HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meijssen, S. Articles by Erkelens, D. W. Search for Related Content PubMed PubMed Citation Articles by Meijssen, S. Articles by Erkelens, D. W. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 1096-1102, July 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

In vivo evidence of defective postprandial and postabsorptive free fatty acid metabolism in familial combined hyperlipidemia

Correspondence to: M. Castro Cabezas

Overproduction of very low density lipoprotein (VLDL) is the major characteristic of subjects with familial combined hyperlipidemia (FCHL). As enhanced free fatty acid (FFA) flux to the liver may be one of the determinants of VLDL overproduction, we studied FFA changes and products of hepatic FFA metabolism in response to a 24-h oral fat loading test (50 g/m²) in 7 FCHL subjects and 7 matched control subjects. The response to the meal was subdivided into a postprandial (up to 8 h after ingestion of the meal) and postabsorptive period (from 8 to 24 h). Although postheparin plasma lipolytic activities were not different between both groups, the postprandial FFA area under the curve (FFA-AUC) and FFA incremental area under the curve (FFA-dAUC) were higher in FCHL subjects than in control subjects (6.05 ± 0.45 vs. 3.43 ± 0.46 and 2.60 ± 0.49 vs. 0.96 ± 0.31 mmol · h/L, respectively; P < 0.01 for each). The postprandial increase in ketone bodies was almost four times higher in FCHL patients. As ketogenesis occurs predominantly in hepatocytes, these findings suggest that during the postprandial period in FCHL an increased flux of FFA to the liver occurs, possibly because of inadequate incorporation of FFA into triglycerides (TGs) in adipocytes. In the postabsorptive period, FFA and ketone bodies significantly decreased in FCHL subjects, in contrast to control subjects, in whom both increased. These results may represent a diminished release of FFA from adipocytes by hormone-sensitive lipase (HSL) in FCHL patients. The decrease in postabsorptive FFA and ketone bodies in FCHL patients could not be explained by insulin-mediated inhibition of HSL, as both FCHL subjects and control subjects had similar postabsorptive insulin concentrations, which were below fasting concentrations.

This study provides in vivo evidence of impaired metabolism of postprandial FFA in FCHL, which may explain in part the hepatic VLDL overproduction characteristic of FCHL subjects.—Meijssen, S., M. Castro Cabezas, T. B. Twickler, H. Jansen, and D. W. Erkelens. In vivo evidence of defective postprandial and postabsorptive free fatty acid metabolism in familial combined hyperlipidemia. J. Lipid Res. 2000. 41: 1096;–1102.

Supplementary key words: atherosclerosis, apoB overproduction, VLDL, triglycerides, ketone bodies, postprandial lipemia, acylation-stimulating protein, hormone-sensitive lipase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. P. H. van Wijk, M. C. Cabezas, E. J. P. de Koning, T. J. Rabelink, R. van der Geest, and I. M. Hoepelman In Vivo Evidence of Impaired Peripheral Fatty Acid Trapping in Patients with Human Immunodeficiency Virus-Associated Lipodystrophy J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3575 - 3582. [Abstract] [Full Text] [PDF]

				M. Castro Cabezas, C. Verseyden, S. Meijssen, H. Jansen, and D. W. Erkelens Effects of Atorvastatin on the Clearance of Triglyceride-Rich Lipoproteins in Familial Combined Hyperlipidemia J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 5972 - 5980. [Abstract] [Full Text] [PDF]

				C.C. Shoulders, E.L. Jones, and R.P. Naoumova Genetics of familial combined hyperlipidemia and risk of coronary heart disease Hum. Mol. Genet., April 1, 2004; 13(90001): R149 - 160. [Abstract] [Full Text] [PDF]

				A. J van Oostrom, H. van Dijk, C. Verseyden, A. D Sniderman, K. Cianflone, T. J Rabelink, and M. Castro Cabezas Addition of glucose to an oral fat load reduces postprandial free fatty acids and prevents the postprandial increase in complement component 3 Am. J. Clinical Nutrition, March 1, 2004; 79(3): 510 - 515. [Abstract] [Full Text] [PDF]

				C. Verseyden, S. Meijssen, H. van Dijk, H. Jansen, and M. C. Cabezas Effects of atorvastatin on fasting and postprandial complement component 3 response in familial combined hyperlipidemia J. Lipid Res., November 1, 2003; 44(11): 2100 - 2108. [Abstract] [Full Text] [PDF]

				C.J.M. Halkes, H. van Dijk, C. Verseyden, P.P.Th. de Jaegere, H.W.M Plokker, S. Meijssen, D.W. Erkelens, and M. C. Cabezas Gender Differences in Postprandial Ketone Bodies in Normolipidemic Subjects and in Untreated Patients With Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1875 - 1880. [Abstract] [Full Text] [PDF]

				M. Guerin, P. Egger, C. Soudant, W. Le Goff, A. van Tol, R. Dupuis, and M. J. Chapman Cholesteryl ester flux from HDL to VLDL-1 is preferentially enhanced in type IIB hyperlipidemia in the postprandial state J. Lipid Res., October 1, 2002; 43(10): 1652 - 1660. [Abstract] [Full Text] [PDF]

				P. M. H. Eurlings, C. J. H. van der Kallen, J. M. W. Geurts, P. Kouwenberg, W. D. Boeckx, and T. W. A. de Bruin Identification of differentially expressed genes in subcutaneous adipose tissue from subjects with familial combined hyperlipidemia J. Lipid Res., June 1, 2002; 43(6): 930 - 935. [Abstract] [Full Text] [PDF]

				S. Meijssen, H. van Dijk, C. Verseyden, D.W. Erkelens, and M. C. Cabezas Delayed and Exaggerated Postprandial Complement Component 3 Response in Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., May 1, 2002; 22(5): 811 - 816. [Abstract] [Full Text] [PDF]

				S. Meijssen, R. J. Derksen, S. Bilecen, D. W. Erkelens, and M. C. Cabezas In Vivo Modulation of Plasma Free Fatty Acids in Patients with Familial Combined Hyperlipidemia Using Lipid-Lowering Medication J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1576 - 1580. [Abstract] [Full Text] [PDF]

				C. Verseyden, S. Meijssen, and M. C. Cabezas Postprandial changes of apoB-100 and apoB-48 in TG rich lipoproteins in familial combined hyperlipidemia J. Lipid Res., February 1, 2002; 43(2): 274 - 280. [Abstract] [Full Text] [PDF]

				C.J.M. Halkes, H. van Dijk, P.P.T. de Jaegere, H.W.M. Plokker, Y. van der Helm, D. W. Erkelens, and M. Castro Cabezas Postprandial Increase of Complement Component 3 in Normolipidemic Patients With Coronary Artery Disease: Effects of Expanded-Dose Simvastatin Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1526 - 1530. [Abstract] [Full Text] [PDF]

				M. P. Stojiljkovic, D. Zhang, H. F. Lopes, C. G. Lee, T. L. Goodfriend, and B. M. Egan Hemodynamic effects of lipids in humans Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1674 - R1679. [Abstract] [Full Text] [PDF]

				T. G. Redgrave, G. F. Watts, I. J. Martins, P. H. R. Barrett, J. C. L. Mamo, S. B. Dimmitt, and A. D. Marais Chylomicron remnant metabolism in familial dyslipidemias studied with a remnant-like emulsion breath test J. Lipid Res., May 1, 2001; 42(5): 710 - 715. [Abstract] [Full Text]