Chylomicron synthesis in experimental nephrotic syndrome.
Mesenteric lymph was collected for 48 h from rats with aminonucleoside-induced nephrotic syndrome, receiving an intraduodenal infusion of a triacylglycerol emulsion. In nephrosis, the rates of lymph flow and triacylglycerol transport were approx. 2-fold higher, but the transport of total protein and of apoproteins A-I and E was 2- to 3-fold lower than that in control rats, resulting in chylomicrons with a 3-fold approx. elevated triacylglycerol/protein ratio. Supplementation of the triacylglycerol infusate with glucose and amino acids did not increase the protein or apoA-I and apoE transport. Production or transport of B and C apoproteins in nephrotic rats was also reduced, as indicated by tetramethylurea solubility, incorporation of intraduodenally infused [3H]leucine and staining of the chylomicron proteins on SDS-PAGE gels. Apoprotein A-IV was the only chylomicron component into which the leucine incorporation was elevated, but its relative content was not increased on SDS-PAGE gels. Lymph chylomicrons of nephrotic rats were larger in size (1498 +/- 37 vs. 1235 +/- 23 A), consistent with the higher triacylglycerol/protein ratio. The concentration of all lipoprotein classes was markedly elevated in the plasma of nephrotic rats, as was that of the total A-I and E apoproteins. Intravenous injection of 125I-labelled HDL, followed by tracing of the label in lymph chylomicrons, indicated a lower rate of transfer of HDL apoproteins from plasma to lymph in nephrotic rats. We conclude that the intestinal chylomicron formation in nephrosis is characterised by an enhanced triacylglycerol transport without the appropriate apoprotein complement. This is probably due to the limited capacity of enterocytes, in marked contrast to hepatocytes, to respond to the hypoproteinemia of nephrosis with increased production and/or transport of the apoproteins.
Department of Biochemistry, Hadassah University Hospital, Jerusalem, Israel.
E
E
Levy
E
E
Ziv
H
H
Bar-On
E
E
Shafrir
D000818:Animals; D001053:Apolipoproteins / Q000096:biosynthesis; D002914:Chylomicrons / Q000096:biosynthesis* / Q000097:blood / Q000648:ultrastructure; D004195:Disease Models, Animal; D008074:Lipoproteins / Q000097:blood; D008196:Lymph / Q000032:analysis; D008297:Male; D008855:Microscopy, Electron, Scanning; D009404:Nephrotic Syndrome / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001053:Apolipoproteins; D002914:Chylomicrons; D008074:Lipoproteins