Maternal Hyperleptinemia Is Associated with Male Offspring's Altered Vascular Function and Structure in Mice

Area of Science:

• Reproductive biology
• Vascular physiology
• Developmental origins of health and disease

Background:

• Gestational diabetes mellitus (GDM) and obesity increase maternal leptin levels.
• Offspring of mothers with GDM face higher risks of hypertension and cardiovascular issues.
• Mechanisms linking maternal hyperleptinemia to offspring vascular dysfunction remain unclear.

Purpose of the Study:

• To investigate the impact of maternal hyperleptinemia on offspring blood pressure, vascular structure, and function.
• To determine if maternal hyperleptinemia alters offspring vascular responses to diet and age.

Main Methods:

• Utilized a mouse model with hyperleptinemic (Leprdb/+) and control (WT) dams.
• Assessed vascular function and structure in male offspring at 6 and 31 weeks of age.
• Exposed half of the offspring to a high-fat, high-sucrose diet (HFD) for 6 weeks.

Main Results:

• Maternal hyperleptinemia led to outwardly remodeled mesenteric arteries and enhanced insulin vasodilation in offspring on a standard diet.
• High-fat, high-sucrose diet (HFD) increased blood pressure and induced vessel hypertrophy in control offspring but not in offspring of hyperleptinemic dams.
• HFD reduced insulin responsiveness in offspring of hyperleptinemic dams, while arteries remained stiffer regardless of diet.

Conclusions:

• Maternal hyperleptinemia has differential effects on offspring vascular health depending on diet.
• While protective under standard conditions, maternal hyperleptinemia exacerbates negative vascular changes in offspring fed a HFD.
• Findings suggest maternal leptin interacts with environmental factors to influence offspring vascular outcomes in pregnancies complicated by GDM or obesity.