T IlE TRANSPORT and metabolism of various lipids by the liver nmst, of necessity, be regulated by hormonal and neurogenie means in order to maintain "lipid homeostasis" in the intact animal. For the past few years, we have attempted to examine the transport and metabolism of triglycerides (TG) and other lipids by the liver, and to learn how the nutritional state of the alfimal (1), hormones (2,3), drugs and toxic agents, such as CC14 (4,5) affect hepatic lipid transport and metabolism. Recently, we have been concerned with the effects of adrenal hormones, both cortical and medullary, on the transport of fatty acids and triglycerides by the liver, hi order to evaluate these hormonal actions on the liver without the multiple variables inherent in experiments on intact animals, we studied the transport and metabolism of triglycerides and fatty acids in the isolated, perfused rat liver obtained from adrenaleetomized and normal male animals. In recent years it has become apparent that the eatecholamines, epinephrine (E) and norepinephrine (NE), stimulate release of nonesterified fatty acids from fat depots (6,7) and raise the levels of plasma nonesterified fatty acid (NEFA) (7-11). in addition, stimulation of the nerve supply to adipose tissue was observed to increase the release of NEFA (12), whereas denervation increased the lipid content of the depot (13). The neuroendocrine system was further implicated as a regulator of NEFA transport, since it was reported that certain physical and psychological stimuli increased plasma levels of NEFA in man (14,15). These effects of eateeholamines on plasma NEFA levels have been related causally to stimulation of lipolysis of adipose tissue glycerides. In order to ascertain whether the transport and metabolism of lipids by the liver was affected by catecholamines, we investigated the action of E and NE on the transport of fatty acids and triglycerides by the isolated, perfnsed rat liver. It was also desirable that we evaluate the role of the adrenal cortex in hepatic lipid metal)olism. We observed that NEFA uptake, TG release and TG uptake were inhibited by the addition of eatecholamines to the medium perfuslug livers from normal animals. Furthermore, TG release by livers from adrenalectomized rats was severely restricted, but was returned to essentially normal levels by pretreatment of the adrenalectomized rat with cortisone.
ExperimentalNormal male rats (Holtzman Co., Madison, Wise.), weighing 25/)-400 g, maintained on a balanced ration and water ad libit~m, were used as liver donors. Livers also were renioved seven (lays after operation from adrenalectonfized rats that had been receiving 0.9% NaC1 instead of tap water for drinking purposes. Adrenaleetomized rats that were treated with cortisone were kept postoperatively for seven days before ad-ministration of the hormone; thereafter they received three injections of 5 mg cortisone acetate, i.m., and were used on the morning of the tenth day. The perfusion medium consisted of defibrinated rat blood obtained from normal, fed,...
