TY - JOUR
T1 - Maternal High-Fat Diet Induces Long-Lasting Defects in Bone Structure in Rat Offspring Through Enhanced Osteoclastogenesis
AU - Kushwaha, Priyanka
AU - Khambadkone, Seva G.
AU - Li, Mengni
AU - Goodman, Ethan J.
AU - Aravindan, Nandini
AU - Riddle, Ryan C.
AU - Tamashiro, Kellie L.K.
N1 - Funding Information:
The funding was supported by National Institutes of Health (Grant Nos. HD093338 and MH108944), National Institute of Diabetes and Digestive and Kidney Diseases (Grant No. DK099134) and U.S. Department of Veterans Affairs (Grant No. BX003742).
Funding Information:
The authors are grateful to Marie-Claude Faugere for assistance with histomorphometric analyses. The studied in this manuscript were supported by NIH HD093338 (S. G. K.), NIH DK099134 (R. C. R), VA BX003742 (R.C.R), and NIH MH108944 (K. L. K. T.)
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - Bone
KW - Developmental origins of health and disease
KW - Maternal diet
KW - Osteoclast
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U2 - 10.1007/s00223-020-00801-4
DO - 10.1007/s00223-020-00801-4
M3 - Article
C2 - 33386478
AN - SCOPUS:85098478832
VL - 108
SP - 680
EP - 692
JO - Calcified Tissue International
JF - Calcified Tissue International
SN - 0171-967X
IS - 5
ER -