Maternal Retinoids Increase PDGFRα+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development

• Published in: EBioMedicine Vol. 18; no. C; pp. 288 - 299
• Main Authors: Wang, Bo, Fu, Xing, Liang, Xingwei, Wang, Zhixiu, Yang, Qiyuan, Zou, Tiande, Nie, Wei, Zhao, Junxing, Gao, Pengfei, Zhu, Mei-Jun, de Avila, Jeanene M., Maricelli, Joseph, Rodgers, Buel D., Du, Min
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2017; Elsevier
• Subjects: Adipogenesis - drug effects; Adipose development; Adipose Tissue, Beige - cytology; Adipose Tissue, Beige - metabolism; Adipose Tissue, Beige - pathology; Animals; Beige adipocyte; Body Temperature; Cells, Cultured; Chromatography, High Pressure Liquid; Diet, High-Fat; Dietary Supplements; Female; Glucose Tolerance Test; Male; Maternal care; Mice; Mice, Inbred C57BL; Obesity - pathology; Obesity - prevention & control; Oxygen Consumption - drug effects; Pregnancy; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Research Paper; Retinaldehyde - blood; Retinoic acid; Signal Transduction - drug effects; Stromal Cells - cytology; Stromal Cells - drug effects; Stromal Cells - metabolism; Tretinoin - blood; Tretinoin - pharmacology; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vasculature; Vitamin A; Vitamin A - blood; Vitamin A - pharmacology; Vitamin A; Maternal care; Adipose development; Retinoic acid; Beige adipocyte; Vasculature
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2017.03.041

Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα+ adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA. Furthermore, RA-induced beige adipogenesis was blocked following vascular endothelial growth factor receptor (VEGFR) 2 knock out in PDGFRα+ cells, suggesting its mediatory role. Our data reveal an intrinsic link between maternal retinoid level and offspring health via promoting beige adipogenesis. Thus, enhancing maternal retinoids is an amiable therapeutic strategy to prevent obesity in offspring, especially for those born to obese mothers which account for one third of all pregnancies. •Maternal vitamin A supplementation increases blood vessel density and expands adipose progenitor population in progeny.•Maternal vitamin A supplementation enhances brown-like phenotype in adipose tissues.•Maternal vitamin A supplementation protects offspring from diet induced obesity. Vitamin A and its metabolite, retinoic acid, play key roles in adipogenesis and energy expenditure of adipose tissues. In mice and humans, vitamin A intake is inversely correlated with adiposity. This study has uncovered a role for maternal retinoids in fetal adipose development. Maternal vitamin A supplementation or RA administration increases adipose progenitor population and promotes beige adipogenesis, which protects offspring from diet induced obesity in later life.