L-carnitine is an amino acid essential for the oxidation of long-chain fatty acids to provide cellular energy. Carnitine is of particular importance during periods of dependence on fatty acids as an energy source, such as during starvation or during infancy. Although it known to be endogenously synthesized in both adult and developing mammals, evidence has increasingly suggested that milk-borne carnitine may play an essential role in fat utilization during normal development. Through pursuit of the following SPECIFIC AIMS, we propose to test the hypothesis that transport of carnitine present in breast milk is uniquely controlled during the suckling period to maintain adequate tissue levels for optimal fatty acid oxidation and that the gastrointestinal tract regulates carnitine transport into the body in response to both developmental and dietary changes.
Specific Aims Through the use of a suckling rat model fed a rat milk substitute completely lacking carnitine and a series of in vivo and in vitro techniques, we propose to test the hypothesis that: 1. the gastrointestinal tract of the suckling animal is especially suited for the accelerated transport and metabolism of carnitine compared to later periods of development. The characteristics of carnitine and carnitine ester transport by various portions of the gastrointestinal tract (stomach, duodenum, jejunum, ileum, and colon) during development will be determined. 2. gastrointestinal carnitine transport and metabolism is regulated by variables that include a) stage of development, b) the lipid content of the diet, and c) the carnitine content of the diet. Particular emphasis will be placed on examining the specific roles that each of these factors plays in the regulation of gastrointestinal carnitine transport and metabolism and the mechanism of such regulation as influenced by endocrine hormones of nutritional and developmental importance including glucagon, insulin, corticosterone, and thyroxine. 3. an active enterohepatic circulation of carnitine regulates the size and nature of the gastrointestinal carnitine pool as a function of nutritional state, diet composition, and development. Emphasis will be placed on defining the extent and kinetics of the enterohepatic circulation and identification of the specific factors that regulate the characteristics of carnitine transport and metabolism into bile. 4. dietary deprivation of carnitine interferes with normal gastric emptying and macronutrient absorption during development.
| Flores, C A; Hu, C; Edmond, J et al. (1996) Milk carnitine affects organ carnitine concentration in newborn rats. J Nutr 126:1673-82 |
