Splanchnic spillover of extracellular lipase-generated fatty acids in overweight and obese humans

Diabetes. 2007 Dec;56(12):2878-84. doi: 10.2337/db07-0812. Epub 2007 Sep 19.

Abstract

Objective: Triglyceride-rich lipoproteins, primarily chylomicrons, can contribute to plasma free fatty acid (FFA) concentrations via spillover of fatty acids during intravascular hydrolysis into the venous effluent of some tissues. The present study was undertaken to determine whether spillover occurs in the splanchnic bed of humans.

Research design and methods: Arterial and hepatic venous blood was sampled in postabsorptive (n = 6; study A) and postprandial (n = 5; study B) obese humans during infusion of carbon-labeled ((14)C or (13)C) oleate and (3)H triolein, the latter incorporated into a lipid emulsion as a surrogate for chylomicrons. Spillover was determined by measuring production of (3)H oleate.

Results: Splanchnic spillover was higher than nonsplanchnic systemic spillover in both study A (60 +/- 7 vs. 24 +/- 6%; P < 0.01) and study B (54 +/- 3 vs. 16 +/- 5%; P < 0.005). Because portal vein sampling is not feasible in humans, assumptions regarding actual spillover in nonhepatic splanchnic tissues were required for the spillover calculation. A mathematical model was developed and demonstrated that nonhepatic splanchnic spillover rates in study A and study B of 69 and 80%, respectively, provided the best fit with the data. There was preferential splanchnic uptake of triglyceride fatty acids compared with FFAs in study B (fractional extraction 61 +/- 3 vs. 33 +/- 2%; P < 0.005).

Conclusions: These data confirm previous studies indicating that the transport of FFAs and triglyceride fatty acids are partitioned in tissues and indicate that splanchnic spillover from triglyceride-rich lipoproteins may be a significant source of both portal venous and systemic FFAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Fatty Acids, Nonesterified / blood*
  • Female
  • Hepatic Artery
  • Hepatic Veins
  • Humans
  • Hydrocortisone / blood
  • Lipase / metabolism*
  • Lipids / blood
  • Male
  • Middle Aged
  • Obesity / blood*
  • Overweight / blood*
  • Postprandial Period
  • Splanchnic Circulation / physiology*
  • Triglycerides / blood*

Substances

  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fatty Acids, Nonesterified
  • Lipids
  • Triglycerides
  • Cholesterol
  • Lipase
  • Hydrocortisone