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

• Published in: Journal of lipid research Vol. 47; no. 11; pp. 2562 - 2574
• Main Authors: Vedala, Aruna, Wang, Wei, Neese, Richard A., Christiansen, Mark P., Hellerstein, Marc K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2006; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Administration, Oral; Adult; Biological Transport; Case-Control Studies; diabetes; Diet; Fatty Acids, Nonesterified - blood; Female; Gas Chromatography-Mass Spectrometry; hepatic cytosolic pool; Humans; hypertriglyceridemia; Kinetics; Lipogenesis; Lipoproteins, VLDL - metabolism; Male; mass spectrometry; Middle Aged; nonesterified fatty acid; obesity; stable isotopes; Time Factors; Triglycerides - metabolism; very low density lipoprotein; stable isotopes; hepatic cytosolic pool; hypertriglyceridemia; nonesterified fatty acid; mass spectrometry; very low density lipoprotein; diabetes; obesity
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M600200-JLR200

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.