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

  • Jin-Ran ChenEmail author
Reference work entry

Abstract

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.

Keywords

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

List of Abbreviations

AMP

5′ adenosine monophosphate-activated protein kinase

BB

Blueberry

BMC

Bone mineral content

BMD

Bone mineral density

CBP

CREB-binding protein

DNMTs

DNA methyltransferases

E15.5

Embryos on day 15.5 of gestation

ECOCs

Embryonic calvarial osteoblastic cells

EGR1

Early growth response 1

Ezh2

Enhancer of zeste homolog 2

GNATs

Gcn5-related N-acetyltransferases

H3K27

Lysine 27 in histone H3

HATs

Histone acetyltransferases

HDACs

Histone deacetylases

HDACs

Histone deacetylases

HFD

High fat diet

Hox

Homeobox

IL-6

Interleukin-6

IRF8

Interferon regulatory factor 8

IRS

Insulin receptor substrates

MSCs

Mesenchymal stem cells

NEFA

Non-esterified free fatty acids

PA

Phenolic acids

PDK-1

Phosphatidylinositol phosphate-dependent kinase-1

PI3K

Phosphoinositide 3-kinase

PIP2

Phosphatidylinositol 4,5-bisphosphate

PKB

Protein kinase B

PPARγ

Peroxisome proliferator-activated receptor γ

PPRE

Peroxisome proliferator responsive element

Runx2

The runt domain-containing transcription factor

SATB2

Special AT-rich sequence-binding protein 2

SAβG

Senescence-associated β-galactosidase

UC

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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