Maternal High-Fat Diet Induces Long-Lasting Defects in Bone Structure in Rat Offspring Through Enhanced
Priyanka Kushwaha1, Seva G Khambadkone2,3, Mengni Li2
1Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 209, Baltimore, MD, 21205, USA.
Insights
Maternal high-fat diet (HFD) exposure during pregnancy impacts offspring bone health. Male offspring showed significant bone loss due to increased osteoclast activity, suggesting long-term skeletal health risks.
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.
Abstract:
Maternal stressors during the prenatal and perinatal periods are associated with increased susceptibility for and severity of chronic disease phenotypes in adult offspring. In this study, we used a rat model of maternal high-fat diet (HFD) exposure during pregnancy and lactation to investigate the impact on skeletal homeostasis in offspring. In the distal femur, young male and female offspring (up to 3 weeks of age) from dams fed a HFD exhibited marked increases in trabecular bone volume relative to offspring from dams fed a chow diet, but this was followed by sustained bone loss. By 15 weeks of age, male offspring of HFD fed dams exhibited a 33% reduction in trabecular bone volume fraction that histomorphometric analyses revealed was due to a nearly threefold increase in the abundance of bone-resorbing osteoclasts, while there were no differences between female control and HFD offspring by 15 weeks of age. The osteoblastic differentiation of male offspring-derived bone marrow stromal cells was not affected by maternal diet. However, osteoclastic precursors isolated from the male offspring of HFD fed dams exhibited enhanced differentiation in vitro, forming larger osteoclasts with higher expression of the fusion marker DC-STAMP. This effect appears to be mediated by a cell autonomous increase in the sensitivity of precursors to RANKL. Taken together, these results suggest that maternal stressors like HFD exposure have persistent consequences for the skeletal health of offspring that may ultimately lead to a predisposition for osteopenia/osteoporosis.
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