ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 2.12 | DOI: 10.1530/ey.16.2.12

Maternal Obesity and Long-term Infant Consequences

2.12. Maternal obesity impairs skeletal development in adult offspring

Chen JR, Lazarenko OP, Zhao H, Alund AW & Shankar K


To read the full abstract: J Endocrinol. 2018 Jul 26.

This study, using a mouse model, investigated the effects of high fat diet-induced maternal obesity on both fetal and adult offspring skeletal development.

Maternal nutrition appears to influence epigenetic alterations in the offspring and to program gene expression in key metabolic pathways, such as fatty acids and glucose metabolism. Maternal obesity caused by excessive consumption of a high-calorie, high-fat diet (HFD) has a profound influence on the health of cardiovascular and skeletal system of the offspring during fetal development and infancy, as well as later on in childhood and into adulthood. The relevance of epigenetic control in bone-related gene expression, bone development and organ homeostasis, as well as in the onset and progression of musculoskeletal diseases, has also been increasingly shown. Maternal obesity is known to program fetal pre-osteoblastic cell senescence signaling and glucose metabolism (Chen JR et al.).

This study, using a mouse model combined with analysis of osteoprogenitors from human obese mothers, provides evidence that maternal obesity regulates fetal osteoblastic cell senescence signaling and fetal and adult offspring skeletal development. Regardless of postnatal HFD challenge, adult offspring from HFD obese dams had suppressed bone formation. This phenomenon appeared to be much more robust in males compared to females. Such suppressed bone formation in adult offspring from HFD obese dams is a phenomenon of early bone involution/degeneration, and may be in part due to histone acetylation, (epigenetic regulation of genes involved in cell senescence signaling in pre-osteoblasts). The molecular basis of these observations seems complex and involves activation of CBP/p300 (co-activating proteins that interact with numerous transcription factors to increase the expression of their target genes) which in turn activates H3K27 acetylation (histone modification marker). This then leads to increases in cell senescence-related genes and PPARγ expression (PPARγ phosphorylation has a role in controlling bone mass) in osteogenic calvarial cells from HFD-obese dams, and in human umbilical cord mesenchymal stem cells isolated following delivery by obese and lean mothers. Thus, maternal high fat diet in mice has epigenetic effects on offspring bone formation and development.

Reference: Chen JR, Lazarenko OP, Blacbburn ML, Rose S, Frye RE, Badger TM, Andres A, Shankar K. Maternal Obesity Programs Senescence Signaling and Glucose Metabolism in Osteo-Progenitors From Rat and Human. Endocrinology 2016 Nov;157(11):4172–4183. Epub 2016 Sep 21.

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