Maternal loading with very low-density lipoproteins stimulates fetal surfactant synthesis.
We examined whether administration of very low-density lipoproteins (VLDL) to pregnant rats increases surfactant phosphatidylcholine (PtdCho) content in fetal pre-type II alveolar epithelial cells. VLDL-triglycerides are hydrolyzed to fatty acids by lipoprotein lipase (LPL), an enzyme activated by heparin. Fatty acids released by LPL can incorporate into the PtdCho molecule or activate the key biosynthetic enzyme cytidylyltransferase (CCT). Dams were given BSA, heparin, VLDL, or VLDL with heparin intravenously. Radiolabeled VLDL given to the pregnant rat crossed the placenta and was distributed systemically in the fetus and incorporated into disaturated PtdCho (DSPtdCho) in pre-type II cells. Maternal administration of VLDL with heparin increased DSPtdCho content in cells by 45% compared with control (P < 0.05). VLDL produced a dose-dependent, saturable, and selective increase in CCT activity. VLDL did not significantly alter immunoreactive CCT content but increased palmitic, stearic, and oleic acids in pre-type II cells. Furthermore, hypertriglyceridemic apolipoprotein E knockout mice contained significantly greater levels of DSPtdCho content in alveolar lavage and CCT activity compared with either LDL receptor knockout mice or wild-type controls that have normal serum triglycerides. Thus the nutritional or genetic modulation of serum VLDL-triglycerides provides specific fatty acids that stimulate PtdCho synthesis and CCT activity thereby increasing surfactant content.
Department of Internal Medicine and the Department of Veterans Affairs Medical Center, The University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Alan J
AJ
Ryan
Jheem D
JD
Medh
Diann M
DM
McCoy
Ronald G
RG
Salome
Rama K
RK
Mallampalli
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D015151:Immunoblotting; D007275:Injections, Intravenous; D008079:Lipoproteins, VLDL / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008168:Lung / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000235:genetics
D001057:Apolipoproteins E; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D011973:Receptors, LDL; C017463:lecithins, disaturated; D019916:Choline-Phosphate Cytidylyltransferase