Postnatal weight gain induced by overfeeding pups and maternal high-fat diet during the lactation period modulates glucose metabolism and the production of pancreatic and gastrointestinal peptides

• We reported that two paradigms of early postnatal excessive weight gain had different effects on glucose homeostasis and the production of pancreatic and gastrointestinal peptides.
• Early postnatal overfeeding caused insulin resistance along with compensatory hyperinsulinemia and incretin production in pups.
• Maternal high-fat diet during lactation modified the fatty acid composition of breast milk, and led to insulin resistance accompanied by insufficient insulin secretion and incretin production in the offspring.
• Dietary nutrition might have a primary effect on acyl modification of ghrelin during the early postnatal period.

The impact of rapid weight gain on glucose metabolism during the early postnatal period remains unclear. We investigated the influence of rapid weight gain under different nutritional conditions on glucose metabolism, focusing on the production of pancreatic and gastric peptides. On postnatal day (PND) 2, C57BL/6N pups were divided into three groups: control (C) pups whose dams were fed a control diet (10%kcal fat) and nursed 10 pups each; maternal high-fat diet (HFD) pups whose dams were fed an HFD (45%kcal fat) and nursed 10 pups each; and overfeeding (OF) pups whose dams were fed the control diet and nursed 4 pups each. Data were collected on PND 7, 14 and 21. The body weight gains of the HFD and OF pups were 1.2 times higher than that of the C pups. On PND 14, the HFD pups had higher blood glucose levels, but there were no significant differences in serum insulin levels between the HFD and C pups. The OF pups had higher blood glucose and serum insulin levels than that of the C pups. Insulin resistance was found in the HFD and OF pups. On PND 14, the content of incretins in the jejunum was increased in the OF pups, and acyl ghrelin in the stomach was upregulated in the HFD and OF pups. These results suggest that neonatal weight gain induced by overfeeding pups and maternal high-fat diet during the early postnatal period modulates the insulin sensitivity and the production of pancreatic and gastrointestinal peptides.