Embryonic cholesterol esterification is regulated by a cyclic AMP-dependent pathway in yolk sac membrane-derived endodermal epithelial cells

PLoS One. 2017 Nov 21;12(11):e0187560. doi: 10.1371/journal.pone.0187560. eCollection 2017.

Abstract

During avian embryonic development, endodermal epithelial cells (EECs) absorb yolk through the yolk sac membrane. Sterol O-acyltransferase (SOAT) is important for esterification and yolk lipid utilization during development. Because the major enzyme for yolk sac membrane cholesteryl ester synthesis is SOAT1, we cloned the avian SOAT1 promoter and elucidated the cellular functions of SOAT1. Treatments with either glucagon, isobutylmethylxanthine (IBMX), an adenylate cyclase activator (forskolin), a cAMP analog (dibutyryl-cAMP), or a low glucose concentration all increased SOAT1 mRNA accumulation in EECs from Japanese quail, suggesting that SOAT1 is regulated by nutrients and hormones through a cAMP-dependent pathway. Activity of protein kinase A (PKA) was increased by IBMX, whereas co-treatment with the PKA inhibitor, H89 negated the increase in PKA activity. Cyclic AMP-induced EECs had greater cholesterol esterification than untreated EECs. By promoter deletion and point-mutation, the cAMP-response element (-349 to -341 bp) was identified as critical in mediating transcription of SOAT1. In conclusion, expression of SOAT1 was regulated by a cAMP-dependent pathway and factors that increase PKA will increase SOAT1 to improve the utilization of lipids in the EECs and potentially modify embryonic growth.

MeSH terms

  • Animals
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cholesterol / metabolism*
  • Cholesterol Esters / genetics
  • Cholesterol Esters / metabolism*
  • Coturnix / embryology*
  • Coturnix / genetics
  • Cyclic AMP / metabolism
  • Embryonic Development / genetics*
  • Endoderm / growth & development
  • Endoderm / metabolism
  • Epithelial Cells / metabolism
  • Esterification / genetics
  • Glucagon / metabolism
  • Hepatocytes / metabolism
  • Promoter Regions, Genetic
  • Sterol O-Acyltransferase / metabolism
  • Yolk Sac / growth & development
  • Yolk Sac / metabolism

Substances

  • Cholesterol Esters
  • Glucagon
  • Cholesterol
  • Cyclic AMP
  • Sterol O-Acyltransferase

Grants and funding

This work was supported by the Ministry of Science and Technology, under Grant 104-2313-B-002-039-MY3 in Taiwan to Shih-Torng Ding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.