Development of Regulation of Food Intake by the Gut and the Brain: Modeling in Animals

Abstract

Before weaning by 16th or 17th day of postnatal life (P16 or P17), pups are attracted by olfactory cues to attach to the mother’s nipples. During suckling, pups exhibit a characteristic stretch reaction at each milk-ejection reflex that occurs intermittently. Suckling is a behavioral reflex devoid of control by internal stimuli that inhibit feeding in adult rats until about P15. Beyond this age, deprivation shortens and increases the latency of pups attachment latency to, and shifting of the anesthetized mother’s nipples, respectively, suggesting the emergence of hunger. From a developmental standpoint, suckling behavior is not a continuous adult-type feeding behavior. For instance, infusion of milk through a cannula placed in the posterior aspect of rat pups mouth induces the stretch reaction, resulting in a continuous withdrawal of milk until the pups’ stomach are fully distended and cannot retain any more milk. However, when the cannula is located on the anterior oral cavity, the pups stop ingesting infused milk when the gastric volume is about 5% of body weight. This latter behavior is known as controlled “independent ingestion” and believed to be a prototype of adult-type feeding behavior. In the first week of postnatal life, no differentiation can be made between pup eating and drinking behaviors. During this period, dehydration which inhibits food intake in adult rats is a critical physiological stimulus that increases milk intake. By P6, milk ingestion is regulated by a combination of sweet taste-dependent orosensory positive feedback mechanism and gastric volume-dependent negative feedback regulatory pathways. Differentiation of distinct regulatory controls for food and water become evident during the second week of postnatal life. During this period, corn oil becomes a potent stimulus for positive feedback regulation, while hypertonicity provides a stimulus for post-ingestive negative feedback mechanisms. Proteins in the diet inhibit pup food intake by P18 while glucose has no significant negative feedback effect during the first 3 weeks. Furthermore, glucoprivation induced by 2-deoxyglucose fails to stimulate food intake until the fourth postnatal week. In addition, leptin does not inhibit ingestion during the first 2–3 weeks of postnatal life, but alters neuronal activity in the arcuate nucleus as early as P6. This latter observation probably derives from the immaturity of the neuronal projecting from the arcuate nucleus to the target nuclei, which are critical for the regulation of energy balance. Consequently, the leptin surge during the second postnatal week may be responsible for the development of this feeding regulatory pathway.