Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2022; 14(10): 756-776
Published online Oct 26, 2022. doi: 10.4252/wjsc.v14.i10.756
Maternal inappropriate calcium intake aggravates dietary-induced obesity in male offspring by affecting the differentiation potential of mesenchymal stem cells
Ping Li, Yang Wang, Pei Li, Yuan-Lin Liu, Wei-Jiang Liu, Xiao-Yu Chen, Tian-Tian Tang, Ke-Min Qi, Yi Zhang
Ping Li, Xiao-Yu Chen, Tian-Tian Tang, Ke-Min Qi, Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children's Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
Yang Wang, Yuan-Lin Liu, Wei-Jiang Liu, Yi Zhang, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing 100085, China
Pei Li, Department of Pediatrics, General Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin 300070, China
Author contributions: Li P and Wang Y designed the study, performed the data analysis and wrote the manuscript; Li P, Chen XY and Tang TT were responsible for all the animal procedures and experiments; Liu YL and Liu WJ collected the bone mesenchymal stem cells; Qi KM and Zhang Y supervised the final manuscript.
Supported by National Natural Science Foundation of China (to P.L.), No. 81602859 and No. 82173524; and National Key Research and Development Program of China (to Y.Z.), No. 2016YFC1000305.
Institutional review board statement: This study was reviewed and approved by the institutional review board statement at Beijing Children's Hospital, Capital Medical University, National Center for Children's Health.
Institutional animal care and use committee statement: All animal studies were approved and conducted in accordance with the Beijing Academy of Military Medical Sciences Guide for the Care and Usage Committee of Laboratory Animals. Meanwhile, the animal care and use committee statement used in this study was approved on the Ethics of Animal Experiments of Academy of Military Medical Sciences in China, No. IACUC-DWZX-2019-704.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data and materials that support the findings of this study are available from the corresponding author upon the reasonable requests.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yi Zhang, MD, PhD, Professor, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No. 27 Tai-ping Road, Beijing 100085, China. zhangyi612@hotmail.com
Received: May 5, 2022
Peer-review started: May 5, 2022
First decision: June 11, 2022
Revised: June 24, 2022
Accepted: August 7, 2022
Article in press: August 7, 2022
Published online: October 26, 2022
ARTICLE HIGHLIGHTS
Research background

Obesity is characterized by the hypertrophy and hyperplasia of adipocytes, in which the commitment from bone mesenchymal stem cells (BMSCs) to preadipocytes is the important process for their hyperplasia. Our previous study showed that dietary insufficient and excessive calcium intake during pregnancy and lactation increased the body weight of offspring, using a high-fat-diet-induced obese mouse model and epidemiological cohorts. However, whether maternal inappropriate dietary calcium intake could affect the adipogenic differentiation potential of MSCs is still unclear.

Research motivation

This study was designed to investigate the effects of abnormal dietary calcium intake during gestation and lactation on the muti-differentiation potential of BMSCs among male offspring, and explore the possible role of the Wnt/β-catenin signaling pathway, which might aggravate the development of obesity, with more excessive lipid accumulation in adulthood.

Research objectives

We presented the possibility that abnormal dietary calcium intake during pregnancy and lactation could derive hyperplasic adipogenesis from BMSCs by regulating target gene expressions profiles through the fetus to adulthood among their male offspring.

Research methods

Four-week-old female C57BL/6N mice were fed by deficient, low, normal and excessive calcium reproductive diets throughout pregnancy and lactation. The BMSCs were obtained from 7-day-old male offspring to measure their adipogenic differentiation potential through the Wnt/β-catenin signaling pathway. The other weaning male pups were fed a high-fat diet for 16 wk along with a normal-fat diet as the control. Serum was collected for biochemical analysis. Adipose tissues were excised for histological examination, immunohistochemistry, determining the proportions of immune cells by flow cytometry, and gene expressions related to adipogenic differentiation and Wnt/β-catenin signaling pathway by real-time reverse transcription polymerase chain reaction.

Research results

Maternal deficient, low and excess dietary calcium intake aggravated dietary-induced obesity with more/larger adipocytes and higher serum metabolism indicators, along with disordered expressions of genes related to adipogenic differentiation (PPARγ, C/EBPα, Fabp4, LPL, Adiponectin, Resistin and Leptin) in the adipose tissues among the male offspring. We also showed significantly different expressions of similarly specific genes in BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro, respectively. The related mechanistic insights were gained to worsen this adipogenic differentiation through the Wnt/β-catenin signaling pathway in the BMSCs and adult adipose tissues.

Research conclusions

Abnormal dietary calcium intake during pregnancy and lactation might program the adipogenic differentiation potential of BMSCs among male offspring, which was related to the significantly different expressions of target genes in the Wnt/β-catenin signaling pathway to preserve more adipocytes to aggravate dietary-induced obesity in adulthood.

Research perspectives

The importance of this study is that the prevention of adulthood obesity could be moved forward to the appropriate calcium intake in the neonatal period, even the formation of maternal germ cells and fertilized egg.