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

Robert H. Nelson, Rita Basu, C. Michael Johnson, Robert A. Rizza, John M. Miles

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 ( 14C or 13C) oleate and 3H triolein, the latter incorporated into a lipid emulsion as a surrogate for chylomicrons. Spillover was determined by measuring production of 3H 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.

Original languageEnglish (US)
Pages (from-to)2878-2884
Number of pages7
JournalDiabetes
Volume56
Issue number12
DOIs
StatePublished - Dec 2007

Fingerprint

Viscera
Lipase
Fatty Acids
Triglycerides
Chylomicrons
Oleic Acid
Lipoproteins
Triolein
Portal Vein
Emulsions
Nonesterified Fatty Acids
Hydrolysis
Research Design
Theoretical Models
Carbon
Lipids
Liver

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Nelson, R. H., Basu, R., Johnson, C. M., Rizza, R. A., & Miles, J. M. (2007). Splanchnic spillover of extracellular lipase-generated fatty acids in overweight and obese humans. Diabetes, 56(12), 2878-2884. https://doi.org/10.2337/db07-0812

Splanchnic spillover of extracellular lipase-generated fatty acids in overweight and obese humans. / Nelson, Robert H.; Basu, Rita; Johnson, C. Michael; Rizza, Robert A.; Miles, John M.

In: Diabetes, Vol. 56, No. 12, 12.2007, p. 2878-2884.

Research output: Contribution to journalArticle

Nelson, RH, Basu, R, Johnson, CM, Rizza, RA & Miles, JM 2007, 'Splanchnic spillover of extracellular lipase-generated fatty acids in overweight and obese humans', Diabetes, vol. 56, no. 12, pp. 2878-2884. https://doi.org/10.2337/db07-0812
Nelson, Robert H. ; Basu, Rita ; Johnson, C. Michael ; Rizza, Robert A. ; Miles, John M. / Splanchnic spillover of extracellular lipase-generated fatty acids in overweight and obese humans. In: Diabetes. 2007 ; Vol. 56, No. 12. pp. 2878-2884.
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AB - 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 ( 14C or 13C) oleate and 3H triolein, the latter incorporated into a lipid emulsion as a surrogate for chylomicrons. Spillover was determined by measuring production of 3H 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.

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