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) All Versions of this Article: M600200-JLR200v1 47/11/2562    most recent 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 Vedala, A. Articles by Hellerstein, M. K. Search for Related Content PubMed PubMed Citation Articles by Vedala, A. Articles by Hellerstein, M. K. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 2562-2574, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

Delayed secretory pathway contributions to VLDL-triglycerides from plasma NEFA, diet, and de novo lipogenesis in humans

Aruna Vedala^*, Wei Wang^*, Richard A. Neese^*, Mark P. Christiansen^* and Marc K. Hellerstein^1,*,

^* Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA 94720
Division of Endocrinology and Metabolism, San Francisco General Hospital, University of California, San Francisco, CA 94110

Published, JLR Papers in Press, August 23, 2006.

¹ To whom correspondence should be addressed. e-mail: march{at}nature.berkeley.edu

ABSTRACT

Newly synthesized triglyceride (TG) may exit the liver immediately as VLDL-TG or be stored and secreted after a delay. We quantified the contributions from plasma NEFA, diet, and de novo lipogenesis (DNL) to VLDL-TG via immediate and delayed pathways in five lean, normolipidemic subjects; six obese, hypertriglyceridemic (HPTG) nondiabetics; and six obese, HPTG diabetics. Intravenous [²H₃₁]palmitate and [1-¹³C₁] acetate and oral [²H₃₅]stearate were administered for 30 h preceding an overnight fast. [1,2,3,4-¹³C₄]palmitate was infused during the subsequent 12 h fast. Contributions from plasma NEFA via the immediate pathway were 64 ± 15, 33 ± 6, and 58 ± 2% in control, HPTG, and diabetic HPTG, respectively. Delayed pool fractional contributions were as follows: dietary FA, 2.0 ± 0.9, 2.5 ± 1, and 12 ± 2%; DNL, 3 ± 0.3, 14 ± 3, and 13 ± 4%; delayed NEFA, 15 ± 4, 20 ± 4, and 30 ± 3%. VLDL-TG production rates and absolute input rates from the delayed pool were significantly higher in HPTG and diabetic HPTG than in controls. In conclusion, we provide direct kinetic evidence for a hepatic TG storage pool in humans and document its metabolic sources. The turnover time and sources of this pool differ in diabetic HPTG and nondiabetic HPTG, with potential therapeutic implications.

Supplementary key words hypertriglyceridemia • diabetes • obesity • hepatic cytosolic pool • stable isotopes • mass spectrometry • very low density lipoprotein • nonesterified fatty acid

Abbreviations: DNL, de novo lipogenesis; FAME, fatty acid methyl ester; GCRC, General Clinical Research Center; HPTG, hypertriglyceridemia, hypertriglyceridemic; MPE, molar percent excess; TG, triglyceride; TRL, triglyceride-rich lipoprotein

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

This article has been cited by other articles:

				S. Y. Bu, M. T. Mashek, and D. G. Mashek Suppression of Long Chain Acyl-CoA Synthetase 3 Decreases Hepatic de Novo Fatty Acid Synthesis through Decreased Transcriptional Activity J. Biol. Chem., October 30, 2009; 284(44): 30474 - 30483. [Abstract] [Full Text] [PDF]

				C. Beysen, E. J. Murphy, H. Nagaraja, M. Decaris, T. Riiff, A. Fong, M. K. Hellerstein, and P. J. Boyle A pilot study of the effects of pioglitazone and rosiglitazone on de novo lipogenesis in type 2 diabetes J. Lipid Res., December 1, 2008; 49(12): 2657 - 2663. [Abstract] [Full Text] [PDF]

				M. Adiels, S.-O. Olofsson, M.-R. Taskinen, and J. Boren Overproduction of Very Low-Density Lipoproteins Is the Hallmark of the Dyslipidemia in the Metabolic Syndrome Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1225 - 1236. [Abstract] [Full Text] [PDF]

				E. J. Parks, L. E. Skokan, M. T. Timlin, and C. S. Dingfelder Dietary Sugars Stimulate Fatty Acid Synthesis in Adults J. Nutr., June 1, 2008; 138(6): 1039 - 1046. [Abstract] [Full Text] [PDF]

				M. F-F Chong, L. Hodson, A. S Bickerton, R. Roberts, M. Neville, F. Karpe, K. N Frayn, and B. A Fielding Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding Am. J. Clinical Nutrition, April 1, 2008; 87(4): 817 - 823. [Abstract] [Full Text] [PDF]

				M. K. Hellerstein Exploiting Complexity and the Robustness of Network Architecture for Drug Discovery J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 1 - 9. [Abstract] [Full Text] [PDF]

				D. P.Y. Koonen, R. L. Jacobs, M. Febbraio, M. E. Young, C.-L. M. Soltys, H. Ong, D. E. Vance, and J. R.B. Dyck Increased Hepatic CD36 Expression Contributes to Dyslipidemia Associated With Diet-Induced Obesity Diabetes, December 1, 2007; 56(12): 2863 - 2871. [Abstract] [Full Text] [PDF]

				L. Hodson, A. S.T. Bickerton, S. E. McQuaid, R. Roberts, F. Karpe, K. N. Frayn, and B. A. Fielding The Contribution of Splanchnic Fat to VLDL Triglyceride Is Greater in Insulin-Resistant Than Insulin-Sensitive Men and Women: Studies in the Postprandial State Diabetes, October 1, 2007; 56(10): 2433 - 2441. [Abstract] [Full Text] [PDF]