PubMed1978
High carbohydrate (CHO) diets cause accumulation in plasma of larger, triglyceride (TG)-enriched very low density lipoprotein (VLDL) particles. In man, the composition of the VLDL is changed by such diets as well. The source of the altered VLDL particles is presumed to be the liver, but the intestine is known to secrete VLDL, and VLDL is also altered during its postsecretory catabolism. To ascertain that the liver is a source of "diet-induced VLDL," we fed rats CHO and control diets and we examined plasma levels of lipids chemically and apoproteins A-I (ApoA-I) and B (ApoB) by specific radioimmunoassay (RIA). VLDL (d less than 1.006) and VLDL density subfractions were isolated and their composition studied by RIA, column chromatography, isoelectric focusing (IEF), and polyacrylamide gel electrophoresis. Livers from control and CHO-fed rats were perfused in vitro. Whole perfusates and perfusate VLDL were studied similary. In the CHO-fed rats, plasma TG increased, cholesterol and ApoA-I remained unchanged, and ApoB fell. The VLDL isolated were TG enriched and less dense. Although total VLDL-protein rose, the proportion of VLDL-protein that was ApoB and arginine-rich protein (ARP) fell, while ApoC rose. The ApoB content varied directly with density of particles. ARP subunits were not changed, but relative proportions of ApoC-III0 rose from 39 to 46 per cent of dye uptake on IEF gels and ApoC-III3 fell from 34 to 26 per cent. Thus, CHO feeding produced altered plasma VLDL in the rat. The perfused livers of the CHO-fed rat secreted more TG, but absolute secretory rates for cholesterol, ApoB, and ApoA-I were unchanged. The VLDL isolated from perfusates were larger, TG-enriched, and less dense. Although VLDL-protein rose, the proportion that was ApoB fell; both ApoC and ARP rose, ARP subunits were unchanged, while ApoC-III0 rose from 29 to 37 per cent and ApoC-III3 fell from 48 to 42 per cent. In contrast to plasma, ApoC content was not increased relative to ARP. As in plasma, content of ApoB varied with particle density. Thus, CHO feeding induced changes in hepatic perfusate VLDL structure and composition that in general paralleled those changes seen in plasma. This strongly suggests that the action of diet on the liver is responsible for many of the changes seen in plasma VLDL. On the other hand, the discrepancy between the VLDL-ApoC content and subunit proportions of plasma and perfusate suggests that the discrepancy is due to postsecretory processing. Similarly, the failure to see decreases in absolute hepatic ApoB secretion, while plasma ApoB levels fell, suggests that the postsecretory metabolism of ApoB-containing lipoproteins is also altered by diet. In addition, the failure to see increases in hepatic VLDL-ApoB secretory rates at a time when VLDL-TG and VLDL-protein increased suggests that there is no tight coupling between the secretion of ApoB and lipids.