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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD030745-05
Application #
2403321
Study Section
Nutrition Study Section (NTN)
Project Start
1993-07-06
Project End
1999-06-30
Budget Start
1997-07-01
Budget End
1999-06-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kristan, D M; Hammond, K A (2000) Combined effects of cold exposure and sub-lethal intestinal parasites on host morphology and physiology. J Exp Biol 203:3495-504
Hammond, K A; Kristan, D M (2000) Responses to lactation and cold exposure by deer mice (Peromyscus maniculatus). Physiol Biochem Zool 73:547-56
O'Connor, T P; Lam, M M; Diamond, J (1999) Magnitude of functional adaptation after intestinal resection. Am J Physiol 276:R1265-75
O'Connor, T P; Diamond, J (1999) Ontogeny of intestinal safety factors: lactase capacities and lactose loads. Am J Physiol 276:R753-65
Hammond, K A; Janes, D N (1998) The effects of increased protein intake on kidney size and function. J Exp Biol 201:2081-90
Lee, E A; Weiss, S L; Lam, M et al. (1998) A method for assaying intestinal brush-border sucrase in an intact intestinal preparation. Proc Natl Acad Sci U S A 95:2111-6
Ferraris, R P; Diamond, J (1997) Regulation of intestinal sugar transport. Physiol Rev 77:257-302
Hammond, K A; Lam, M; Lloyd, K C et al. (1996) Simultaneous manipulation of intestinal capacities and nutrient loads in mice. Am J Physiol 271:G969-79
Hammond, K A; Lloyd, K C; Diamond, J (1996) Is mammary output capacity limiting to lactational performance in mice? J Exp Biol 199:337-49