Biomedical subjects

M W Huff

Publications and source records attributed to M W Huff.

76 records · Page 5Linked to original sources

PubMedDate not supplied

Cholesterol accumulation in J774 macrophages induced by triglyceride-rich lipoproteins. Comparison of very low density lipoprotein from subjects with type III, IV, and V hyperlipoproteinemias.

The capacity of human triglyceride-rich lipoproteins to induce cholesterol accumulation in the murine J774 macrophage cell line was investigated with large very low density lipoprotein (VLDL, Sf 60-400) obtained from subjects with type III, IV, and V hyperlipoproteinemias. After incubation for 24 hours, VLDLs from type IV and type V subjects were similar in their ability to raise cellular cholesterol deposition threefold to fourfold and cellular triglyceride 16-fold. The increase in cholesterol was entirely due to the dramatic increase in cholesterol ester, from less than 1 to greater than 50 micrograms/mg cell protein. Total cholesterol accumulation was fourfold to fivefold greater than the cholesterol accumulation observed for VLDL or low density lipoprotein (LDL) from normal subjects. Cholesterol esterification (acyl coenzyme A: cholesterol acyltransferase [ACAT] activity) paralleled the rate of cholesterol accumulation in these cells. Treating the macrophages with the ACAT inhibitor 58035, which is known to downregulate the LDL receptor in these cells, diminished cholesterol accumulation by 40% for type IV VLDL and by 23% for normal LDL. Since hypertriglyceridemic VLDL carries excess apoprotein (apo) E molecules, we investigated the role of normal and abnormal apo E. An anti-apo E monoclonal antibody, known to block the binding of apo E to the LDL receptor, blocked type IV VLDL-induced cholesterol ester accumulation by approximately 70%. In contrast to type IV subjects, VLDL from type III subjects (homozygous for apo E2) when incubated with J774 macrophages (which do not secrete apo E) caused only a modest 1.5-2-fold increase in cellular cholesterol. Pre-beta- and beta-migrating VLDL subfractions from type III subjects were equally ineffective in causing cholesterol accumulation. By contrast, beta-VLDL from cholesterol-fed rabbits caused a sevenfold to eightfold increase in cellular cholesterol content. These results indicate that triglyceride-rich lipoproteins from type IV and type V subjects can cause substantial cholesterol ester accumulation and enhanced cholesterol esterification in J774 cells. The lower cholesterol accumulation with type IV VLDL in the presence of apo E antibodies and VLDL from type III subjects demonstrates the importance of functional apo E in this process.

Animals↗

PubMedDate not supplied

Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis.

The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Dietary fish oil increases conversion of very low density lipoprotein apoprotein B to low density lipoprotein.

Dietary fish oils, which are rich in omega-3 fatty acids, are known to produce a marked lowering of very low density lipoprotein (VLDL) triglyceride concentrations, but they have a less marked effect on low density lipoprotein (LDL) cholesterol. Our previous apolipoprotein (apo) B kinetic studies in miniature pigs demonstrated that conversion of VLDL apo B to LDL apo B accounted for 15% to 20% of total VLDL apo B catabolism. In addition, 75% to 80% of LDL apo B was derived independent of plasma VLDL or intermediate density lipoprotein (IDL) apo B catabolism. The present studies were carried out to determine if fish-oil diets influenced: 1) the conversion of VLDL to LDL, and 2) the pathways of LDL apo B synthesis. Autologous 125I-VLDL and 131I-LDL were injected into four pigs after both a corn-oil (30 g/day for 18 days) and a Maxepa (30 g/day for 18 days) dietary period. Analysis of apo B specific activity curves demonstrated that fish oil reduced the VLDL pool size by 38% (p less than 0.05) due to an increase in fractional catabolic rate (0.83 +/- 0.13 vs. 0.48 +/- 0.03 hr-1), as the synthesis rate was unaffected. However, the proportion of VLDL apo B converted to LDL increased significantly (56 +/- 7% vs. 17 +/- 3%, p less than 0.01) whereas the proportion cleared directly decreased (46 +/- 5% vs. 83 +/- 3%, p less than 0.005). Fish oil reduced total LDL apo B synthesis (0.6 +/- 0.1 vs. 1.1 +/- 0.2 mg/hr/kg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

An apolipoprotein CII mutation, CIILys19----Thr' identified in patients with hyperlipidemia.

Five hyperlipidemic patients (one with Type III, three with Type IV, and one with Type V hyperlipoproteinemia) were found on isoelectric focusing to have both the normal isoform of apolipoprotein CII and a second isoform whose isoelectric point was consistent with a single charge change. The structure of the apolipoprotein CII variant was determined to be the same as normal apolipoprotein CII except for replacement of the normal Lys at amino acid residue 19 by Thr (C2K19T). The mutation was absent from 160 apoCII alleles screened from normolipemic subjects. The C2K19T substitution occurs in a domain of apolipoprotein CII postulated to contain a lipid-binding amphipathic alpha-helix. The presence of C2K19T in unrelated hyperlipidemic patients of various racial backgrounds suggests that, in combination with other factors such as mutations in apolipoprotein E, it plays a role in the development of hyperlipoproteinemias.

Adult↗