Dataset Information

Maternal Retinoids Increase PDGFR?⁺ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development.

ABSTRACT: 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 PDGFR?⁺ 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 (RAR?DN) 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 PDGFR?⁺ 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.

SUBMITTER: Wang B

PROVIDER: S-EPMC5405191 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Maternal Retinoids Increase PDGFRα<sup>+</sup> Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development.

Wang Bo B Fu Xing X Liang Xingwei X Wang Zhixiu Z Yang Qiyuan Q Zou Tiande T Nie Wei W Zhao Junxing J Gao Pengfei P Zhu Mei-Jun MJ de Avila Jeanene M JM Maricelli Joseph J Rodgers Buel D BD Du Min M

EBioMedicine 20170404

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<sup>+</sup> 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 increas ...[more]

PMID: 28408241

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Project description:BACKGROUND:Recent studies suggest human neck brown adipose tissue (BAT) to consist of 'brown adipocyte (BA)-like' or beige adipocytes. However, little is known about their thermogenic function. Within the beige adipocyte transcriptome, fibroblast growth factor-21 (FGF21) is a gene whose protein product acts as an adipokine, regulating cold-induced thermogenesis in animals. Here, we explored (i) the adipogenic potential, thermogenic function and FGF21 secretory capacity of beige adipocytes derived from human neck fat and (ii) the role of FGF21 in modulating adipose bioenergetics. METHODS:Progenitors isolated from human cervical fat were differentiated into adipocytes with either a BA-like or white adipocyte (WA) phenotype. FGF21 secretion was measured by enzyme-linked immuosorbent assay. Real-time PCR/western blotting was used to determine cellular mRNA/protein levels. Extracellular flux bioanalyzer was used to quantify adipocyte oxygen consumption and fatty acid oxidation. Adipocyte heat production was measured by infrared thermography. RESULTS:Under hormonal manipulation, primary human neck pre-adipocytes differentiated into adipocytes with either BA-like or WA phenotypes, on gene/protein and functional levels. BA-like cells expressed beige but not classic BA markers. During BA differentiation, FGF21 gene expression and secretion were increased, and were augmented following norepinephrine exposure (a cold mimic in vitro). Differentiated WA expressed ?-klotho, a critical co-factor mediating FGF21 action. Treatment of WA with FGF21-induced UCP1 expression and increased oxygen consumption, respiratory uncoupling, norepinephrine-mediated thermogenesis, fatty acid oxidation and heat production, thus recapitulating the association between cold-induced FGF21 secretion and cold-induced thermogenesis in vivo. CONCLUSION:Beige adipocytes are thermogenic in humans. FGF21 is a beige adipokine capable of promoting a brown fat-like thermogenic program in WAs. SIGNIFICANCE:This study provides first evidence of inducible functional thermogenic beige adipogenesis in human neck fat. FGF21 holds promise as a cold-induced beige adipokine with metabolic benefits of therapeutic relevance through browning of white adipose tissue.

Dataset Information

Maternal Retinoids Increase PDGFR?⁺ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development.

Publications

Maternal Retinoids Increase PDGFRα<sup>+</sup> Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development.

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Dataset Information

Maternal Retinoids Increase PDGFR?+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development.

Publications

Maternal Retinoids Increase PDGFRα<sup>+</sup> Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Maternal Retinoids Increase PDGFR?⁺ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development.