glycogen and Choline-Deficiency

Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P <.01). Accordingly, fasting and fatty degeneration had a synergistic effect in exacerbating liver injury. Mitochondrial damage was a predominant feature of ultrastructural hepatocyte injury in fasted fatty livers. Glucose supplementation partially prevented the fasting-induced depletion of glycogen and improved the 7-day rat survival to 45%. These data indicate that rat fatty livers exposed to normothermic ischemia-reperfusion injury are much more sensitive to fasting than histologically normal livers. Because glucose supplementation improves both the hepatic glycogen stores and the rat survival, a nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

Topics: Alanine Transaminase; Animals; Choline Deficiency; Fatty Liver; Food Deprivation; Glucose; Glycogen; Liver; Male; Microscopy, Electron; Nutritional Status; Rats; Rats, Wistar; Reperfusion Injury; Survival Rate

Specific insulin binding and glycogen synthesis were studied in control hepatocytes, hepatocytes from rats fed a choline-deficient (CD) diet for 7 to 14 days, and hepatoma cells induced with a CD diet and DL-ethionine in culture. Both the binding affinity and the number of receptors were affected in hepatocytes by the CD diet. The number of receptor sites was 26,000/cell and the dissociation constant (Kd) for the high affinity binding site was 2.6 nM at 30 degrees C, in contrast to the control values of 205,000 sites/cell and 23.2 nM, respectively. In the hepatoma cells, receptor cell number and Kd were further diminished to 6,400 sites/cell and Kd = 1.1 nM. The basal level of glycogen synthesis in control hepatocytes and in CD hepatocytes was similar; however, the basal rate of glycogen synthesis in hepatoma cells was only 16% of that in the control cells. The glycogen synthesis in hepatoma cells was stimulated by insulin, but at a 3-log higher concentration compared to the control cells. This loss of sensitivity to insulin is consistent with the marked decrease in insulin receptors. CD hepatocytes had a decrease in insulin receptors with a concurrent decrease in Kd (increase in binding affinity), such that, sensitivity to insulin did not differ significantly from that of control hepatocytes. However, the maximal stimulation of glycogen synthesis was only 27% that of the control cells. The changes in receptor number and Kd of hepatocytes from rats fed a CD diet may be due to alterations in cell membrane lipid composition and this alteration may be responsible for the enhanced sensitivity of hepatocytes to chemical carcinogens and for the tumor promoting effect of the diet.

Topics: Animals; Choline Deficiency; Glycogen; Insulin; Liver; Liver Neoplasms, Experimental; Male; Rats; Receptor, Insulin

Topics: Animals; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Choline; Choline Deficiency; Dietary Fats; Dietary Proteins; Fatty Liver; Female; Glycogen; Histocytochemistry; Injections, Subcutaneous; Mice

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Choline Deficiency; Electron Transport Complex IV; Esterases; Fats; Fatty Acids; Fatty Liver; Glycogen; Histocytochemistry; Liver; Phospholipids; Protein Deficiency; Rats; Succinate Dehydrogenase; Time Factors