Pre- and postnatal nutrition in sheep affects β-cell secretion and hypothalamic control

Area of Science:

• Reproductive biology
• Metabolic programming
• Endocrinology

Background:

• Maternal undernutrition increases offspring risk for type 2 diabetes and metabolic syndrome, especially with postnatal high-energy diets.
• Early-life metabolic dysfunctions are often undetectable by conventional tests, hindering risk identification.
• Prenatal undernutrition may prime offspring for altered responses to nutritional challenges.

Purpose of the Study:

• To investigate the long-term metabolic and endocrine effects of prenatal undernutrition and postnatal high-carbohydrate-high-fat (HCHF) diet exposure in sheep.
• To determine if prenatal undernutrition leads to adaptive responses mimicking starvation or stress.
• To identify early markers of metabolic risk programmed by maternal nutrition.

Main Methods:

• Twin-pregnant sheep received either 100% (NORM) or 50% (LOW) energy/protein requirements during the last trimester.
• Offspring were fed a control (CONV) or HCHF diet from 3 days to 6 months, then CONV until 2 years.
• Offspring underwent fasting, propionate (nutrient abundance), and adrenalin challenges at 6 months and 2 years.

Main Results:

• Postnatal HCHF diet at 6 months induced hypertriglyceridemia and altered pancreatic beta-cell secretion.
• Prenatal undernutrition, regardless of postnatal diet, resulted in abnormal leptin, IGF1, and cortisol responses during fasting in 2-year-old adults.
• Maternal undernutrition alone did not alter offspring metabolism but induced aberrant hormonal responses, suggesting hypothalamic integration issues.

Conclusions:

• High-carbohydrate-high-fat diets negatively impact pancreatic beta-cell function.
• Prenatal undernutrition programs offspring for altered endocrine axis regulation, particularly affecting hypothalamic integration of hormonal responses to fasting.
• Fetal programming by maternal undernutrition can lead to subtle, yet significant, endocrine dysregulations detectable later in life.