Ursodeoxycholic acid treatment in humans: effects on plasma and biliary lipid metabolism with special reference to very low density lipoprotein triglyceride and bile acid kinetics

Moderate exercise reduces postprandial triacylglycerol concentrations, which are a risk marker for coronary heart disease. The present study sought to determine the qualitative nature of exercise-induced changes in lipid metabolism and their association (if any) with changes in factor VII activation. Eleven normotriglyceridaemic men, aged 51.7±6.1 years (mean±S.D.), participated in two oral fat tolerance tests after different pre-conditions: control (no exercise), and exercise (90 min of brisk walking the day before). Venous blood samples were obtained in the fasted state and for 8 h after ingestion of a high-fat meal (1.32 g of fat, 1.36 g of carbohydrate, 0.30 g of protein and 10 mg of [1,1,1-13C] tripalmitin·kg-1 body mass). Prior exercise reduced postprandial plasma triacylglycerol concentrations by 25±3% (mean±S.E.M.), with lower concentrations in the Svedberg flotation rate (Sf) 20–400 (very-low-density lipoprotein) fraction accounting for 79±10% of this reduction. There was no effect on plasma factor VII coagulant activity or on the concentration of the active form of factor VIIa. Prior exercise increased postprandial serum 3-hydroxybutyrate and plasma fatty acid concentrations, decreased serum postprandial insulin concentrations and increased exogenous (8 h 13C breath excretion of 15.1±0.9% of ingested dose compared with 11.9±0.8%; P = 0.00001) and endogenous postprandial fat oxidation. These data raise the possibility that reduced hepatic secretion of very-low-density lipoprotein plays a role in the attenuation of plasma triacylglycerol concentrations seen after exercise, although it is possible that increased triacylglycerol clearance also contributes to this effect.

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Leptin Augments the Acute Suppressive Effects of Insulin on Hepatic Very Low-Density Lipoprotein Production in Rats

Endocrinology ◽

10.1210/en.2008-1271 ◽

2009 ◽

Vol 150 (5) ◽

pp. 2169-2174 ◽

Cited By ~ 13

Author(s):

Wan Huang ◽

Anantha Metlakunta ◽

Nikolas Dedousis ◽

Heidi K. Ortmeyer ◽

Maja Stefanovic-Racic ◽

...

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Fatty Acid Oxidation ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Saline Control ◽

Acid Oxidation ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Vldl Metabolism

It is well established that leptin increases the sensitivity of carbohydrate metabolism to the effects of insulin. Leptin and insulin also have potent effects on lipid metabolism. However, the effects of leptin on the regulation of liver lipid metabolism by insulin have not been investigated. The current study addressed the effects of leptin on insulin-regulated hepatic very low-density lipoprotein (VLDL) metabolism in vivo in rats. A 90-min hyperinsulinemic/euglycemic clamp (4 mU/kg · min−1) reduced plasma VLDL triglyceride (TG) by about 50% (P < 0.001 vs. saline control). Importantly, a leptin infusion (0.2 μg/kg · min−1) in combination with insulin reduced plasma VLDL-TG by about 80% (P < 0.001 vs. insulin alone). These effects did not require altered skeletal muscle lipoprotein lipase activity but did include differential effects of insulin and leptin on liver apolipoprotein (apo) B and TG metabolism. Thus, insulin decreased liver and plasma apoB100/B48 levels (∼50%, P < 0.01), increased liver TGs (∼20%, P < 0.05), and had no effect on fatty acid oxidation. Conversely, leptin decreased liver TGs (∼50%, P < 0.01) and increased fatty acid oxidation (∼50%, P < 0.01) but had no effects on liver or plasma apoB levels. Importantly, the TG-depleting and prooxidative effects of leptin were maintained in the presence of insulin. We conclude that leptin additively increases the suppressive effects of insulin on hepatic and systemic VLDL metabolism by stimulating depletion of liver TGs and increasing oxidative metabolism. The net effect of the combined actions of insulin and leptin is to decrease the production and TG content of VLDL particles.

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miR-130b is a potent stimulator of hepatic very-low-density lipoprotein assembly and secretion via marked induction of microsomal triglyceride transfer protein

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00276.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. E262-E275 ◽

Cited By ~ 2

Author(s):

Jing Zhang ◽

Ferdous Rastgar Jazii ◽

Mahdi Montazer Haghighi ◽

Danielle Alvares ◽

Lipei Liu ◽

...

Keyword(s):

Lipid Metabolism ◽

Hepg2 Cells ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Microsomal Triglyceride Transfer Protein ◽

Luciferase Reporter ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Transfer Protein ◽

Stimulation Of

miR-130b is a microRNA whose expression is particularly elevated within adipose tissue and in the circulation in diabetic states. Hepatic miR-130b expression has been linked to hepatocellular carcinoma and changes in lipid metabolism. Here, we investigated the role of miR-130b in hepatic lipid homeostasis and lipoprotein export. We observed that overexpression of miR-130b-3p or -5p in HepG2 cells markedly enhanced the secretion of very-low-density lipoprotein (VLDL) particles, enhanced the secretion of [3H]glycerol metabolically labeled triglyceride (TG), and significantly increased the number or the average size of lipid droplets (LDs), respectively. Overexpression of miR-130b also altered the expression of key genes involved in lipid metabolism and in particular markedly increased both mRNA and protein expression levels of microsomal triglyceride transfer protein (MTP). Conversely, the miR-130b inhibitor decreased mRNA levels of MTP and fatty acid synthase ( FAS) in HepG2 cells. However, dual-luciferase reporter assays indicated that MTP is not a direct target of miR-130b-3p. miR-130b overexpression did not alter de novo synthesized TG or the stability and secretion of apolipoprotein B 100. Interestingly, knockdown of phosphatase and tensin homolog ( PTEN) blocked the upregulation of MTP mRNA induced by miR-130b. Finally, miR-130b-induced stimulation of VLDL secretion was also observed in a second hepatocyte cell culture model, immortalized human hepatocytes, confirming the effects observed in HepG2 cells. Overall, these data suggest a potential role for miR-130b in promoting hepatic VLDL assembly and secretion mediated by marked stimulation of MTP expression and TG mobilization. Thus miR-130b overexpression corrects the defect in VLDL production in HepG2 cells.

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Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism

Atherosclerosis ◽

10.1016/j.atherosclerosis.2014.05.418 ◽

2014 ◽

Vol 235 (2) ◽

pp. e147-e148 ◽

Cited By ~ 1

Author(s):

M. Dashti ◽

J. Levels ◽

M. Motazacker ◽

M. Marcel Vries ◽

M. Mahmoudi ◽

...

Keyword(s):

Lipid Metabolism ◽

Human Plasma ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Very Low Density Lipoprotein ◽

Low Density

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Ursodeoxycholic acid increases low-density lipoprotein binding, uptake and degradation in isolated hamster hepatocytes

Biochemical Journal ◽

10.1042/bj2800589 ◽

1991 ◽

Vol 280 (3) ◽

pp. 589-598 ◽

Cited By ~ 19

Author(s):

B Bouscarel ◽

H Fromm ◽

S Ceryak ◽

M M Cassidy

Keyword(s):

Bile Acid ◽

Ursodeoxycholic Acid ◽

Bile Acids ◽

Direct Effect ◽

Specific Binding ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Maximum Effect ◽

Low Density ◽

Ldl Binding

Ursodeoxycholic acid (UDCA), in contrast to both chenodeoxycholic acid (CDCA), its 7 alpha-epimer, and lithocholic acid, enhanced receptor-dependent low-density lipoprotein (LDL) uptake and degradation in isolated hamster hepatocytes. The increase in cell-associated LDL was time- and concentration-dependent, with a maximum effect observed at approx. 60 min with 1 mM-UDCA. This increase was not associated with a detergent effect of UDCA, as no significant modifications were observed either in the cellular release of lactate dehydrogenase or in Trypan Blue exclusion. The effect of UDCA was not due to a modification of the LDL particle, but rather was receptor-related. UDCA (1 mM) maximally increased the number of 125I-LDL-binding sites (Bmax.) by 35%, from 176 to 240 ng/mg of protein, without a significant modification of the binding affinity. Furthermore, following proteolytic degradation of the LDL receptor with Pronase, specific LDL binding decreased to the level of non-specific binding, and the effect of UDCA was abolished. Conversely, the trihydroxy 7 beta-hydroxy bile acid ursocholic acid and its 7 alpha-epimer, cholic acid, induced a significant decrease in LDL binding by approx. 15%. The C23 analogue of UDCA (nor-UDCA) and CDCA did not affect LDL binding. On the other hand, UDCA conjugated with either glycine (GUDCA) or taurine (TUDCA), increased LDL binding to the same extent as did the free bile acid. The half maximum time (t1/2) to reach the full effect was 1-2 min for UDCA and TUDCA, while GUDCA had a much slower t1/2 of 8.3 min. Ketoconazole (50 microM), an antifungal agent, increased LDL binding, but this effect was not additive when tested in the presence of 0.7 mM-UDCA. The results of the studies indicate that, in isolated hamster hepatocytes, the UDCA-induced increase in receptor-dependent LDL binding and uptake represents a direct effect of this bile acid. The action of the bile acid is closely related to its specific structural conformation, since UDCA and its conjugates are the only bile acids shown to express this ability thus far. However, certain agents other than bile acids, such as ketoconazole, have a similar effect. Finally, the studies suggest that the recruitment of LDL receptors from a latent pool in the hepatocellular membrane may be the mechanism by which UDCA exerts its direct effect.

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A role for hepatic leptin signaling in lipid metabolism via altered very low density lipoprotein composition and liver lipase activity in mice

Hepatology ◽

10.1002/hep.26043 ◽

2012 ◽

Vol 57 (2) ◽

pp. 543-554 ◽

Cited By ~ 40

Author(s):

Frank K. Huynh ◽

Ursula H. Neumann ◽

Ying Wang ◽

Brian Rodrigues ◽

Timothy J. Kieffer ◽

...

Keyword(s):

Lipid Metabolism ◽

Lipase Activity ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Leptin Signaling ◽

Lipoprotein Composition

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Effect of in vitro Cultured Anoectochilus formosanus on Lipid Metabolism in Clinical Uses

The American Journal of Chinese Medicine ◽

10.1142/s0192415x07005223 ◽

2007 ◽

Vol 35 (05) ◽

pp. 735-741 ◽

Cited By ~ 1

Author(s):

Xiao-Ming Du ◽

Ning-Yi Sun ◽

Norihiro Furusho ◽

Jun Hayashi ◽

Yukihiro Shoyama

Keyword(s):

Lipid Metabolism ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Serum Levels ◽

Very Low Density Lipoprotein ◽

Low Density ◽

High Cholesterol ◽

Anoectochilus Formosanus ◽

High Triglyceride

A clinical study was performed on the effect of in vitro cultured Anoectochilus formosanus HAYATA on lipid-metabolism. Sixty-six volunteers, including 36 healthy, 14 high-triglyceride-, 11 high-cholesterol- and 5 high-triglyceride- and high cholesterol- subjects, were administrated with A. formosanus (450 mg/day) for 6 months or 12 months. A. formosanus significantly decreased the concentrations of the serum levels of cholesterol, low density lipoprotein and very low density lipoprotein in all volunteers. The results of the present study suggested that A. formosanus might function as a liver activator resulting in improvement of lipid-metabolism.

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