A Role for the Microtubular System in the Release of Very Low Density Lipoproteins by Perfused Mouse Livers

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Normal mouse livers have been perfused in situ and the release of triglycerides in the perfusate has been measured as an index of very low density lipoprotein secretion. Vincristine or colchicine, drugs known to interfere with the microtubular system, were found to inhibit markedly triglyceride release by perfused livers. When used at appropriate concentrations these drugs did not change glucose production, ureogenesis, ATP levels, or oxygen consumption. The uptake and oxidation of fatty acids by livers perfused with either drugs remained unaffected. Labeled oleate incorporation into total triglycerides (i.e. liver plus perfusate) as well as that of labeled amino acids into total proteins were not changed by vincristine or colchicine. The ultrastructure of livers perfused with these drugs appeared normal except that the microtubules could no longer be observed. Concomitantly numerous clusters of vesicles were observed in vincristine- or colchicine-treated livers. In the presence of vincristine (not in that of colchicine) these vesicles were very often seen in close relationship with amorphous masses interpreted as being precipitated microtubular proteins. It is concluded that the functional integrity of microtubules is important for the intracellular movement and eventual release of very low density lipoprotein particles. The additional observation that total protein secretion by the liver was also markedly inhibited by vincristine or colchicine further suggests that microtubules may also play a role in the release of albumin or globulins.