The long-term goal is to understand how a lactating mother's gut meets the mother's increased requirement for nutrients to be exported into milk. The driving motivations are the physiological and clinical significance of lactation, and the advantages of the gut/mammary gland interface as a model for attacking broad questions of quantitative integration within the body.
The specific aims, utilizing mouse models, include the following: 1. To identify the ceiling value of dietary nutrient intake during lactation: is it limited to the caloric equivalent of about seven times the basal metabolic rate? 2. To identify the proximate factors limiting lactational nutrient output. Candidate factors include the dietary supply of certain nutrients, mammary milk- producing capacity, intestinal digestive capacity, or the latter two factors matched to each other. 3. To test how physiological capacities are matched to each other and to demand during lactation. Capacities may impose bottlenecks on performance or may exceed demand by some reserve capacity, while series capacities may not to matched to each other. The research design includes experimentally pushing the energy burden of lactation towards a limit by expanding litter size, extending the duration of lactation, or combining the burden of lactation with the burden of increased heat production as low ambient temperatures; varying intestinal digestive capacity surgically, by partial resection of the small intestine; and varying mammary gland secretory capacity surgically, by selective ablation. Activities and capacities of intestinal brush- border and basolateral nutrient transporters and brush-border hydrolases will be measured for comparison with dietary intakes of their substrates.
