of life for the increasing number of obese people, as well as people suffered by allergic diseases in this country.