Delayed secretory pathway contributions to VLDL-triglycerides from plasma NEFA, diet, and de novo lipogenesis in humans.
Level 3 - non-randomized controlled study
Non-randomized comparative metabolic study
PubMed 16929033 · doi:10.1194/jlr.M600200-JLR200
What was done
Stable isotope tracer kinetics were used to quantify the contributions of plasma non-esterified fatty acids (NEFA), dietary fatty acids, and de novo lipogenesis (DNL) to VLDL-triglycerides (TG) via immediate versus delayed secretory pathways. The study evaluated 17 participants across three groups: 5 lean normolipidemic controls, 6 obese hypertriglyceridemic (HPTG) non-diabetics, and 6 obese HPTG diabetics. Subjects received intravenous [2H31]palmitate and [1-13C1]acetate and oral [2H35]stearate for 30 hours before an overnight fast, followed by a continuous infusion of [1,2,3,4-13C4]palmitate during a subsequent 12-hour fast.
What was found
Contributions of plasma NEFA via the immediate pathway were 64 ± 15% in controls, 33 ± 6% in HPTG non-diabetics, and 58 ± 2% in diabetic HPTG subjects. Fractional contributions from the delayed storage pool were: - Dietary fatty acids: 2.0 ± 0.9% (controls), 2.5 ± 1% (HPTG non-diabetics), and 12 ± 2% (diabetic HPTG). - De novo lipogenesis: 3 ± 0.3% (controls), 14 ± 3% (HPTG non-diabetics), and 13 ± 4% (diabetic HPTG). - Delayed NEFA: 15 ± 4% (controls), 20 ± 4% (HPTG non-diabetics), and 30 ± 3% (diabetic HPTG). Overall VLDL-TG production rates and absolute input rates from the delayed pool were significantly higher in both HPTG groups than in controls.
Why it matters
The findings provide direct kinetic confirmation of an intrahepatic TG storage pool in humans, demonstrating that delayed secretory pathway turnover and substrate origins differ between diabetic and non-diabetic hypertriglyceridemia.
Limits
The sample size is very small (n = 5–6 per group). The study is cross-sectional and observational, preventing causal determination between specific metabolic pathways and clinical phenotypes. The abstract does not report baseline patient characteristics such as age, sex distribution, glycemic control levels, or exact statistical significance values (p-values) for the between-group differences.
Cited by
- contradicts Palmitate is the primary saturated fatty acid produced by the liver via de novo lipogenesis.