Compromised beta-cell development and beta-cell dysfunction in weanling offspring from dams maintained on a high-fat...

Area of Science:

• Endocrinology
• Developmental Biology
• Nutritional Science

Background:

• Maternal diet during pregnancy significantly influences offspring metabolic health.
• High-fat diets (HFD) are increasingly prevalent and may pose risks to fetal development.
• Understanding the critical windows of exposure during gestation is crucial for preventing metabolic disorders.

Purpose of the Study:

• To investigate the impact of maternal HFD exposure during specific weeks of gestation on weanling offspring.
• To assess effects on body weight, pancreatic beta- and alpha-cell development, and beta-cell function.
• To determine if the timing of HFD exposure during pregnancy alters offspring outcomes.

Main Methods:

• Offspring were derived from dams fed an HFD during the first, second, third, or entire gestation period.
• Weanling body weight, glucose, and insulin levels were measured at postnatal day 21.
• Pancreatic tissues were analyzed for beta- and alpha-cell parameters and glucokinase (GK) expression via qPCR and immunohistochemistry.

Main Results:

• All weanlings exhibited low body weight and hypoinsulinemia.
• Maternal HFD during any single week of gestation resulted in hyperglycemia and reduced beta-cell volume, number, and size.
• Impaired GK mRNA expression and immunoreactivity were observed in offspring exposed to HFD during specific gestational weeks.
• Beta- and alpha-cell development were normal in offspring from dams fed HFD throughout gestation.

Conclusions:

• Maternal HFD exposure during any single week of gestation adversely affects offspring pancreatic beta-cell development and function.
• The timing of HFD exposure during pregnancy is critical in determining the severity of metabolic impairment in offspring.
• These findings highlight the vulnerability of fetal pancreatic development to maternal nutritional status.