Triglyceride Uptake and Lipoprotein Lipase–Generated Fatty Acid Spillover in the Splanchnic Bed of Dogs
- Robert H. Nelson1,
- Dale S. Edgerton2,
- Rita Basu1,
- Justin C. Roesner1,
- Alan D. Cherrington2 and
- John M. Miles1
- 1Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota
- 2Department of Molecular Physiology and Biophysics, Vanderbilt School of Medicine, Nashville, Tennessee
- Address correspondence and reprint requests to John M. Miles, MD, Endocrine Research Unit, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. E-mail: miles.john{at}mayo.edu
Abstract
The action of lipoprotein lipase on triglyceride-rich lipoproteins generates fatty acids that are either transported into tissues or mix with circulating free fatty acids (FFAs) via a process known as spillover. In the present study, arterial, portal vein, and hepatic vein sampling catheters were surgically placed in nine mongrel dogs. The animals were subsequently studied after a 42-h fast during infusion of [14C]oleate and a lipid emulsion containing [3H]triolein; the emulsion was used as a surrogate for the study of chylomicron metabolism. More than one-half of splanchnic [3H]triglyceride uptake occurred in the liver, and substantial fractional spillover of [3H]oleate was observed in both liver and nonhepatic tissues (∼50% each). There was a significant correlation between FFA release from nonhepatic tissues (presumably visceral fat) and nonhepatic fractional spillover (R = 0.81, P < 0.01), consistent with a model in which the rate of intracellular lipolysis influences spillover by determining the direction of net fatty acid flow between the cell and the interstitium. There was a significant correlation between “true” and “net” splanchnic spillover (R = 0.84, P < 0.005), the latter representing calculation of spillover between arterial and hepatic venous blood without portal venous data. Metabolism of chylomicron triglycerides in visceral fat may be an important source of portal venous FFAs.
- FFA, free fatty acid
- HPLC, high-performance liquid chromatography
- HSL, hormone-sensitive lipase
- LPL, lipoprotein lipase
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 6 April 2007. DOI: 10.2337/db06-1657.
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Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1657.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted March 29, 2007.
- Received November 27, 2007.
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