0
May 18, 1984, Vol 251, No. 19 >
ARTICLE | May 18, 1984

Dual Defect in Metabolism of Very-Low-Density Lipoprotein Triglycerides: Title and subTitle BreakPatients With Type 5 Hyperlipoproteinemia FREE

Y. Antero Kesaniemi, MD; Scott M. Grundy, MD, PhD
[+] Author Affiliations

Reprint requests to Center for Human Nutrition (G4-100), University of Texas Health Science Center, 5323 Harry Hines Blvd, Dallas, TX 75235 (Dr Grundy).


JAMA. 1984;251(19):2542-2547. doi:10.1001/jama.1984.03340430040026
Text Size: A A A
Published online
Article
References

Transport of very-low-density lipoprotein (VLDL) triglycerides (TGs) were studied in eight patients with type 5 hyperlipoproteinemia (HLP). Results were compared to those from patients with type 4 HLP. Type 4 patients had either overproduction of VLDL TGs (nine patients) or defective clearance of VLDL TGs (eight patients). Patients with type 5 HLP were found to have increased production rates of VLDL TG, but also reduced fractional catabolic rates of VLDL TGs. Synthesis rates of VLDL TGs in type 5 were similar to those in type 4 patients with overproduction of VLDL TGs. The mean fractional catabolic rate in patients with type 5 HLP also were similar to those of type 4 patients with defective clearance. This study demonstrates that in most patients with type 5 HLP there is a dual defect in TG metabolism—overproduction of VLDL TGs and a clearance defect for TG-rich lipoproteins.

(JAMA 1984;251:2542-2547)

REFERENCES

1 +
Fredrickson DS, Lees RS:  A system for phenotyping hyperlipoproteinemia . Circulation 1965;;31:321-327.
2 +
Kissebah AH, Adams PW, Harrigan P, et al:  The mechanism of action of clofibrate and tetranicotinolyfructose (Bradilan) on the kinetics of plasma free fatty acid and triglyceride transport in type IV and type V hypertriglyceridaemia . Eur J Clin Invest 1974;;4:163-174.
3 +
Brunzell JD, Hazzard WR, Porte D Jr, et al:  Evidence for a common, saturable, triglyceride removal mechanism for chylomicrons and very low density lipoproteins in man . J Clin Invest 1973;;52:1578-1585.
4 +
Beil U, Grundy SM, Crouse JR, et al:  Triglyceride and cholesterol metabolism in primary hypertriglyceridemia . Arteriosclerosis 1981;;2:44-57.
5 +
Grundy SM, Mok HYI, Zech L, et al:  Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia . J Clin Invest 1979;;63:1274-1283.
6 +
Zech LA, Grundy SM, Steinberg D, et al:  Kinetic model for production and metabolism of very low density lipoprotein triglycerides: Evidence for a slow production pathway and results from normolipidemic subjects . J Clin Invest 1979;;63:1262-1273.
7 +
Knittle JL, Ahrens EH Jr:  Carbohydrate metabolism in two forms of hypertriglyceridemia . J Clin Invest 1964;;43:485-495.
8 +
Brown MS, Goldstein JL, Fredrickson DA:  Familial type 3 hyperlipoproteinemia (dysbetalipoproteinemia) , in Stanbury JB, Wyngaarden JB, Fredrickson DS, et al (eds): The Metabolic Basis of Inherited Disease , ed 5. New York, McGraw-Hill Book Co Inc, 1983;, pp 665-671.
9 +
Grundy SM, Mok HYI:  Chylomicron clearance in normal and hyperlipidemic man . Metabolism 1976;;25:1227-1239.
10 +
Metropolitan Life Insurance Company Statistical Bulletin, 1983.
11 +
Brunzell JD, Porte D Jr, Bierman EL:  Reversible abnormalities in postheparin lipolytic activity during the late phase of release in diabetes mellitus (postheparin lipolytic activity in diabetes) . Metabolism 1975;;24:1123-1137.
12 +
Brunzell JD, Chait A, Nikkila EA, et al:  Heterogeneity of primary lipoprotein lipase deficiency . Metabolism 1980;;29:624-629.
13 +
Pykalisto OJ, Smith PH, Brunzell JD:  Determinants of human adipose tissue lipoprotein lipase: Effect of diabetes and obesity on basal- and diet-induced activity . J Clin Invest 1975;;56:1108-1117.
14 +
Brunzell JD, Porte D Jr,  Bierman EL: Abnormal lipoprotein-lipase-mediated plasma triglyceride removal in untreated diabetes mellitus associated and hypertriglyceridemia . Metabolism 1979;;28:902-907.
15 +
Krauss RM, Levy RI, Fredrickson DS:  Selective measurement of two lipase activities in postheparin plasma from normal subjects and patients with hyperlipoproteinemia . J Clin Invest 1974;;54:1107-1124.
16 +
Greenberg BH, Blackwelder WC, Levy RI:  Primary type V hyperlipoproteinemia: A descriptive study in 32 families . Ann Intern Med 1977;;87:526-534.
17 +
Fallat RW, Glueck CJ:  Familial and acquired type V hyperlipoproteinemia . Atherosclerosis 1976;;23:41-62.
18 +
Yeshurun D, Chung H, Gotto AM Jr, et al:  Primary type V hyperlipoproteinemia in childhood . JAMA 1977;;238:2518-2520.
19 +
Huttunen JK, Ehnholm C, Kekki M, et al:  Post-heparin plasma lipoprotein lipase and hepatic lipase in normal subjects and in patients with hypertriglyceridemia: Correlations to sex, age and various parameters of triglyceride metabolism . Clin Sci Mol Med 1976;;50:249-260.
20 +
Greten H, DeGrella R, Klose G, et al:  Measurement of two plasma triglyceride lipases by immunochemical method: Studies in patients with hypertriglyceridemia . J Lipid Res 1976;; 17:203-210.
21 +
Persson B:  Lipoprotein lipase activity of human adipose tissue in health and in some diseases with hyperlipidemia as a common feature . Acta Med Scand 1973;;193:457-462.
22 +
Kwiterowich PO, Farah JR, Brown WV, et al:  The clinical, biochemical, and familial presentation of type V hyperlipoproteinemia in childhood . Pediatrics 1977;;59:513-525.
23 +
Taskinen M-R, Nikkila EA:  High density lipoprotein subfractions in relation to lipoprotein lipase activity of tissues in man: Evidence for reciprocal regulation of HDL and HDL levels by lipoprotein lipase . Clin Chim Acta 1981;; 112:325-332.
24 +
Brown WV, Baginsky ML:  Inhibition of lipoprotein lipase by an apoprotein of human very low density lipoprotein . Biochem Biophys Res Commun 1972;;46:375-382.
25 +
Gregg RE, Ronan R, Zech LA, et al:  Abnormal metabolism of apolipoprotein E4 . Circulation 1982;;66( (suppl 2) ):160.
26 +
Abrams JJ, Ginsberg H, Grundy SM:  Metabolism of cholesterol and plasma triglycerides in nonketotic diabetes mellitus . Diabetes 1982;;31:903-910.
27 +
Bagdade JD, Porte D Jr, Bierman EL:  Acute insulin withdrawal and regulation of plasma triglyceride removal in diabetic subjects . Diabetes 1968;;17:127-132.
28 +
Pykalisto O, Goldberg A, Brunzell J:  Reversal of decreased human adipose tissue lipoprotein lipase and hypertriglyceridemia after treatment of hypothyroidism . J Clin Endocrinol Metabol 1976;;43:591-600.
29 +
Abrams JJ, Grundy SM:  Metabolism of plasma triglycerides in hypothyroidism and hyperthyroidism in man . J Lipid Res 1981;; 22:307-322.
30 +
Brunzell JD, Bierman EL:  Chylomicronemia syndrome: Interaction of genetic and acquired hypertriglyceridemia . Med Clin North Am 1982;;66:455-468.
31 +
Nikkila EA:  Familial lipoprotein lipase deficiency and related disorders of chylomicron metabolism , in Stanbury JB, Wyngaarden JB, Fredrickson DS, et al (eds): The Metabolic Basis of Inherited Disease , ed 5. New York, McGraw-Hill Book Co Inc, 1983;, pp 665-671.
32 +
Greenberger NJ, Hatch FT, Drummey GD, et al:  Pancreatitis and hyperlipidemia: A study of serum lipid alterations in 25 patients with acute pancreatitis . Medicine 1966;;45:161-174.
33 +
Isselbacher KJ, Greenberger NJ:  Metabolic effects of alcohol on liver . N Engl J Med 1964;;270:351-356.
34 +
Mendelson JH, Mello NK:  Alcohol induced hyperlipidemia and beta lipoproteins . Science 1973;;180:1372-1374.
35 +
Levy RI, Fredrickson DS:  The current status of hypolipidemic drugs . Postgrad Med 1970;;47:130-136.
36 +
Grundy SM, Ahrens EH Jr, Salen G, et al:  Mechanisms of action of clofibrate on cholesterol metabolism in patients with hyperlipidemia . J Lipid Res 1972;;13:531-551.
37 +
Boberg J, Boberg M, Gross R, et al:  The effect of treatment with clofibrate on hepatic triglyceride and lipoprotein lipase activities of post heparin plasma in male patients with hyperlipidemia . Atherosclerosis 1977;;27:499-503.
38 +
Lithell H, Boberg J, Hellsing K, et al:  Increase of the lipoprotein-lipase activity in human skeletal muscle during clofibrate administration . Eur J Clin Invest 1978;;8:67-74.
39 +
Taylor KG, Holdsworth G, Dalton DJ:  Clofibrate increases lipoprotein-lipase activity in adipose tissue of hypertriglyceridemia patients . Lancet 1977;;2:1106-1107.
40 +
Nikkila EA, Huttunen JK, Ehnholm C:  Effect of clofibrate on postheparin plasma triglyceride lipase activities in patients with hypertriglyceridemia . Metabolism 1977;;26:179-186.
41 +
Kesaniemi YA, Grundy SM:  Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglycerides in man . JAMA 1984;;17:2241-2246.
42 +
Grundy SM, Mok HYI, Zech L, et al:  Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man . J Lipid Res 1981;;22:24-36.
43 +
Carlson LA, Wahlberg G:  Relative increase in apolipoprotein CII content of VLDL and chylomicrons in a case with massive type 5 hyperlipoproteinemia by nicotinic acid . Atherosclerosis 1978;;31:77-84.
44 +
Creger PL, Moersch GW, Neuklis WA:  Structure/activity relationship of gemfibrozil (CI-719) and related compounds . Proc R Soc Med 1976;;69( (suppl 2) ):3-5.
45 +
Nash DT: Gemfibrozil:  A new lipid lowering agent . J Med 1980;;11:107-116.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Fredrickson DS, Lees RS:  A system for phenotyping hyperlipoproteinemia . Circulation 1965;;31:321-327.
2 +
Kissebah AH, Adams PW, Harrigan P, et al:  The mechanism of action of clofibrate and tetranicotinolyfructose (Bradilan) on the kinetics of plasma free fatty acid and triglyceride transport in type IV and type V hypertriglyceridaemia . Eur J Clin Invest 1974;;4:163-174.
3 +
Brunzell JD, Hazzard WR, Porte D Jr, et al:  Evidence for a common, saturable, triglyceride removal mechanism for chylomicrons and very low density lipoproteins in man . J Clin Invest 1973;;52:1578-1585.
4 +
Beil U, Grundy SM, Crouse JR, et al:  Triglyceride and cholesterol metabolism in primary hypertriglyceridemia . Arteriosclerosis 1981;;2:44-57.
5 +
Grundy SM, Mok HYI, Zech L, et al:  Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia . J Clin Invest 1979;;63:1274-1283.
6 +
Zech LA, Grundy SM, Steinberg D, et al:  Kinetic model for production and metabolism of very low density lipoprotein triglycerides: Evidence for a slow production pathway and results from normolipidemic subjects . J Clin Invest 1979;;63:1262-1273.
7 +
Knittle JL, Ahrens EH Jr:  Carbohydrate metabolism in two forms of hypertriglyceridemia . J Clin Invest 1964;;43:485-495.
8 +
Brown MS, Goldstein JL, Fredrickson DA:  Familial type 3 hyperlipoproteinemia (dysbetalipoproteinemia) , in Stanbury JB, Wyngaarden JB, Fredrickson DS, et al (eds): The Metabolic Basis of Inherited Disease , ed 5. New York, McGraw-Hill Book Co Inc, 1983;, pp 665-671.
9 +
Grundy SM, Mok HYI:  Chylomicron clearance in normal and hyperlipidemic man . Metabolism 1976;;25:1227-1239.
10 +
Metropolitan Life Insurance Company Statistical Bulletin, 1983.
11 +
Brunzell JD, Porte D Jr, Bierman EL:  Reversible abnormalities in postheparin lipolytic activity during the late phase of release in diabetes mellitus (postheparin lipolytic activity in diabetes) . Metabolism 1975;;24:1123-1137.
12 +
Brunzell JD, Chait A, Nikkila EA, et al:  Heterogeneity of primary lipoprotein lipase deficiency . Metabolism 1980;;29:624-629.
13 +
Pykalisto OJ, Smith PH, Brunzell JD:  Determinants of human adipose tissue lipoprotein lipase: Effect of diabetes and obesity on basal- and diet-induced activity . J Clin Invest 1975;;56:1108-1117.
14 +
Brunzell JD, Porte D Jr,  Bierman EL: Abnormal lipoprotein-lipase-mediated plasma triglyceride removal in untreated diabetes mellitus associated and hypertriglyceridemia . Metabolism 1979;;28:902-907.
15 +
Krauss RM, Levy RI, Fredrickson DS:  Selective measurement of two lipase activities in postheparin plasma from normal subjects and patients with hyperlipoproteinemia . J Clin Invest 1974;;54:1107-1124.
16 +
Greenberg BH, Blackwelder WC, Levy RI:  Primary type V hyperlipoproteinemia: A descriptive study in 32 families . Ann Intern Med 1977;;87:526-534.
17 +
Fallat RW, Glueck CJ:  Familial and acquired type V hyperlipoproteinemia . Atherosclerosis 1976;;23:41-62.
18 +
Yeshurun D, Chung H, Gotto AM Jr, et al:  Primary type V hyperlipoproteinemia in childhood . JAMA 1977;;238:2518-2520.
19 +
Huttunen JK, Ehnholm C, Kekki M, et al:  Post-heparin plasma lipoprotein lipase and hepatic lipase in normal subjects and in patients with hypertriglyceridemia: Correlations to sex, age and various parameters of triglyceride metabolism . Clin Sci Mol Med 1976;;50:249-260.
20 +
Greten H, DeGrella R, Klose G, et al:  Measurement of two plasma triglyceride lipases by immunochemical method: Studies in patients with hypertriglyceridemia . J Lipid Res 1976;; 17:203-210.
21 +
Persson B:  Lipoprotein lipase activity of human adipose tissue in health and in some diseases with hyperlipidemia as a common feature . Acta Med Scand 1973;;193:457-462.
22 +
Kwiterowich PO, Farah JR, Brown WV, et al:  The clinical, biochemical, and familial presentation of type V hyperlipoproteinemia in childhood . Pediatrics 1977;;59:513-525.
23 +
Taskinen M-R, Nikkila EA:  High density lipoprotein subfractions in relation to lipoprotein lipase activity of tissues in man: Evidence for reciprocal regulation of HDL and HDL levels by lipoprotein lipase . Clin Chim Acta 1981;; 112:325-332.
24 +
Brown WV, Baginsky ML:  Inhibition of lipoprotein lipase by an apoprotein of human very low density lipoprotein . Biochem Biophys Res Commun 1972;;46:375-382.
25 +
Gregg RE, Ronan R, Zech LA, et al:  Abnormal metabolism of apolipoprotein E4 . Circulation 1982;;66( (suppl 2) ):160.
26 +
Abrams JJ, Ginsberg H, Grundy SM:  Metabolism of cholesterol and plasma triglycerides in nonketotic diabetes mellitus . Diabetes 1982;;31:903-910.
27 +
Bagdade JD, Porte D Jr, Bierman EL:  Acute insulin withdrawal and regulation of plasma triglyceride removal in diabetic subjects . Diabetes 1968;;17:127-132.
28 +
Pykalisto O, Goldberg A, Brunzell J:  Reversal of decreased human adipose tissue lipoprotein lipase and hypertriglyceridemia after treatment of hypothyroidism . J Clin Endocrinol Metabol 1976;;43:591-600.
29 +
Abrams JJ, Grundy SM:  Metabolism of plasma triglycerides in hypothyroidism and hyperthyroidism in man . J Lipid Res 1981;; 22:307-322.
30 +
Brunzell JD, Bierman EL:  Chylomicronemia syndrome: Interaction of genetic and acquired hypertriglyceridemia . Med Clin North Am 1982;;66:455-468.
31 +
Nikkila EA:  Familial lipoprotein lipase deficiency and related disorders of chylomicron metabolism , in Stanbury JB, Wyngaarden JB, Fredrickson DS, et al (eds): The Metabolic Basis of Inherited Disease , ed 5. New York, McGraw-Hill Book Co Inc, 1983;, pp 665-671.
32 +
Greenberger NJ, Hatch FT, Drummey GD, et al:  Pancreatitis and hyperlipidemia: A study of serum lipid alterations in 25 patients with acute pancreatitis . Medicine 1966;;45:161-174.
33 +
Isselbacher KJ, Greenberger NJ:  Metabolic effects of alcohol on liver . N Engl J Med 1964;;270:351-356.
34 +
Mendelson JH, Mello NK:  Alcohol induced hyperlipidemia and beta lipoproteins . Science 1973;;180:1372-1374.
35 +
Levy RI, Fredrickson DS:  The current status of hypolipidemic drugs . Postgrad Med 1970;;47:130-136.
36 +
Grundy SM, Ahrens EH Jr, Salen G, et al:  Mechanisms of action of clofibrate on cholesterol metabolism in patients with hyperlipidemia . J Lipid Res 1972;;13:531-551.
37 +
Boberg J, Boberg M, Gross R, et al:  The effect of treatment with clofibrate on hepatic triglyceride and lipoprotein lipase activities of post heparin plasma in male patients with hyperlipidemia . Atherosclerosis 1977;;27:499-503.
38 +
Lithell H, Boberg J, Hellsing K, et al:  Increase of the lipoprotein-lipase activity in human skeletal muscle during clofibrate administration . Eur J Clin Invest 1978;;8:67-74.
39 +
Taylor KG, Holdsworth G, Dalton DJ:  Clofibrate increases lipoprotein-lipase activity in adipose tissue of hypertriglyceridemia patients . Lancet 1977;;2:1106-1107.
40 +
Nikkila EA, Huttunen JK, Ehnholm C:  Effect of clofibrate on postheparin plasma triglyceride lipase activities in patients with hypertriglyceridemia . Metabolism 1977;;26:179-186.
41 +
Kesaniemi YA, Grundy SM:  Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglycerides in man . JAMA 1984;;17:2241-2246.
42 +
Grundy SM, Mok HYI, Zech L, et al:  Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man . J Lipid Res 1981;;22:24-36.
43 +
Carlson LA, Wahlberg G:  Relative increase in apolipoprotein CII content of VLDL and chylomicrons in a case with massive type 5 hyperlipoproteinemia by nicotinic acid . Atherosclerosis 1978;;31:77-84.
44 +
Creger PL, Moersch GW, Neuklis WA:  Structure/activity relationship of gemfibrozil (CI-719) and related compounds . Proc R Soc Med 1976;;69( (suppl 2) ):3-5.
45 +
Nash DT: Gemfibrozil:  A new lipid lowering agent . J Med 1980;;11:107-116.

Letters

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Comment

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems