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
Processing time: 173 Days and 1.4 Hours
Abstract
BACKGROUND

The effects of inappropriate dietary calcium intake in early life on later obesity have not been fully elucidated.

AIM

To raise the mechanism of maternal calcium intake on the multi-differentiation potential of mesenchymal stem cells among their male offspring.

METHODS

Four-week-old female C57BL/6N mice were fed by deficient, low, normal and excessive calcium reproductive diets throughout pregnancy and lactation. Bone MSCs (BMSCs) were obtained from 7-day-old male offspring to measure the adipogenic differentiation potential by the Wnt/β-catenin signaling pathway. The other weaning male pups were fed a high-fat diet for 16 wk, along with normal-fat diet as the control. Then the serum was collected for the measurement of biochemical indicators. Meanwhile, the adipose tissues were excised to analyze the adipocyte sizes and inflammatory infiltration. And the target gene expressions on the adipogenic differentiation and Wnt/β-catenin signaling pathway in the adipose tissues and BMSCs were determined by real-time reverse transcription polymerase chain reaction.

RESULTS

Compared with the control group, maternal deficient, low and excessive calcium intake during pregnancy and lactation aggravated dietary-induced obesity, with larger adipocytes, more serious inflammatory infiltration and higher serum metabolism indicators by interfering with higher expressions of adipogenic differentiation (PPARγ, C/EBPα, Fabp4, LPL, Adiponectin, Resistin and/or Leptin) among their male offspring (P < 0.05). And there were significantly different expression of similar specific genes in the BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro, respectively (P < 0.05). Meanwhile, it was accompanied by more significant disorders on the expressions of Wnt/β-catenin signaling pathway both in BMSCs and adulthood adipose tissues among the offspring from maternal inappropriate dietary calcium intake groups.

CONCLUSION

Early-life abnormal dietary calcium intake might program the adipogenic differentiation potential of BMSCs from male offspring, with significant expressions on the Wnt/β-catenin signaling pathway to aggravate high-fat-diet-induced obesity in adulthood.

Keywords: Calcium; Obesity; Bone mesenchymal stem cells; Wnt/β-catenin signaling pathway; Adipogenic differentiation; Male offspring

Core tip: Maternal inappropriate dietary calcium intake could aggravate high-fat-diet-induced obesity among male offspring, with larger adipocytes and more serious inflammatory infiltration by interfering with the higher expressions of adipogenic genes, which was accompanied by significant expressions of specific genes on the adipogenic and osteogenic differentiation. It was worsened by the disorders of Wnt/β-catenin signaling pathway both in the BMSCs and adipose tissues. So the importance of this study was 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.