The Effect of High-Carbohydrate Diets on Liver Triglyceride Formation in the Rat

“…Also, it was determined that high-carbohydrate diet increased hepatic fat synthesis, caused to the accumulation of triglyceride in the liver, rise of ALT, AST levels, and caused mitochondrial dysfunction in adipose tissue (31)(32)(33)(34)(35)(36)(37)(38).…”

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confidence: 99%

High Fatty Diet Effects on Rat Liver

et al. 2014

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“…It was our intent to modify hepatic VLDL-TG secretion in individual rats, and to observe changes in the content of microtubules and tubulin of hepatocytes from these animals. In this regard, we took advantage of two well documented facts: (a) Liver cells are capable of rapidly responding to the availability of extracellular FFA by increasing FFA uptake and esterification into TG and by increasing the release of this TG in the form of VLDL particles (24); and (b) rats fed diets high in carbohydrates and/or in specific sugars such as sucrose or fructose will become hypertriglyceridemic (21). In this manner, acute and chronic animal models for increased VLDL-TG secretion were developed, and hepatocytes from these rats were examined for evidence of changes in cellular microtubule and/or tubulin content.…”

Section: Discussionmentioning

confidence: 99%

Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content

Reaven¹,

Reaven²

1978

The Journal of Cell Biology

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The fact that colchicine inhibits hepatic secretion of very low density lipoprotein (VLDL) particles has been interpreted to mean that microtubules are involved in hepatic VLDL secretion. To further define this relationship, we have attempted to see if changes in hepatic VLDL secretion are associated with changes in hepatocyte microtubule or tubulin content. Accordingly, hepatic secretion of VLDL was increased in rats, and the hepatocyte content of both microtubules (using quantitative morphometric methods) and tubulin (using a time-decay colchicine binding assay) was determined. In acute experiments, VLDL secretion was increased by perfusion of isolated rat livers for 2 h with varying concentrations of free fatty acids (FFA). Results indicate that hepatic VLDL triglyceride (TG) secretion at perfusate FFA levels of 0.7 /zEq/ml is threefold greater (P < 0.01) than when livers are perfused without added FFA. However, no differences are observed in the content of microtubules in these livers: specifically, microtubules occupy 0.029% of hepatocyte cytoplasm in livers perfused without FFA and 0.030% of cytoplasm in livers perfused with FFA. In chronic experiments, rats were fed for 1 wk with either standard rat chow or a hyperlipidemic (sucrose/ lard) diet. With the experimental diet, plasma triglyceride levels increase threefold over controls, and liver VLDL-TG production, as determined by [3H]glycerol turnover studies, is 55% greater (P < 0.01) than controls. However, microtubules occupy 0.027% of the cytoplasm of hepatocyte cytoplasm whether rats are on standard or hyperlipidemic diets. Furthermore, the tubulin content of isolated hepatocytes does change, and represents 1% of hepatocyte soluble protein, irrespective of diet. These results suggest that increases in hepatic VLDL secretion can occur without any demonstrable change in hepatocyte assembled microtubule or tubulin content, and raise questions as to the role played by microtubules in hepatic VLDL secretion.KEY WORDS microtubule -tubulin hepatocytes very low density lipoprotein secretion hypertriglyceridemia Very low density lipoproteins (VLDL) are important secretory products of the liver (4,7,8,18).Although the pathway of synthesis, intracellular transport and secretion of these particles has been well defined, the factors regulating their intracellular translocation and secretion are still largely unknown. However, circumstantial evidence has led to the suggestion that microtubules are in-J. CELL BIOLOGY 9 The Rockefeller University Press 9 0021-9525/78/0601-073551.00 735on May 12, 2018 jcb.rupress.org Downloaded from

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“…The fed liver, which esterifies considerable amounts of FFA, secretes more triglycerides than the fasted liver, which preferentially oxidizes the incoming fatty acids (33). Moreover, sucrose feeding, which enhances esterification, also causes enhanced rates of triglyceride secretion (34,35).…”

Section: Methodsmentioning

confidence: 99%

Effect of sulfonylureas on triglyceride metabolism in the rat liver: possible role of the lysosomes in hepatic lipolysis.

Debeer¹,

Thomas²,

Mannaerts³

et al. 1977

J. Clin. Invest.

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A B S T R A C T It has been suggested previously that chlorpropamide and other hypoglycemic sulfonylureas interfere with hepatic triglyceride breakdown. Since ketogenesis from endogenous hepatic lipid stores is a measure of hepatic triglyceride hydrolysis, ketogenesis derived from endogenous lipids as well as ketogenesis derived from exogenously added isotopic oleate was determined in isolated hepatocytes from fasted rats in an attempt to identify the nature of the direct effects of sulfonylureas on hepatic lipid metabolism. Ketogenesis from endogenous lipids was inhibited by 1 mM chlorpropamide, while ketone production from exogenous oleate did not change. The effect of chlorpropamide on hepatic triglyceride metabolism was further studied in the isolated perfused liver of normal rats in the presence of a continuous [3H]oleate infusion and in isolated liver cells incubated in the presence of [3H]oleate. In liver perfusion experiments, 1 mM chlorpropamide enhanced the incorporation of tritium into triglycerides (but not other lipid classes) and increased both liver triglyceride content and triglyceride secretion. Using isolated cells similar effects could be demonstrated at 0.5 mM chlorpropamide.Chlorpropamide, tolbutamide, and carbutamide, all of which inhibited endogenous ketogenesis in isolated liver cells, also inhibited lysosomal triglyceride lipase activity in rat liver homogenates. The drugs were not inhibitory towards alkaline lipase activity.Demethylglycodiazin (2-benzolsulfonamido-5-(,8-hydroxyethoxy The reduction in endogenous ketogenesis, the enhanced accumulation of liver triglycerides, and the stimulation of hepatic triglyceride output by chlorpropamide are ascribed to an interference of the drug with hepatic triglyceride breakdown. The present results also suggest that the lysosomes play a significant role in hepatic lipolysis. INTRODUCTIONFor the last two decades hypoglycemic sulfonylureas have been widely used in the oral treatment of maturity onset diabetes. In addition to stimulating insulin secretion, a variety of extrapancreatic effects have been ascribed to these drugs, amongst which is a direct antiketogenic action on the liver (1-4). Although the antiketogenic effect of the sulfonylureas seems to be well established, the site of their inhibitory action is less clear. Hasselblatt (2) has shown that glycodiazin' and tolbutamide inhibit ketogenesis from endogenous hepatic lipids but not from an exogenously added tracer amount of [1-14C]palmitate in liver slices. Similarly, experiments carried out in our laboratory (3, 4) have demonstrated that the antiketogenic effect of chlorpropamide and carbutamide in the isolated rat liver perfused with a fatty acid-free medium largely disappears upon addition of octanoic or oleic acid to the perfusion medium.The main difference between ketogenesis from endogenous lipids vs. ketogenesis from exogenous fatty acids is that in the former case, hepatic 1 Glycodiazin belongs to the sulfonamidepyrimidine group which is structurally related to the sulfonylurea ...

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The Effect of High-Carbohydrate Diets on Liver Triglyceride Formation in the Rat

Cited by 74 publications

References 37 publications

High Fatty Diet Effects on Rat Liver

High Fatty Diet Effects on Rat Liver

Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content

Effect of sulfonylureas on triglyceride metabolism in the rat liver: possible role of the lysosomes in hepatic lipolysis.

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