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S Griglio

Publications and source records attributed to S Griglio.

At least 37 records · Page 2Linked to original sources
PubMed1990

Inhibition of hepatic lipase activity impairs chylomicron remnant-removal in rats.

[4-14C]Cholesteryl oleyl ether-labeled chylomicron remnants were injected into rats which received a specific goat antibody against rat hepatic lipase or a control serum. Chylomicron remnant cholesterol ether disappeared from circulation with a significantly higher half-life (2-fold) in antibody-treated rats than in controls (P less than 0.001). Recovered radioactivity in the liver was 2-fold lower in antibody-treated rats (22.8% (n = 6) vs. 45% (n = 4) P less than 0.01). These results clearly show that hepatic lipase may strongly promote chylomicron remnant cholesterol ether uptake by the liver.

Animals↗
PubMed1989

Chylomicron-remnant uptake by freshly isolated hepatocytes. Effect of heparin and of hepatic triacylglycerol lipase.

Chylomicron remnants labelled biologically with [3H]cholesterol were efficiently taken up by freshly isolated hepatocytes during a 3 h incubation in Krebs bicarbonate medium. Their [3H]cholesteryl ester was hydrolysed (74% net hydrolysis), and 0.1 mM-chloroquine could partially inhibit this hydrolysis, provided that hepatocytes were first preincubated for 2 h 30 min at 37 degrees C. This hydrolysis was also measured in preincubated cells with remnants double-labelled (3H and 14C) on their free cholesterol moiety; [3H]cholesterol arising from [3H]cholesteryl ester hydrolysis was recovered in the free [3H]cholesterol pool. A dose-response study showed saturation of remnant uptake at 180 micrograms of remnant protein/10(7) cells. Heparin (10 units/ml) increased remnant uptake by 63% (P less than 0.01), [3H]cholesteryl ester accumulation in the cell pellet by 110% (P less than 0.025) and hepatic lipase activity secreted in the medium by 2.4-fold (P less than 0.01) and by 3.3-fold (P less than 0.01) at the end of the preincubation and incubation periods respectively. Addition of 100 munits of semi-purified hepatic lipase preparation/flask stimulated remnant uptake by 44-69%, and [3H]cholesteryl ester accumulation in the presence of chloroquine by 2.1-fold (P less than 0.025). When hepatic lipase was incubated solely with the remnants, it decreased their triacylglycerol and phospholipid contents by 24% and 26% respectively. Thus freshly isolated hepatocytes may be used to study chylomicron-remnant uptake. Hepatic lipase, which seems to underly the stimulating effect of heparin, facilitates remnant uptake in vitro, and this could be mediated by at least one (or both) of its hydrolytic properties.

Animals↗
PubMed1988

Influence of genetic obesity and of fat-feeding on hepatic FABP concentration and activity.

When lean and obese Zucker rats were fed a low-fat diet (6.5 percent lipid-derived energy) their hepatic fatty acid binding protein (FABP) concentrations and activities were comparable. After 18 days of fat-feeding (57 percent lipids) FABP concentration and activities were significantly increased to the same extent in both genotypes. Thus hepatic FABP levels are subject to modulation by dietary lipids but not by genetic obesity.

Animals↗
PubMed1985

Relationship between lipogenesis, ketogenesis, and malonyl-CoA content in isolated hepatocytes from the obese Zucker rat adapted to a high-fat diet.

The relationship between lipogenesis and ketogenesis and the concentration of malonyl coenzyme A (CoA) was investigated in hepatocytes from adult obese Zucker rats and their lean littermates fed either a control low-fat diet or a high-fat diet (30% lard in weight). With the control diet, lipogenesis--although strongly inhibited in the presence of either 1 mmol/L oleate, 10(-6) mol/L glucagon or 0.1 mmol/L TOFA (a hypolipidemic drug)--remained about fifteen-fold higher in the obese rats than in the lean rats. In contrast, ketogenesis under some conditions (oleate + TOFA) was not significantly lower (30%) as compared with the lean rats. After adaptation to the high-fat diet, lipogenesis was depressed fourfold in the lean rats and ninefold in the obese ones; however its magnitude remained significantly higher in the latter, namely at a value close to that measured in control-fed lean rats. Ketogenesis was comparable in lean and obese rats and much higher in the presence of 1 mmol/L oleate than of 0.3 mmol/L oleate, whereas lipogenesis did not vary with increasing oleate concentration in the medium. Acetyl-CoA carboxylase activity measured in liver homogenates was higher in the obese group, but was stepwise inhibited by increasing concentrations of oleyl-CoA regardless of the diet for both lean and obese rats, thus showing no abnormality of in vitro responsiveness to this inhibitor. With the control diet, hepatocyte malonyl-CoA levels were significantly higher in the obese rats, both in the basal state and after inhibition of lipogenesis by oleate and TOFA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl-CoA Carboxylase↗
PubMed1983

Oleate metabolism in isolated hepatocytes from lean and obese Zucker rats. Influence of a high fat diet and in vitro response to glucagon.

The uptake and metabolism of [1-14C]oleate (0.3 mmol/L) were studied in isolated hepatocytes from lean and obese Zucker rats fed either a control (low-fat) diet or a high-fat diet. With the control diet, [1-14C]oleate uptake was increased by 70% in the obese rats, and fat-feeding decreased this uptake to values comparable to that of their lean littermates. Interestingly, the hepatocyte mean surface area was increased in the obese mutants by 21% with the control diet and by 30% with the high-fat diet. The possible reasons for the differences in oleate uptake are discussed. With the control diet, cells from the obese rats showed a four-fold rise in [1-14C]oleate esterification, while ketogenesis (beta-hydroxybutyrate + acetoacetate production) as well as the radioactive acid-soluble products were greatly depressed. Production of CO2 was very low and similar in both groups of animals. Adaptation to the high-fat diet in the obese rats resulted in a reversal between esterification and oxidation of oleate: the latter became the major metabolic pathway as in the lean rats. The ketogenic capacity was greatly if not completely restored. In the lean animals, glucagon stimulated ketogenesis both in the presence or absence of oleate and decreased [1-14C]oleate esterification. In the obese rats, the hormone exerted a significant ketogenic effect only if oleate was present and did not influence its esterification. The data demonstrate the following abnormalities in the hepatocytes of obese Zucker rats: (1) an enlargement of cell size, (2) an increased oleate uptake, (3) a virtual absence of a ketogenic response to exogenous oleate, and (4) a markedly increased esterification of the latter. The metabolic defects, but not the cell size, appear to be largely corrected by an adaptation to a high-fat diet. The hepatic response to glucagon was decreased in the obese rats at the level of endogenous ketogenesis.

Animals↗
PubMed1983

D-Glucosamine-induced increase of the glycerol-containing lipids in growing cultures of human malignant epithelial cells.

D-Glucosamine was found to inhibit the growth of human malignant epithelial cells SW-839, HT-29, RT-4, and SK-OV-3 in culture in a process that was associated with significant increments in glycerol-containing lipids. Each cell line had a different sensitivity to the drug, but all four cell lines shared the same features in their response, i.e., dose-dependent (at concentrations of 1, 5, and 10 mM), noncytotoxic reductions in growth (minimum 30%, maximum 70%), and simultaneous 1.5-fold to sevenfold increases in lipid contents. Cells regained their normal growth and lipid patterns when glucosamine was removed. Glucosamine did not modify the lipid contents of cells in the late phase of culture when growth was minimal.

Adenocarcinoma↗
PubMed1982

Intestinal very low density lipoprotein secretion in rats fed various amounts of fat.

1. The effect of a high-fat diet (30% fat by wt.) on intestinal very low density lipoprotein (VLDL) secretion was studied in male rats after specific inhibition of hepatic VLDL secretion by dietary orotic acid. Total VLDL secretion (from liver and intestine) was measured in animals not receiving orotic acid. 2. Fat-feeding resulted in a 32% decreased post-Triton secretion of total serum VLDL triacylglycerols as compared to a control (low fat) diet. Concomitantly, a large stimulation of post-Triton intestinal VLDL triacylglycerols secretion was measured in fat-fed rats. Thus, the major part (64%) of circulating triacylglycerols transported as VLDL originated from the intestine in these animals, leading presumably to an increased secretion of intestinal apolipoproteins. 3. Intestinal VLDL and chylomicron secretion rates increased with the amount of fat in the diet (7, 13, 20 or 30% fat by wt.). Whereas the chylomicron secretion was linearly related to the dietary fat content, the relationship between intestinal VLDL secretion and fat content of the diet was sigmoidal. The highest stimulation of intestinal VLDL formation was observed within a narrow range of dietary fat content (between 10 and 20%).

Animals↗
PubMed1981

Very-low-density-lipoprotein secretion by isolated hepatocytes of fat-fed rats.

The very-low-density-lipoprotein secretion rate of isolated hepatocytes obtained from rats fed a high-fat diet was half that of cells from control animals. In fat-fed rats, the initial cellular uptake of [l-14C]oleate in vitro was decreased by 25%, its esterification to triacylglycerols and phospholipids by 50% and its incorporation into very-low-density-lipoprotein triacylglycerols by 70%. Exogenous oleate was not the main precursor of very-low-density lipoproteins in these animals. Lipogenesis, a minor source of very-low-density lipoproteins with the control diet in our experimental conditions, was inhibited by 84% after fat-feeding. A short-term inhibition of lipogenesis in vitro did not result in a decrease in very-low-density-lipoprotein secretion rate. The results suggest that fat-feeding decreased availability of exogenous as well as endogenous fatty acids for synthesis of very-low-density lipoproteins.

Animals↗
PubMed1980

Effect of a high-fat diet on rat very low density lipoprotein secretion.

1. Very low density lipoprotein (VLDL) secretion rates were studied on rats adapted to a high-fat diet (71% calories as lard) for 3-4 weeks, compared to control (starch-fed) rats. 2. Experiments were performed at 14.00 h, at which time all animals had the same circulating free fatty acids. Fat-fed rats presented an apparent liver stealosis, a high post-Triton chylomicron secretion, but a 40% decreased VLDL secretion. 3. Injection of [1-14C]palmitic acid showed that the tracer was incorporated less in liver triacylglycerols of the fat-fed rats, presumably because of an enhanced ketogenesis. Secretion of labelled VLDL-triacylglycerols in 1 h was diminished 5-fold, even after a correction for the lower hepatic esterification. 4. Two complementary experiments were carried out, with the following results: at 08.00 h, when serum free fatty acid concentrations were comparable in both groups of rats [5,10], post-Triton VLDL secretion was diminished by 45% in the fat-fed rats; at 20.00 h, the fat-fed rats had significantly elevated plasma free fatty acids [5,10], but their VLDL secretion was the same as in control rats. 5. So it appears that in fat-fed rats circulating free fatty acids do not stimulate VLDL secretion as expected. It is suggested that the decreased VLDL secretion with the high-fat diet may result from inhibition of hepatic lipogenesis.

Animals↗
PubMed1979

Diurnal variations of plasma lipoproteins and liver lipids in rats fed starch sucrose or fat.

The incidence of the dietary source of energy on lipid transport and accumulation was investigated over a full nycthemeral cycle in adapted rats fed ad libitum. Starch, sucrose and lard were compared. Lipoprotein composition of the plasma, liver and plasma lipids and insulinemia were analyzed every 3 hours over 24 hours. The pattern of VLDL concentration was dependent on the nature of the energetic substrate. Feeding starch resulted in a remarkable stability of lipoproteins, liver and plasma lipids, despite clearcut diurnal variations in plasma non esterified fatty acids, insulinemia and liver glycogen. In sucrose-fed rats VLDL rose to a sharp maximum in the post prandial period (9-12:00) and were totally cleared by 18:00. In fat-fed rats, HDL were elevated during the night, suggesting a possible stimulation of their synthesis by dietary fat in the intestine. LDL were constantly elevated with peak values at 21:00 while VLDL were very low, even at night, despite elevated levels of non-esterified fatty acids. It is concluded that, in animals adapted to a high fat-diet, a high level of circulating non esterified fatty acids is not sufficient to promote the synthesis of VLDL. The main regulating factor appears to be the intensity of hepatic lipogenesis which is stimulated by sucrose and inhibited by lard. No correlation was found between variations in plasma VLDL and insulinemia.

Animals↗
PubMed1977

Diurnal changes in plasma and liver lipids and lipoprotein lipase activity in heart and adipose tissue in rats fed a high and low fat diet.

In order to evaluate a) the respective roles of adipose and muscle lipoprotein lipase (LPL) in the clearing of alimentary lipemia and b) the role of the resulting nonesterified fatty acids (NEFA) in controlling hepatic ketogenesis and liver triglyceride content, a number of parameters related to lipid metabolism were studied over the 24 hour period (the dark period being from 1930 to 0730 hours), in rats ad libitum fed either a low-fat (LF) or a high-fat (HF) diet containing respectively 1.1% and 41.5% lard. During spontaneous feeding (from 1500-1800 hours onwards), LPL activity in LF rats increased in adipose tissue and decreased in heart; in rats fed the HF diet for 3 weeks, the postprandial rise in adipose LPL was smaller and there was no decrease in heart LPL before 2100 hours. In HF rats, unlike the LF, feeding resulted in a large increase in circulating NEFA and total ketone concentrations, an increase in liver beta-hydroxybutyrate dehydrogenase activity, and a decrease in hepatic triglyceride content. The findings clearly indicate that in HF rats, muscle LPL controls the postprandial rise in plasma NEFA concentrations, which in turn appear to determine the extent of ketonemia and liver triglyceride changes. The possible control of these metabolic events by insulin is discussed.

Adipose Tissue↗
PubMed1977

Weight and metabolic changes induced by low carbohydrate-high fat diets in man and in rat.

Weight loss and potential toxicity of low carbohydrate-high fat diets were examined in 8 volunteer medical students given either a high fat diet or a high carbohydrate diet for 15 days, as well as in 36 Sprague-Dawley rats fed for 5 weeks a series of low carbohydrate diets (less than 1%), varying in protein and lipid proportions. A weight loss occurred with the low carbohydrate-high fat diets; serum cholesterol level increased in both man and rat; plasma triglycerides rose in man. In rat, we found an increase in hepatic lipid levels as in plasma ketone and non-esterified fatty acid concentrations. These effects seemed to be related to the increase in lipid intake rather than the lack of carbohydrates.

Adipose Tissue↗
PubMed1975

Hepatic triglyceride storage and ketonemia in rats fed high fat diets.

Hepatic triglycerides and ketonemia were studied on young rats fed a carbohydrate diet C or fat diets f (22.5% fat) and F (41.5% fat) for 8-15 days. Rats were sacrificed between 9 and 11 a.m. (1) Triglycerides and ketonemia varied proportionally to the diets but triglycerides were strikingly increased with protein deficient fat diets (10% proteic calories). Weight gains were then most reduced but ketonemia remained unchanged. (2) A 24-hour fasting was sufficient to suppress the excess of triglycerides while ketonemia remained still more elevated after 48 h of fasting in rats previously fed the fat diet F as compared to diet C. (3) During the adaptation to the fat diet F, liver triglycerides and plasma non-esterified fatty acids showed an acute rise on day 2 followed by a stabilization to lower levels after 8 days and an increase again with ageing (7 months) while ketonemia was relatively stable. The liver participates in adaptation to a fat diet that induces obesity, by the rapid esterification of the exogenous fatty acids and their output back into the circulation as lipoprotein-triglycerides.

Animals↗