An enzymatic explanation for dietary induced alterations in hepatic glycerolipid metabolism

Lamb, Robert G.; Fallon, Harold J.

doi:10.1016/0005-2760(74)90104-0

Cited by 73 publications

(35 citation statements)

References 32 publications

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“…These results support the hypothesis that changes in the activity of this enzyme contribute to the overall control of hepatic triacylglycerol synthesis (Mangiapane et al, 1973;Lamb & Fallon, 1974;Fallon et al, 1977;. The hypothesis is also based on the observation that changes in the activity of the phosphohydrolase generally parallel those in the rate of hepatic triacylglycerol synthesis.…”

Section: Resultssupporting

confidence: 82%

“…This is seen after feeding fructose (Lamb & Fallon, 1974;Fallon et al, 1977) and ethanol Vol. 168 and in genetic obesity (Jamdar et al, 1976;Fallon et al, 1977).…”

Section: Resultsmentioning

confidence: 91%

“…The activities of the total microsomal acyl-CoA synthetase (EC 6.2.1.3) and of glycerol phosphate acyltransferase do respond to some physiological stimuli, but the activities do not always correlate well with the overall rates of triacylglycerol synthesis, and the changes, when observed at all, are usually smaller than those for the soluble phosphatidate phosphohydrolase (Fallon & Kemp, 1968;Vavrecka et al, 1969;Aas & Daae, 1971;Mangiapane et al, 1973;Wiegand et al, 1973;Brandes et al, 1973;Lamb & Fallon, 1974;Fallon et al, 1977;; Table 2). The activity of the soluble phosphatidate phosphohydrolase can change rapidly in response to physiological stimuli and parallels the altered rate of triacylglycerol synthesis (Mangiapane et al, 1973;Lamb & Fallon, 1974;Fallon et al, 1977;. This enzyme is in the middle of the pathway of glycerolipid synthesis and could be involved in controlling the branch point leading to the synthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine on the one hand, and the acidic lipids such as phosphatidylinositol on the other.…”

Section: Resultsmentioning

confidence: 99%

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The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver

1978

Biochemical Journal

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1. Rats were injected with a single dose of 35mg of streptozotocin/kg body wt. They exhibited a diabetes that was characterized by glycosuria, polyuria, polydipsia, hyperphagia, hyperglycaemia, increased concentrations of unesterified fatty acids, glycerol and triacylglycerols in the serum and an increased activity of glucose 6-phosphatase in the liver. 2. After 10 weeks the hepatic activities of the microsomal glycerol phosphate acyltransferase, phosphatidate phosphohydrolase, phosphatidate cytidylyltransferase, diacylglycerol acyltransferase, choline phosphotransferase, CDP-diacylglycerol-inositol phosphatidyltransferase and the soluble phosphatidate phosphohydrolase were measured. 3. The only significant changes were an increase in the activity of the soluble phosphatidate phosphohydrolase and a decrease in that of the CDP-diacylglycerolinositol phosphatidyltransferase in the diabetic rats. 4. These results are discussed in relation to the control of glycerolipid synthesis.Diabetes mellitus is characterized by hyperglycaemia, which is often accompanied by glycosuria, and by an increase in the consumption of food and water and in urine output. In severe cases there is ketonaemia, ketonuria and hypertriglyceridaemia. The last is usually caused by an accelerated secretion of very-low-density lipoprotein, and the severity of the hypertriglyceridaemia can be taken as an indication of the adequacy of the control of the diabetes (Nikkila & Kekki, 1973;Nikkila, 1974).In the present study rats were made chronically diabetic by a single injection of streptozotocin. These animals were then used to investigate whether the diabetic state is accompanied by changes in the relative activities of the enzymes responsible for the synthesis ofglycerolipids in the liver. It is hoped that these results will add to our understanding of how glycerolipid synthesis is controlled.

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Section: Resultssupporting

confidence: 82%

“…This is seen after feeding fructose (Lamb & Fallon, 1974;Fallon et al, 1977) and ethanol Vol. 168 and in genetic obesity (Jamdar et al, 1976;Fallon et al, 1977).…”

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

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The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver

1978

Biochemical Journal

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“…VAVRECKA et al (17) reported that fasting caused a decrease in the activity of acyl-CoA glycerol phosphate acyltransferase in liver homogenates, and an increase in the activity of phosphatidate phosphohydrolase in the supernatant fraction of the liver. Though the phosphatidate phosphohydro lase activity may play a key role in the regulation of endogenous TG formation under such conditions as an accelerated liver TG formation (hepatoectomy (18), high carbohydrate intake (19-21)), the observation in the fasting state is difficult to interpret since most investigators have reported a decrease in neutral lipid formation under this situation (7,21). Therefore, control of PC biosynthesis in fasted rats by the phosphorylcholine-glyceride transferase could be expected and, consequently, the activity of this enzyme could affect the synthesis of liver TG in fasted rats, if this enzyme was rate-limiting.…”

Section: Discussionmentioning

confidence: 99%

Glycerolipid metabolism in cellular and subcellular fractions of fasted rat liver.

Imaizumi

Sugano

1975

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryThe effect of overnight fasting on glycerolipids of the rat liver organelles was studied. The concentration of microsomal phospholipids was markedly decreased by fasting, whereas that of mitochondria and whole liver increased significantly. The significant increase due to fasting in the activity of microsomal phosphorylcholine-glyceride transferase appeared to be responsible for the increased concentration of hepatic phospholipid . Th e incorporation by the liver slice of [1-14C] glycerol into PC3 in mito chondria was increased by fasting, while there was no difference in the microsomal fraction containing supernatant. The significant decrease in the relative proportions of oleic and linoleic acids and a significant increase in stearic and arachidonic acids in phos phatidylcholine were observed in the intact liver as well as its subcellular fractions. The possible relationship of these changes after fasting to th e similarity in the incorporation pattern of [l-14C] glycerol into the molecula r species of these glycerolipids was demonstrated .Considerable but equivocal information is available concerning the effect of fasting on the concentration of hepatic lipids in rats (1-6) . In the previous ex periments in which the effect of fasting was examined systematically , we have shown that overnight fasting produces a significant increase in hepatic PC and PE but not TG In the liver of male rats (7) . An attempt to determine the fatty acid composition of hepatic subcellular fractions in fasted rats was done by ALLMA N et al. (3) and ROGERS (6). These investigators were , however, concerned only with total lipids or total phospholipids , and not with each class of glycerolipids in

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“…We have focutsed our attention on the hepatic cytosolic PA phosphohydrolase activity because (a) ouir earlier work demonstrated a marked increase in its activitv in the ketotic diabetic state and the reversal of the activity to control values on insulin treatment of the rat (1), (b) changes in the activity of this enzyme correlated with changes in the rate of TG synthesis in liver; e.g., high carbohydrate feeding (20), diabetes (1,21), a stubtotal hepatectomy (22), alcohol ingestion (10,23), genetic obesity (24), and treatment with lipid-lowering agents (15,16) and (c) Whiting et al (21) observed that the changes in hepatic TG synthesis in diabetes correlated with changes in PA phosphohvdrolase activity of the soluble buit not the microsomal enzynme.…”

mentioning

confidence: 99%

Regulation of hepatic triglyceride synthesis in diabetic rats.

Murthy¹,

Shipp²

1981

J. Clin. Invest.

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A B S T R A C T The syntheses of triglyceride and its precursors were increased when liver homogenates of ketotic diabetic rats were incubated with [U-14C]-glycero 3-phosphate and cofactors. Triolein sonicates produced a concentration-dependent inhibition of the synthesis of both diglyceride and triglyceride, whereas monoolein sonicates had no effect. Rat In studies on the site of inhibition oftriglyceride synthesis in the overall biosynthetic pathway, serum very low density lipoproteins produced a concentrationdependent inhibition of liver cytosolic phosphatidate phosphohydrolase activity. A higher I50 value was obtained with the hepatic enzyme of the diabetic rats. This higher I50 value was reversed to control by insulin treatment of the diabetic rats. These results indicated that the activity of this enzyme was less sensitive to inhibition by very low density lipoproteins in the ketotic diabetic state. The reduced sensitivity ofphosphatidate phosphohydrolase activity to triglyceride inhibition observed in the present studies could explain our previous observation ofan increased rate oftriglyceride synthesis in ketotic diabetic liver homogenates.

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An enzymatic explanation for dietary induced alterations in hepatic glycerolipid metabolism

Cited by 73 publications

References 32 publications

The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver

The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver

Glycerolipid metabolism in cellular and subcellular fractions of fasted rat liver.

Regulation of hepatic triglyceride synthesis in diabetic rats.

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