Obesity is a critical public health concern, with the number of overfed individuals now surpassing the number of underfed individuals worldwide. Indeed, the prevalence of obesity, along with its serious complications, is increasing substantially among children and adolescents. The key to addressing the obesity epidemic is through prevention rather than treatment, given the difficulty in losing weight once it has accumulated. In addition, the timing of prevention is critical, as weight gain during the first year of life, and potentially within the first weeks of life, is strongly associated with adolescent and adult adiposity. Thus, one target for obesity prevention should be feeding in early infancy. Breastfed infants have been repeatedly shown to be leaner than their formula-fed counterparts and less likely to develop overweight later in life. Despite significant epidemiologic evidence for this relationship, the mechanism accounting for this protection against later obesity has not been identified. Human milk is a complex mixture of proteins and enzymes known to influence infant development. Of these factors, the adipose-tissue derived protein adiponectin is a strong candidate to affect adiposity at a young age. Adiponectin circulates abundantly in human plasma, and is associated with lower adiposity and improved metabolic functioning in children and adults. We have recently identified adiponectin in human milk and initially explored its association with infant weight gain in a limited breastfeeding cohort. This application will analyze a large (n=285) NICHD-funded breastfeeding cohort, with extensive existing prospectively-collected anthropometric and nutrition data and banked milk and serum samples, to test the following hypotheses: 1) Higher intake of human milk adiponectin is associated with lower adiposity during the first two years of life, 2) Breastfeeding history and higher concentrations of human milk adiponectin influence infant serum adiponectin, and 3) Higher infant serum adiponectin is independently associated with lower adiposity during the first two years of life. This application uses a unique cohort study with data and banked samples that provides optimal opportunity to examine this novel hypothesis. The proposed study has translational potential for preventing childhood obesity, as identifying adiponectin's role in early adiposity may lead to improved supplementation of the infant diet, especially in situations when breastfeeding is not possible. [unreadable] [unreadable] [unreadable]