High-Fat Diet and Maternal Obesity-Associated Epigenetic Regulation of Bone Development

  • Jin-Ran ChenEmail author
Reference work entry


Due to the worldwide epidemic in obesity, maternal obesity has recently seen an explosion in investigations in both animal models and humans on its effects on offspring phenotype and pathologies including diabetes, hyperlipidemia, cardiovascular disease, and cancer. Epigenetic mechanisms presumably explain how metabolic or nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases. Developmental programming and epigenetic regulation of the fetal skeletal development associated with maternal obesity and diet is understudied. The fetal and neonatal bone cells represent potential targets for developmental programming. Maternal obesity-associated epigenetically regulated events in utero contributes toward changes in the ability to attain peak bone mass and increases in risk of the adult onset of degenerative bone disorders. Recent studies in rodents showed that the embryonic/neonatal skeletal phenotype can be programmed by maternal high fat/high sugar obesity-promoting diets prior to and during pregnancy. Importantly, evidence from a human study suggested that umbilical cord mesenchymal stem cells (UC-MSCs) from obese mothers have less potential to differentiate toward osteoblast, and more potential for adipogenesis. Further research on the mechanisms connecting maternal obesity, fetal bone development, and postnatal bone formation are required.


Obesity High fat diet Bone development Epigenetic DNA methylation Osteoblast senescence Nutrition 

List of Abbreviations


5′ adenosine monophosphate-activated protein kinase




Bone mineral content


Bone mineral density


CREB-binding protein


DNA methyltransferases


Embryos on day 15.5 of gestation


Embryonic calvarial osteoblastic cells


Early growth response 1


Enhancer of zeste homolog 2


Gcn5-related N-acetyltransferases


Lysine 27 in histone H3


Histone acetyltransferases


Histone deacetylases


Histone deacetylases


High fat diet






Interferon regulatory factor 8


Insulin receptor substrates


Mesenchymal stem cells


Non-esterified free fatty acids


Phenolic acids


Phosphatidylinositol phosphate-dependent kinase-1


Phosphoinositide 3-kinase


Phosphatidylinositol 4,5-bisphosphate


Protein kinase B


Peroxisome proliferator-activated receptor γ


Peroxisome proliferator responsive element


The runt domain-containing transcription factor


Special AT-rich sequence-binding protein 2


Senescence-associated β-galactosidase


Umbilical cord


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Authors and Affiliations

  1. 1.Arkansas Children’s Nutrition Center and the Department of PediatricsUniversity of Arkansas for Medical SciencesLittle RockUSA

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