Maternal High-Fat Diet Induces Long-Lasting Defects in Bone Structure in Rat Offspring Through Enhanced...

Area of Science:

• Reproductive Biology
• Endocrinology
• Skeletal Biology

Background:

• Maternal stress during pregnancy and lactation can affect offspring chronic disease risk.
• High-fat diet (HFD) is a common maternal stressor with potential long-term health implications for offspring.
• Prenatal and perinatal nutrition significantly influences developmental programming and adult health outcomes.

Purpose of the Study:

• To investigate the impact of maternal high-fat diet (HFD) exposure on skeletal homeostasis in rat offspring.
• To determine sex-specific effects of maternal HFD on bone development and maintenance.
• To elucidate the cellular mechanisms underlying diet-induced skeletal changes in offspring.

Main Methods:

• Utilized a rat model with maternal HFD exposure during gestation and lactation.
• Assessed skeletal parameters in offspring at young (3 weeks) and adult (15 weeks) stages using histomorphometry.
• Isolated and cultured bone marrow stromal cells and osteoclastic precursors from offspring for in vitro differentiation assays.

Main Results:

• Maternal HFD led to transient increases in trabecular bone volume in young offspring, followed by sustained bone loss in males by 15 weeks.
• Male offspring from HFD dams exhibited significantly reduced trabecular bone volume fraction, attributed to a threefold increase in osteoclasts.
• Osteoclastic precursors from male offspring of HFD dams showed enhanced differentiation and increased sensitivity to RANKL, while osteoblastic differentiation was unaffected.

Conclusions:

• Maternal HFD exposure during critical developmental periods has persistent, sex-specific detrimental effects on offspring skeletal health.
• Increased osteoclastogenesis, driven by heightened precursor sensitivity to RANKL, is a key mechanism for HFD-induced bone loss in male offspring.
• These findings suggest that maternal dietary interventions may be crucial for preventing long-term skeletal morbidities like osteopenia and osteoporosis in offspring.