Sex differences in hepatic uptake of long chain fatty acids in single-pass perfused rat liver

Abstract

The primary determinants of hepatic uptake of long chain fatty acids have been considered to be the plasma concentrations of fatty acid and albumin, with little or no intrinsic control by the hepatocyte itself. However, recent studies of liver cell suspensions have shown that in immature, adult, castrated, and hormone-treated rats, sex steroids exert striking effects on [(14)C]oleate uptake and utilization (which were significantly increased by estradiol and diminished by testosterone). To determine whether these observed sex differences in fatty acid uptake also were present in the intact liver, single-pass [(14)C]oleate uptake was measured in isolated perfused livers. Livers from sexually mature female and male rats were perfused single-pass with albumin-bound [(14)C]oleate in Krebs-Ringer bicarbonate buffer. Net uptake, calculated as the product of the transhepatic difference in (14)C-labeled fatty acid concentration and perfusate flow rate, reached a steady-state within 1 min and remained constant throughout the 10-min perfusion period. At 0.17 mM [(14)C]oleate and 0.15 mM albumin, extraction fraction and net uptake of [(14)C]oleate per gram liver were more than twice as great in females as in male livers (0.33 +/- 0.03 versus 0.15 +/- 0.02, P < 0.001; and 218 +/- 22 versus 101 +/- 15 nmol/g liver, P < 0.01, with parallel differences in [(14)C]oleate total utilization and incorporation into triglycerides. Significant differences in uptake also were observed at higher [(14)C]oleate concentrations (0.34 and 0.68 mM). Under all conditions, oxidation of [(14)C]oleate in female liver equaled or exceeded that in male liver, indicating that the increased incorporation into triglycerides and other glycerolipids was not simply the result of differences in the distribution of [(14)C]oleate among cellular metabolic pathways. These studies demonstrate that in the intact liver, as in isolated hepatocytes, there are profound sex differences in the uptake of long chain fatty acids. This difference may account in part for the observed sex steroid effects on hepatic triglyceride biosynthesis and VLDL production. The mechanism of these uptake differences remains to be determined.-Kushlan, M. C., J. L. Gollan, W-L. Ma, and R. K. Ockner. Sex differences in hepatic uptake of long chain fatty acids in single-pass perfused rat liver.