Dependence of the plasma triacylglycerol-lowering effect of fish oil on insulin replacement in streptozotocin diabetic rats.

Streptozotocin diabetic rats, with and without insulin replacement, and sham-injected controls were fed a high-fat (30% of energy) menhaden oil (MO) or corn oil (CO) diet for 2 weeks. After an overnight fast, plasma and livers were collected for analysis of insulin, glucose, triacylglycerol, cholesterol and glucose-6-phosphate dehydrogenase activity. Streptozotocin treatment resulted in decreased plasma insulin and elevated glucose. MO-feeding to insulin-replaced diabetic rats resulted in higher insulin and lower glucose levels compared to the respective CO-fed rats, suggesting decreased hepatic insulin extraction and greater peripheral utilization of glucose with MO. Plasma triacylglycerol and cholesterol, and hepatic glucose-6-phosphate dehydrogenase activity were reduced in MO-fed vs. CO-fed control rats. These effects of MO were prevented in the diabetic rats but were restored by insulin replacement. We conclude from our data that the presence of insulin is required to observe at least some of the effects of fish oil (FO). To explain our observations we propose that many of the effects of FO on hepatic metabolism are mediated by an inhibition of insulin action in the liver, thus providing a possible central mechanism for the regulation of hepatic lipid metabolism by dietary FO.

Reduction in triacylglycerol levels by fish oil correlates with free fatty acid levels in ad libitum fed rats.

Rats were fed (for 2 or 6 wk) purified diets containing lard (LD) or menhaden oil (MO) at two levels of dietary fat, i.e., at 11.5 and 20.8% of energy in the low fat (LF) and the medium fat (MF) diets, respectively. Following the diet period, rats were sacrificed after either an overnight fast or after uninterrupted ad libitum feeding. The studies were designed to investigate the dependence of our previously reported effects of MO, i.e. the reduction of plasma free fatty acid (FFA) levels and accumulation of hepatic triacylglycerols, on the dietary fat concentration and the nutritional state of the animal at the time of sacrifice. Reductions in plasma triacylglycerol and cholesterol levels in MO-fed relative to LD-fed rats were observed under all conditions. FFA levels were consistently reduced by MO-feeding at both dietary fat concentrations, but only when blood was sampled from ad libitum fed rats. Under these conditions there was a significant positive relationship between plasma FFA and triacylglycerol concentrations. Reduction in plasma FFA levels may be an additional mechanism associated with the triacylglycerol-lowering effect of fish oil (FO). The LF and MF MO diets caused a rise in plasma glucose levels with no significant change in insulin concentration, indicating that the reduction of FFA by MO was not related to changes in insulin concentration or insulin sensitivity. The MO diets had no effect on skeletal muscle or epididymal adipose tissue lipoprotein lipase activity, demonstrating that catabolism of triacylglycerol-rich lipoproteins contributes little, if any, to the MO-dependent reductions of plasma triacylglycerol and FFA.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein lipase in rats fed fish oil: apparent relationship to plasma insulin levels.

To investigate the role of lipoprotein lipase (LPL) and hepatic lipase in the triacylglycerol lowering effects of fish oil, rats were fed lard (L), corn oil (CO) or menhaden oil (MO) as the primary fat source in otherwise identical diets. After 2 weeks, soleus muscle LPL differed between groups (MO greater than CO greater than L). Hepatic lipase did not differ between CO- and MO-fed rats but was elevated in L-fed rats. Adipose LPL did not differ between diet groups. Total epididymal fat weight was reduced in MO-fed rats. There was a significant positive correlation between adipose tissue weight and plasma free fatty acids. MO-fed rats had lower plasma insulin levels. Insulin was directly correlated with plasma triacylglycerol and glucose, consistent with a hyperinsulinemic, insulin-resistant state in CO- and L-fed rats, and a protective effect with MO feeding. In addition, insulin was directly correlated with adipose LPL. A negative relationship between soleus muscle LPL and insulin approached significance. Soleus muscle LPL was significantly inversely correlated with triacylglycerol. The data indicate that increased skeletal muscle LPL, in response to MO or a MO-induced decrease in insulin, may contribute to the triacylglycerol-lowering effects of fish oil. Decreased fat weight and adipose LPL and increased soleus muscle LPL and decreased plasma triacylglycerol suggest a shift from fat deposition to oxidation with MO feeding. The lack of response of hepatic lipase to MO feeding suggests that this enzyme does not contribute to the fish oil-stimulated lowering of plasma triacylglycerol via hepatic reuptake of very low density lipoproteins or other triacylglycerol-rich lipoproteins.

Apparent inhibition of hepatic triacylglycerol secretion, independent of synthesis, in high-fat fish oil-fed rats: role for insulin.

Rats were fed Chow (C; low-fat control) or a purified high-fat (30% of calories) low cholesterol diet containing menhaden oil (MO), corn oil (CO) or lard (L) for 2, 4 or 6 weeks. Rats were killed after an overnight fast. MO-fed rats had a larger weight/body weight that was accompanied by a lower mg liver DNA/g liver but unchanged liver DNA/body weight, indicating that hepatomegaly in the MO-fed rats was due to cellular hypertrophy. MO-feeding prevented the rise in plasma triacylglycerol and cholesterol observed with the other high-fat diets. There was a marked progressive accumulation of total liver triacylglycerol in the MO- and CO-fed rats. Plasma insulin was reduced in the MO-fed rats relative to all other groups. There were strong positive relationships between plasma insulin and triacylglycerol and between insulin and cholesterol in the high-fat-fed rats. Total liver glucose-6-phosphate dehydrogenase and malic enzyme activities were reduced by MO-feeding and were directly correlated with plasma cholesterol and insulin. These data are consistent with an apparent inhibition of hepatic triacylglycerol secretion by high-fat fish oil-feeding that is independent of the inhibitory effects on triacylglycerol synthesis. These data suggest a role for insulin in regulating the plasma triacylglycerol and cholesterol concentrations in MO-fed rats.

The neonatal piglet as a model for human neonatal carnitine metabolism.

Investigations concerning carnitine metabolism and possible requirements for exogenous carnitine in human preterm neonates are limited by ethical considerations. The neonatal piglet is a potential animal model for these investigations. Tissue carnitine concentrations were determined in fetuses from cross-bred domestic gilts at stages of gestation corresponding to those of neonates found in neonatal intensive care units. Fetal piglet plasma and red blood cell carnitine levels decreased from approximately 90 d to term. Skeletal muscle carnitine increased from 60 d to term. Temporal changes in fetal carnitine concentrations in plasma, red blood cells and skeletal muscle throughout gestation are similar to the pattern reported by our laboratory for the human neonate. Cardiac muscle carnitine increased earlier than skeletal muscle but also continued to increase to term. Carnitine concentrations in fetal liver, kidney and intestine were maximal at 90 d and decreased until term. Similarities in physiology, metabolism and profiles of tissue carnitine concentration between the newborn piglet and the human neonate indicate that the neonatal piglet is an appropriate animal model for investigations concerning neonatal carnitine metabolism.

Comparative studies of the responses of two strains of rats to an essential fatty acid deficient diet.

A comparative study of two strains of rats to an EFA deficient diet was conducted. Parameters of insulin status in BHE and Sprague-Dawley rats were measured. No differences in growth were observed. The strains differed in their hepatic and adipose tissue response to insulin stimulation of glucose oxidation and conversion to fatty acids. Hepatic tissue from EFA deficient BHE rats converted more glucose to fatty acid under the influence of insulin than their controls while diet had no effect on glucose oxidation. Hepatic tissue from EFA deficient Sprague-Dawley rats oxidized more glucose than their controls but diet did not affect fatty acid synthesis. A reverse of these strain and diet differences was observed in adipose tissue. These results suggest that the genetic heritage of the rat may determine the type of response to EFA deficiency.

Effect on the interaction of dietary carbohydrate and fat on the responses of rats to starvation-refeeding.

The interacting effects of sucrose or starch with corn or coconut oil on the lipogenic responses of rats to starvation-refeeding was studied. Rats were either ad libitum-fed or starved for 48 h and refed for 48 h. Four different diets were used: 65% starch-5% corn oil, 65% starch-5% coconut oil, 65% sucrose-5% corn oil, 65% sucrose-5% coconut oil. Lipogenesis was assessed in two ways: glucose-6-phosphate dehydrogenase (G6PD) activity, malic enzyme (ME) activity and percent liver lipid (expt 1) and tritium (3HOH) incorporation into fatty acids (expt 2). Starved-refed rats had more liver lipid, greater enzyme activity and greater 3H incorporation into fatty acids than ad libitum-fed rats. Sucrose-fed rats had more lipogenic activity than starch-fed rats. Rats fed coconut oil were more lipogenic than rats fed corn oil. There were highly significant correlation coefficients between the enzyme activities (G6PD and ME) and the percent liver lipid and between the enzyme activities and 3H incorporation into fatty acid. Analysis of variance of these data revealed significant dietary effects on these lipogenic responses to starvation-refeeding. We conclude that both dietary carbohydrate and lipid play a significant role in the determination of the magnitude of the lipogenic response to starvation-refeeding.

The effects of dietary zinc deficiency on voluntary alcohol drinking in rats.

The effects of dietary zinc deficiency on voluntary alcohol drinking in rats were examined in three separate experiments. Zinc-deficient rats showed a significantly greater voluntary alcohol intake as compared with the pair-fed controls. In the first experiment there were 14 male Sprague-Dawley rats with 7 controls and 7 who were begun on a zinc-deficient diet (below 2 ppm) at body weight 58-81 g. In the second experiment with 11 male Sprague-Dawley rats, the same diet was begun at 103-107 g. In the last experiment, 11 rats were begun at 120-199 g. Hair zinc measurements documented lower levels in the zinc-deficient rats after 6 weeks on the diet. The data indicate that a zinc-deficient state did increase voluntary alcohol intake in rats. In each experiment, the per cent alcohol consumed declined when a normal diet was given after the 6th week, and the difference was significant in experiments 1 and 3.

Interaction of glucocorticoid and thyroxine in the responses of rats to starvation-refeeding.

The interaction of glucocorticoid (GC) and thyroxine (T4) in the generation of the hepatic enzyme overshoot and lipid response to starvation-refeeding was studied. Male Sprague-Dawley rats were either left intact, or treated with propylthiouracil (PTU), or adrenalectomized (ADX), or ADX and/or PTU treated and treated with GC and/or T4. One-half of each of these treatment groups was fed a 65% glucose diet while the remaining rats were starved for 48 hours and refed the glucose diet for 48 hours. After decapitation, hepatic lipid and glucose-6-phosphate dehydrogenase (G6PD) activity were determined. Rats treated with only PTU had less of an enzyme overshoot than nontreated rats, and the full overshoot response was restored with T4 treatment. ADX rats did not have the typical enzyme overshoot response to starvation-refeeding. However, ADX rats had their overshoot response restored with GC. PTU-treated ADX rats had more of an overshoot response than did ADX rats. When T4 was administered to PTU-treated ADX rats there was less of an enzyme overshoot; however, when both T4 and GC were administered to the PTU-treated ADX rats, the overshoot response was fully restored. The liver lipid response to starvation-refeeding followed a similar pattern except that in PTU-treated rats the liver lipid levels were significantly higher in the starved-refed rats than in the ad libitum-fed rats. These results indicate that T4 and GC play a role in the G6PD and liver lipid response to starvation-refeeding.

Sequential CT scan as a parameter in the management of CNS lesions.

The value of sequential CT scans as a management determinant in various types of CNS lesions is described. Case reports are cited in support of such a contention. The prediction is that in the not too distant future, intraoperative CT scans will be as commonly done as the plain radiographs currently employed.