Cytosolic lipid trafficking proteins STARD4 and STARD5 modulate hepatic neutral lipid metabolism: implications for diabetic dyslipidaemia and steatosis

Ugo Soffientini, Sharron Dolan, Annette Graham*

*Corresponding author for this work

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Abstract

This study explored expression of the START domain family in hyperinsulinaemic, genetically obese rodents, and the functional roles of cytosolic StarD4 and StarD5 proteins in hepatic lipid synthesis and export. Genetic obesity in (fa/fa) Zucker rats repressed StarD4, StarD5, StarD8 and StarD13, and decreased levels of cytosolic StarD4 and StarD5 proteins, compared with lean controls, suggesting links with hepatic storage or secretion of lipids.
Stable overexpression of STARD4 in rat McArdle RH7777 hepatoma cells increased lipidation of exogenous ApoA-I compared with empty vector (EV) control, modestly increased secretion of endogenously synthesized cholesterol
and reduced incorporation of [14C]oleate into cellular cholesteryl esters. Synthesis and secretion of triacylglycerol did not change in STARD4 overexpressing cells. By contrast, STARD5 overexpression did not alter cholesterol synthesis, secretion, or lipidation of apoA-I, but increased synthesis of triacylglycerol from [3 H]glycerol under basal conditions, enhanced incorporation of [14C]oleate into triacylglycerol, and increased expression of Dgat1 and Dgat2 compared with EV.
In summary, cytosolic STARD4 impacts predominantly on cholesterol efflux to apoA-I, implying directional transport of cholesterol to the plasma membrane, while STARD5 increases basal triacylglycerol synthesis and enriches this pool with exogenous fatty acids. Cytosolic StarD proteins may be involved in diabetic dyslipidaemia and steatosis.
Original languageEnglish
Article number1000558
JournalJournal of Diabetes and Metabolism
Volume6
Issue number6
DOIs
Publication statusPublished - 30 May 2015

Keywords

  • cell signalling
  • lipid metabolism
  • diabetes

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