Synthesis and Secretion of Very Low Density Lipoprotein by Cultured Rat Hepatocytes

Weinstein, David; Davis, Roger J.; Engelhorn, Sheldon C.; Steinberg, Daniel

doi:10.1007/978-1-4612-6071-4_36

Cited by 3 publications

(4 citation statements)

References 13 publications

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“…The accumulation of VLDL triglycerides was linear during the course of the experiments and lipolysis and cellular reuptake of VLDL triglycerides were shown to be minimal. Assuming that 15% of liver weight is protein and that the rat liver represents 5% of the total body wt, then the rates of VLDL triglyceride secretion in the present experiments ,ug/h per g wet liver depending on the concentration of glucose) were higher than in liver perfusion studies and similar to the highest reported for rat hepatocytes in suspension (38). Our reported triglyceride secretory rate is 10% higher than that reported by Patsch et al (39) for triglyceride secretion from perfused livers of carbohydrate-induced female rats.…”

Section: Discussionsupporting

confidence: 78%

Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes

Durrington¹,

Newton²,

Weinstein³

et al. 1982

J. Clin. Invest.

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214

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A B S T R A C T The effect of insulin on hepatic triglyceride synthesis and secretion is controversial. Previously, we have described a cell culture system of adult rat hepatocytes that synthesize and secrete very low density lipoprotein (VLDL) triglycerides with small and irreproducible effects of insulin on triglyceride metabolism. To study the primary effects of insulin on hepatic triglyceride metabolism a method was developed utilizing fibronectin-coated culture dishes that allowed adhesion, spreading, and maintenance of hepatocytes for 2-3 d in the absence of serum and insulin. This culture system allowed mass measurements of both cellular and secreted VLDL triglycerides for long time periods after the addition of physiological concentrations of insulin to hormone-free culture medium. In the absence of insulin and after an initial 4 h in culture, the medium was replenished and triglyceride mass was measured at the end of 18-h incubations. VLDL triglyceride accumulated in the culture medium at a linear rate over this time-course with increasing accumulation as the medium glucose concentration was raised from 2.5 to 25 mM glucose (1.77±0.24 to 3.09±0.76 yg triglyceride/mg cell protein per h). There was no apparent significant lipolysis or hepatocellular reuptake of secreted VLDL triglycerides. In the absence of insulin cellular triglyceride levels were unchanged between 3 and 24 h in culture while insulin (50-500 gU/ml) significantly increased cellular triglyceride content at all glucose concentrations tested (0-25 mM). The addition of insulin to the culture medium progressively reduced the rate of VLDL triglyceride secretion accompanied by an increase in cellular triglyceride at insulin concentrations > 50 ,U/ml. Most or all of the observed increase in cell triglyceride content could in all experiments be accounted for by the insulin-induced inhibition of VLDL secretion. Incorporation of [2-3H]glycerol into cellular and VLDL triglycerides as a function of insulin concentration was also measured. Glycerol incorporation data at 20-22 h after plating of the cells closely paralleled the insulin-induced changes in cellular and VLDL triglyceride as determined by mass analysis. The observed effects of insulin occurred at concentrations close to the physiological range and suggest that the direct hepatic effect is to suppress VLDL secretion although the net effect in vivo will clearly reflect many additional accompanying changes.

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Section: Discussionsupporting

confidence: 78%

Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes

Durrington¹,

Newton²,

Weinstein³

et al. 1982

J. Clin. Invest.

Self Cite

214

View full text Add to dashboard Cite

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“…Cholesterol synthesis in the liver cells is increased [24,25]. Mechanisms possibly involved are enhanced ac tivity of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, the key enzyme of cholesterol synthesis Accepted : December 17,1991 [27] and increased availability of mevalonate, a precursor of cholesterol, due to reduced mevalonate catabolism by the kidney [28].The stimulus for increased VLDL cholesterol synthesis appears to be the reduction in serum albumin [10,29], either directly or indirectly via changes in oncotic pressure or plasma viscosity, as recently demonstrated in hepatic cell cultures and nephrotic rats [30,31]. It has been sug gested that there is a nonspecific increase in hepatic pro tein synthesis in response to these factors.…”

mentioning

confidence: 99%

Treatment of Hyperlipidemia in Nephrotic Syndrome: Time for a Change?

Olbricht¹,

Koch²

1992

Nephron

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“…In vitro experiments have confirmed that a low plasma oncotic pressure or viscosity stimulates lipogenesis and albumin synthesis in hepatic cells [15]. However, one in vivo study excluded this possibility, in that plasma viscosity did not correlate with hepatic albumin synthesis [11].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of the disorder in lipoprotein metabo lism has been studied from various aspects. The hypoalbuminemia itself or decrease in plasma viscosity may be a contributory factor [11,15]. Free fatty acids are carried by albumin, and their removal is retarded by hypoalbuminemia [7,16], which may depress LPL activity.…”

mentioning

confidence: 99%

Lipoprotein Derangement during Steroid Treatment in Minimal-Change Nephrotic Syndrome

Tsukamoto

Kokubo²,

Horii³

et al. 1996

Nephron

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To study the pathophysiology of hyperlipidemia in nephrotic syndrome, we compared lipid metabolism in the nephrotic stage (stage 1) and in stage 2, when albuminuria had subsided, in 11 patients with minimal-change disease treated with corticosteroid. High-density lipoprotein (HDL) levels were decreased and HDL contained more cholesterol and triglyceride per unit of protein in stage 1 in the patients than in age-matched healthy controls. The urinary protein level was positively correlated only with low-density lipoprotein (LDL) levels, suggesting that the increased albumin clearance stimulated LDL production. Serum cholesterol levels were positively correlated with apolipo-protein E levels and were negatively correlated with lecithin-cholesterol acyltransferase activity in the nephrotic stage; the opposite correlations were seen in controls. Although triglycerides in HDL had normalized at stage 2, triglycerides in LDL and very-low-density lipoprotein did not return toward normal until stage 3, when serum cholesterol levels were normalized.

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Synthesis and Secretion of Very Low Density Lipoprotein by Cultured Rat Hepatocytes

Cited by 3 publications

References 13 publications

Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes

Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes

Treatment of Hyperlipidemia in Nephrotic Syndrome: Time for a Change?

Lipoprotein Derangement during Steroid Treatment in Minimal-Change Nephrotic Syndrome

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