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Sex differences in multiple steps in hepatic transport of palmitate support a balanced uptake mechanism

Sex differences in multiple steps in hepatic transport of palmitate support a balanced uptake... Abstract Hepatic clearance of long-chain fatty acids is substantially faster in females than in males, a fact that may underlie known gender-related differences in lipoprotein metabolism and associated disease states. To further investigate the transport steps responsible for this difference, we used a novel method combining multiple-indicator dilution and steady-state measurements of palmitate extraction from albumin solutions. We found that cytoplasmic transport of palmitate is sufficiently slow (diffusion constants 9.0 and 5.9 × 10 −9 cm 2 /s for male and female liver, respectively) that the steady-state concentration of palmitate in the center of the cell should be ∼0.5 of that found in the cytoplasm just beneath the plasma membrane. Previous studies in cultured liver cells using nonphysiological fatty acids have shown more rapid cytoplasmic transport in females. This sex difference reflects higher concentrations of cytosolic fatty acid-binding protein, which acts as a carrier system to transport fatty acids across cell water layers. The current study confirmed slow cytoplasmic diffusion rates in intact perfused rat liver using a physiological fatty acid and found a similar female-to-male ratio. Female liver also had a greater influx rate constant and a larger vascular volume than male liver but had a similar rate of metabolism. Rapid cytoplasmic diffusion enhances movement of palmitate into deeper layers of the cell cytoplasm, thus reducing efflux. The larger sinusoidal volume in females not only permits more dissociation of palmitate from albumin within the sinusoids but also may generate a greater permeability-surface area product. These multiple sex-related differences combine to produce a nearly twofold greater steady-state uptake rate by female liver. cytoplasmic transport diffusion gradients fatty acid-binding proteins long-chain fatty acids sex factors carrier proteins membrane transport multiple-indicator dilution hepatic uptake rate constants mathematical models kinetics Footnotes Address for reprint requests: R. A. Weisiger, Div. of Gastroenterology and the Liver Center, Univ. of California, San Francisco, San Francisco, CA 94110-0538. This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-32898 (to R. A. Weisiger), DK-46922 (to B. A. Luxon), and Liver Core Center Grant DK-26743. B. A. Luxon is a recipient of the Mary Richards Liver Scholar Award from the American Liver Foundation. Copyright © 1998 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

Sex differences in multiple steps in hepatic transport of palmitate support a balanced uptake mechanism

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
Publisher site
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Abstract

Abstract Hepatic clearance of long-chain fatty acids is substantially faster in females than in males, a fact that may underlie known gender-related differences in lipoprotein metabolism and associated disease states. To further investigate the transport steps responsible for this difference, we used a novel method combining multiple-indicator dilution and steady-state measurements of palmitate extraction from albumin solutions. We found that cytoplasmic transport of palmitate is sufficiently slow (diffusion constants 9.0 and 5.9 × 10 −9 cm 2 /s for male and female liver, respectively) that the steady-state concentration of palmitate in the center of the cell should be ∼0.5 of that found in the cytoplasm just beneath the plasma membrane. Previous studies in cultured liver cells using nonphysiological fatty acids have shown more rapid cytoplasmic transport in females. This sex difference reflects higher concentrations of cytosolic fatty acid-binding protein, which acts as a carrier system to transport fatty acids across cell water layers. The current study confirmed slow cytoplasmic diffusion rates in intact perfused rat liver using a physiological fatty acid and found a similar female-to-male ratio. Female liver also had a greater influx rate constant and a larger vascular volume than male liver but had a similar rate of metabolism. Rapid cytoplasmic diffusion enhances movement of palmitate into deeper layers of the cell cytoplasm, thus reducing efflux. The larger sinusoidal volume in females not only permits more dissociation of palmitate from albumin within the sinusoids but also may generate a greater permeability-surface area product. These multiple sex-related differences combine to produce a nearly twofold greater steady-state uptake rate by female liver. cytoplasmic transport diffusion gradients fatty acid-binding proteins long-chain fatty acids sex factors carrier proteins membrane transport multiple-indicator dilution hepatic uptake rate constants mathematical models kinetics Footnotes Address for reprint requests: R. A. Weisiger, Div. of Gastroenterology and the Liver Center, Univ. of California, San Francisco, San Francisco, CA 94110-0538. This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-32898 (to R. A. Weisiger), DK-46922 (to B. A. Luxon), and Liver Core Center Grant DK-26743. B. A. Luxon is a recipient of the Mary Richards Liver Scholar Award from the American Liver Foundation. Copyright © 1998 the American Physiological Society

Journal

AJP - Gastrointestinal and Liver PhysiologyThe American Physiological Society

Published: Jan 1, 1998

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