Luxon B A, Milliano M T, Weisiger R A
Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University Health Sciences Center, St. Louis, MO, USA.
Biochim Biophys Acta. 2000 Sep 27;1487(2-3):309-18. doi: 10.1016/s1388-1981(00)00104-9.
The role of liver cytosolic fatty acid binding protein (L-FABP) in fatty acid transport and metabolism is unclear. Female liver contains substantially more L-FABP than male liver. Female liver also has a different fatty acid transport phenotype, including more rapid uptake, efflux and cytoplasmic transport. However, it is not known if the greater levels of L-FABP are responsible for these differences. We therefore determined whether increasing L-FABP using clofibrate causes male liver to acquire a female transport phenotype. The multiple indicator dilution (MID) method was used to estimate the rate constants for influx, efflux and cytoplasmic diffusion of palmitate in isolated perfused rat livers. Clofibrate treatment increased cytosolic concentrations of L-FABP 4.2+/-0.8-fold, the rate of cytoplasmic diffusion of palmitate 4.3+/-1.7-fold, and the steady-state palmitate extraction 1.5+/-0.3-fold (mean+/-S.E.). Influx and efflux constants were both increased (by 44% and 79%, respectively) to levels typical of female livers. These data suggest that clofibrate-induced elevation of cytosolic L-FABP not only stimulates intracellular diffusion but also influx and efflux of fatty acids. Possible mechanisms include reducing fatty acid binding to cytoplasmic membranes, induction of membrane fatty acid carriers, and catalyzing fatty acid exchange between aqueous cytoplasm and the plasma membrane.
肝脏胞质脂肪酸结合蛋白（L-FABP）在脂肪酸转运和代谢中的作用尚不清楚。雌性肝脏中的L-FABP含量显著高于雄性肝脏。雌性肝脏还具有不同的脂肪酸转运表型，包括更快的摄取、流出和胞质转运。然而，尚不清楚L-FABP水平的升高是否是造成这些差异的原因。因此，我们研究了使用氯贝丁酯增加L-FABP是否会使雄性肝脏获得雌性转运表型。采用多指标稀释（MID）法估算离体灌注大鼠肝脏中棕榈酸酯的流入、流出和胞质扩散速率常数。氯贝丁酯处理使L-FABP的胞质浓度增加了4.2±0.8倍，棕榈酸酯的胞质扩散速率增加了4.3±1.7倍，稳态棕榈酸酯提取率增加了1.5±0.3倍（平均值±标准误）。流入和流出常数均增加（分别增加44%和79%）至雌性肝脏的典型水平。这些数据表明，氯贝丁酯诱导的胞质L-FABP升高不仅刺激细胞内扩散，还刺激脂肪酸的流入和流出。可能的机制包括减少脂肪酸与细胞质膜的结合、诱导膜脂肪酸载体以及催化水性细胞质与质膜之间的脂肪酸交换。
