Differences in Neuregulin 4 Expression in Children: Effects of Fat Depots and Obese Status

ABSTRACT

Purpose

To observe the expression of Nrg4, uncoupling protein-1 (UCP1), tumor necrosis factor α (TNFα), CD31, VE-cadherin/CDH5 and vascular endothelial growth factor A (VEGF-A) mRNA in abdominal subcutaneous (SC), omental (OM) adipose tissue in children with relation to anthropometric parameters. Further to verify the effect of inflammatory mediators on Nrg4 and UCP1 mRNA expression in adipocytes.

Methods

Paired SC and OM adipose tissues were obtained from 58 children. In vitro, the adipocytes isolated from primary inguinal adipose tissue of mice were treated with TNFα (50 ng/ml) for 12–48 h. mRNA levels of Nrg4, UCP1 and TNFα were determined by real-time PCR.

Results

Nrg4, UCP1, VEGF-A and CDH5 mRNA levels in SC were significantly higher than those in OM adipose tissue and the mRNA level of TNFα showed the opposite result. Moreover, Nrg4 and UCP1 mRNA in SC were significantly lower in overweight children compared to normal weight children. Nrg4 in SC and OM was negatively associated with BMISDS, WHtR. CDH55 mRNA in OM was negatively associated with WHR. VEGF-A was positively correlated with Nrg4 in SC. In vitro, Nrg4 and UCP1 mRNA levels in adipocytes were dose- and time-dependently decreased under TNFα treatment.

Conclusions

Nrg4, UCP1, VEGF-A and CDH5 mRNA expression in adipose tissues display a depot-specific pattern. Nrg4 mRNA levels in adipose tissue are decreased with obesity and associated with WAT browning and angiogenesis. TNFα may be involved in the regulation of Nrg4 level in adipose tissue, which may be one of the causes of the down-regulation of Nrg4 expression in obesity with chronic inflammatory response.

KEYWORDS:

• Adipose tissue depots
• children
• overweight
• Neuregulin 4

Compliance with ethical standardsConflict of Interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical Approval

All procedures performed in the study involving human participants were in accordance with ethical standards of Children’s Hospital of Nanjing Medical University Ethical Committee.

Informed Consent

Informed consent was obtained from all individual participants or their parents included in the study.

Additional information

Funding

The study was founded by National Natural Science Foundation of China [Grant/Award Number: 81273064 and81773421]; Jiangsu Provincial key research and development program [Grant/Award Number: BE2015607]; and Innovation Team of Jiangsu Health [Grant/Award Number: CXTDA2017035].