Symposium: Animal Models in neonatal and Infant Nutrition Research Overview of Pup in a Cup Model: Hepatic Lipogenesis in Rats Artificially Reared on a High-Carbohydrate Formula12 MÃoeLCHAND S. PATEL,3 SATYA PRASAD VADLAMUDI AND GARY L. JOHA/W/YG4 Department of Biochemistry and Pew Center for Molecular Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106 ABSTRACT The artificial rearing technique allows nu tritional investigations to be conducted in rat pups dur ing a critical period that previously has been inacces sible to researchers. The technique will be useful for identifying dietary components contributing to meta bolic adaptations in the preweaning period as well as "metabolic imprinting" or permanent metabolic effects in adult rats resulting from early dietary intervention. Artificially reared rat pups fed a formula high in car bohydrate-derived energy in the preweaning period have the following characteristics compared with pups fed a high-fat formula or reared naturally: (i) a higher level of plasma insulin, (ii) an increased hepatic lipogenic capacity and (iii) precocious induction of hepatic malic enzyme. The results also show that early exposure to a high-carbohydrate diet in the preweaning period pre disposes the rat to an increased lipogenic capacity in liver and adipose tissues and to the development of obesity later in adult life. J. Nutr. 123:373-377,1993. INDEXING KEY WORDS: •artificial rearing technique •rat pups •milk substitute formulas •hepatic lipogenesis •plasma insulin The nutritional status of the neonate has important long-term metabolic and health consequences in adult life (1,2). The composition of nutrients fed to newborn suckling laboratory animals is difficult to control be cause of the necessary maternal involvement in the suckling process. Nutritional studies conducted dur ing this critical period of development in experimental animals are thus frequently compromised because of the inability to precisely regulate the composition of the diet during this period. In this report we will first present a brief description of the artificial rearing technique, which can be used to overcome some of the limitations described above. We will then present 0022-3166/93 S3.00 ©1993American Institute of Nutrition. results of studies using this technique to show how early nutritional modifications (such as a diet high in carbohydrate) can have (i)short-term effects (metabolic adaptations) and (ii) long-term consequences (meta bolic imprinting) related to lipid metabolism. Artificial rearing of rat pups The technique of gastric infusion was first described by Messer et al. (3), but the report of a nonsurgical technique by Hall (4) greatly improved the method by introducing two new procedures. The first is nonsur gical cannulation, in which a polyethylene cannula is used for infusing a formula directly into the stomach. The second innovation of Hall's procedure is the tech nique of artificially rearing the rats. Pups are reared in Styrofoam cups floating in a temperature-controlled water bath and are fed via flexible tubes connected to the cannula leading into the stomach. The formula is infused through syringes mounted to an automated infusion pump that can be kept in a refrigerator to prevent milk spoilage (5).The amount of milk supplied per day can be easily controlled. There are several advantages of the artificial rearing technique in nutrition research (4, 6). The most ob- 1 Presented as part of a symposium: Animal Models in Neonatal and Infant Nutrition Research, given at the 76th Annual Meeting of the Federation of American Societies for Experimental Biology, Anaheim, CA, April 8, 1992. This conference was sponsored by the American Institute of Nutrition. Guest editors for the symposium were Peggy R. Borum, Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL 32611, and Mul- chand S. Patel, Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106. 2The work reviewed in this article was supported by U. S. Public Health Service grants HD 11089 and HD 15778. 3To whom correspondence should be addressed: Department of Biochemistry, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4935. 4 Supported by the Metabolism Training grant AM 07319. 373 by guest on July 12, 2011 jn.nutrition.org Downloaded from