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 [(2)H(31)]palmitate and [1-(13)C(1)] acetate and oral [(2)H(35)]stearate were administered for 30 h preceding an overnight fast. [1,2,3,4-(13)C(4)]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.
Highlights
Synthesized triglyceride (TG) may exit the liver immediately as VLDL-TG or be stored and secreted after a delay
Plasma NEFAs are considered to be the major source of VLDL-TG [12,13,14], dietary FAs carried in chylomicrons and FAs synthesized by hepatic de novo lipogenesis (DNL) can affect VLDL-TG metabolism in a number of ways
TG and VLDL cholesterol concentrations were significantly higher in the HPTG and diabetic HPTG groups compared with the control group
Summary
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. Delayed secretory pathway contributions to VLDL-triglycerides from plasma NEFA, diet, and de novo lipogenesis in humans. FAs released from lipolysis of chylomicrons may escape uptake by peripheral tissues and enter the plasma NEFA pool [15,16,17,18,19] This increased substrate supply may stimulate hepatic TG production. The hepatic cytosolic TG storage pool may contribute to VLDLTG released during the fasted state, via a delayed secretory pathway (Fig. 1)
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