Kushlan M C, Gollan J L, Ma W L, Ockner R K
J Lipid Res. 1981 Mar;22(3):431-6.
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.
长链脂肪酸肝脏摄取的主要决定因素一直被认为是脂肪酸和白蛋白的血浆浓度，肝细胞自身几乎没有内在调控作用。然而，最近对肝细胞悬液的研究表明，在未成熟、成年、去势及激素处理的大鼠中，性类固醇对[¹⁴C]油酸的摄取和利用有显著影响（雌二醇使其显著增加，睾酮使其减少）。为确定在完整肝脏中是否也存在这些观察到的脂肪酸摄取性别差异，在离体灌注肝脏中测量了单次通过的[¹⁴C]油酸摄取。将性成熟雌性和雄性大鼠的肝脏在Krebs - Ringer碳酸氢盐缓冲液中用与白蛋白结合的[¹⁴C]油酸进行单次灌注。净摄取量通过肝内¹⁴C标记脂肪酸浓度的跨肝差异与灌注液流速的乘积计算得出，在1分钟内达到稳态，并在整个10分钟灌注期内保持恒定。在0.17 mM [¹⁴C]油酸和0.15 mM白蛋白条件下，每克雌性肝脏的[¹⁴C]油酸提取分数和净摄取量是雄性肝脏的两倍多（分别为0.33±0.03和0.15±0.02，P<0.001；以及218±22和101±15 nmol/g肝脏，P<0.01），[¹⁴C]油酸的总利用和掺入甘油三酯也存在平行差异。在较高的[¹⁴C]油酸浓度（0.34和0.68 mM）下也观察到摄取的显著差异。在所有条件下，雌性肝脏中[¹⁴C]油酸的氧化等于或超过雄性肝脏，这表明掺入甘油三酯和其他甘油脂质的增加并非仅仅是[¹⁴C]油酸在细胞代谢途径中分布差异的结果。这些研究表明，在完整肝脏中，如同在离体肝细胞中一样，长链脂肪酸摄取存在显著的性别差异。这种差异可能部分解释了观察到的性类固醇对肝脏甘油三酯生物合成和极低密度脂蛋白产生的影响。这些摄取差异的机制仍有待确定。-库什兰，M.C.，J.L.戈兰，W - L.马和R.K.奥克纳。单次灌注大鼠肝脏中长链脂肪酸肝脏摄取的性别差异。
