THE HEPATOCELLULAR UPTAKE OF FREE FATTY-ACIDS IS SELECTIVELY PRESERVED DURING STARVATION

Background/Aims: The liver loses protein during fasting. This study sought to determine if hepatic protein loss during fasting selectively preserves functions important to survival such as uptake of fatty acids, which are major energy substrates in that condition. Methods: initial [H-3]oleate uptake and efflux rates in hepatocytes from starved (for 48 hours) and fed male rats were measured in media containing 250 mu mol/L albumin at oleate/albumin ratios of 0.2:1-2:1. Uptake rates of sulfobromophthalein, taurocholate, and glucose were also determined. Results: Initial oleate uptake rate was saturable with respect to unbound oleate concentration. Maximum initial velocity expressed per cell number did not differ between fasted and fed animals, but measured cell volume and estimated surface area were decreased in starved vs. fed hepatocytes (921 +/- 21 vs. 1623 +/- 58 mu m(2), respectively; P< 0.001). Consequently, when expressed per surface area, maximum initial velocity was greater in starved cells (17 +/- 3 vs. 10 +/- 2 [pmol min(-1) mu m(2)] x 10(-7); P < 0.02). Expressed similarly, oleate efflux was also greater from starved hepatocytes and was inhibited by an antibody to plasma membrane fatty acid binding protein (FABP(pm)). FABP(pm) concentration per unit area of plasma membrane also increased in starved hepatocytes (P < 0.05). By contrast, uptake rates of sulfobromophthalein, taurocholate, and glucose by starved hepatocytes were decreased when expressed per cell number and unchanged per unit area. Conclusions: During fasting, the hepatocellular uptake mechanism for oleate is selectively preserved compared with those for sulfobromophthalein, taurocholate, or glucose.