A biochemical mechanism for the depression in hepatic acetate oxidation in fasted, cold-exposed rats.

Exposure of rats to low environmental temperature causes marked changes in their lipide metabolism (l-6). One of the most striking alterations can be seen in rats that have fasted for 1 day at a temperature of O-2” (“cold-fasted” rats). The livers of these animals are heavily infiltrated with fat and contain almost no glycogen. Studies in vitro showed that liver slices prepared from these rats exhibit a severe defect in their ability to form CY02 from acetate-l-V as well as from a number of other carboxyl-labeled short chain fatty acids (6). The addition of glucose to these glycogen-deficient liver slices, however, restores the oxidation of short chain fatty acids to essentially normal values. In contrast to the findings with short chain fatty acids, liver slices from cold-fasted rats show no defect in their ability to form C’402 from the long chain fatty acids, i.e. palmitate-1-CY4, stearate-1-V and oleate-1-V. Furthermore, the addition of glucose to th; incubation medium causes a marked stimulation in the oxidation of the long chain fatty acids by liver slices from these rats. On the other hand, the addition of glucose to the liver slices from the control rats (fed and maintained at 25”) results in a reduction in the oxidation of the long chain fatty acids, a manifestation of the well known sparing action of glucose on oxidation of long chain acids. The mechanism by which glucose promotes fatty acid oxidation in the liver of the cold-fasted rat has been investigated in this laboratory (3, 6). These studies have led to the following conclusions. (a) Some phase of carbohydrate metabolism is essential for a maximal rate of hepatic fatty acid oxidation, and (6) the phase of carbohydrate metabolism involved is not related to the “sparking” action of intermediates of the Krebs’ cycle. How then does carbohydrate metabolism promote fatty acid oxidation? To investigate this mechanism further, it became necessary to work with a simpler system than that of the intact liver cell. A liver homogenate was developed that was capable of oxidizing glucose, carbohydrate intermediates, long chain and short chain fatty acids, and Krebs’ cycle intermediates. This system was used to investigate the mechanism of interaction between carbohydrate metabolism and the stimulation of acetate oxidation as found in hepatic tissues from cold-fasted rats.