Maternal high-cholesterol diet negatively programs offspring bone development and downregulates hedgehog signaling in osteoblasts.

Autor:	Mangu SR; Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysuru, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India., Patel K; Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysuru, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India., Sukhdeo SV; Department of Meat and Marine Sciences, CSIR-Central Food Technological Research Institute, Mysuru, India., Savitha MR; Department of Paediatrics, Mysore Medical College and Research Institute, Mysuru, India., Sharan K; Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysuru, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India. Electronic address: kunalsharan@cftri.res.in.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2022 Sep; Vol. 298 (9), pp. 102324. Date of Electronic Publication: 2022 Aug 02.
DOI:	10.1016/j.jbc.2022.102324
Abstrakt:	Cholesterol is one of the essential intrauterine factors required for fetal growth and development. Maternal high cholesterol levels are known to be detrimental for offspring health. However, its long-term effect on offspring skeletal development remains to be elucidated. We performed our studies in two strains of mice (C57BL6/J and Swiss Albino) and human subjects (65 mother-female newborn dyads) to understand the regulation of offspring skeletal growth by maternal high cholesterol. We found that mice offspring from high-cholesterol-fed dams had low birth weight, smaller body length, and delayed skeletal ossification at the E18.5 embryonic stage. Moreover, we observed that the offspring did not recover from the reduced skeletal mass and exhibited a low bone mass phenotype throughout their life. We attributed this effect to reduced osteoblast cell activity with a concomitant increase in the osteoclast cell population. Our investigation of the molecular mechanism revealed that offspring from high-cholesterol-fed dams had a decrease in the expression of ligands and proteins involved in hedgehog signaling. Further, our cross-sectional study of human subjects showed a significant inverse correlation between maternal blood cholesterol levels and cord blood bone formation markers. Moreover, the bone formation markers were significantly lower in the female newborns of hypercholesterolemic mothers compared with mothers with normal cholesterolemic levels. Together, our results suggest that maternal high cholesterol levels deleteriously program offspring bone mass and bone quality and downregulate the hedgehog signaling pathway in their osteoblasts. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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