Although leptin is a hormone mainly produced by the adipose tissue, it is also produced by the gastric mucosa and the mammary epithelium and is present in maternal milk. The effects of milk leptin on the neonate are not known. The purpose of the investigation was to evaluate the short-term effects of the administration of a single oral dose of leptin on 4-d-old rats as well as the effects of chronic supplementation during the lactation period with a daily oral dose of leptin (equivalent to 5 times the amount of leptin ingested normally from maternal milk during the suckling period) on body weight, the gastric leptin system, gastric food content, and thermogenic capacity. Our results show that the administration of a single oral dose of 4 ng of leptin to 4-d-old rats produces a short-term increase in leptin levels in the stomach and serum and a decrease in the weight of the gastric contents. Pups treated with a daily oral dose of leptin during the whole lactation period showed, at the end of the suckling period, compared with controls, lower gastric contents, lower leptin production by the stomach and the sc adipose tissue, and lower thermogenic capacity in brown adipose tissue. We conclude that oral leptin is absorbed by the immature gastric epithelium of the neonate, and this leptin exerts clear biological effects, down-regulating endogenous leptin production and playing a potential role in the short-term control on food intake during the lactation period.

We have previously described that neonate rats supplemented with physiological doses of oral leptin during lactation become more protected against overweight in adulthood. The purpose of this study was to characterize further the long-term effects on glucose and leptin homeostasis and on food preferences. Neonate rats were supplemented during lactation with a daily oral dose of leptin or the vehicle. We followed body weight and food intake of animals until the age of 15 months, and measured glucose, insulin, and leptin levels under different feeding conditions: ad libitum feeding, 14-h fasting, and 3-h refeeding after fasting. An oral glucose tolerance test and a leptin resistance test were performed. Food preferences were also measured. Leptin-treated animals were found to have lower body weight in adulthood and to eat fewer calories than their controls. Plasma insulin levels were lower in leptin-treated animals than in their controls under the different feeding conditions, as was the increase in insulin levels after food intake. The homeostatic model assessment for insulin resistance index was significantly lower in leptin-treated animals, and the oral glucose tolerance test also indicated higher insulin sensitivity in leptin-treated animals. In addition, these animals displayed lower plasma leptin levels under the different feeding conditions and were also more responsive to exogenous leptin administration. Leptin-treated animals also showed a lower preference for fat-rich food than their controls. These observations indicate that animals supplemented with physiological doses of oral leptin during lactation were more protected against obesity and metabolic features of the metabolic syndrome.