Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

1990 ◽  
Vol 258 (4) ◽  
pp. E678-E685 ◽  
Author(s):  
S. Lanza-Jacoby ◽  
A. Tabares
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
E Coli ◽  
Inbred Rats ◽  
Peripheral Clearance ◽  
Vldl Triglyceride ◽  
Kinetics Of

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Removal of triacylglycerols from chylomicrons and VLDL by capillary beds: the basis of lipoprotein remnant formation

2007 ◽  
Vol 35 (3) ◽  
pp. 472-476 ◽  
Author(s):  
F. Karpe ◽  
A.S. Bickerton ◽  
L. Hodson ◽  
B.A. Fielding ◽  
G.D. Tan ◽  
...  
Keyword(s):  
Stable Isotopes ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Lipase Activity ◽  
Remnant Lipoproteins ◽  
Triacylglycerol Content

The triacylglycerol content of chylomicrons and VLDL (very-low-density lipoprotein) compete for the same lipolytic pathway in the capillary beds. Although chylomicron triacylglycerols appear to be the favoured substrate for lipoprotein lipase, VLDL particles compete in numbers. Methods to quantify the specific triacylglycerol removal from VLDL and chylomicrons may involve endogenous labelling of the triacylglycerol substrate with stable isotopes in combination with arteriovenous blood sampling in humans. Arteriovenous quantification of remnant lipoproteins suggests that adipose tissue with its high lipoprotein lipase activity is a principal site for generation of remnant lipoproteins. Under circumstances of reduced efficiency in the removal of triacylglycerols from lipoproteins, there is accumulation of remnant lipoproteins, which are potentially atherogenic.

scholarly journals Nascent very-low-density lipoprotein triacylglycerol hydrolysis by lipoprotein lipase is inhibited by apolipoprotein E in a dose-dependent manner

1997 ◽  
Vol 328 (3) ◽  
pp. 745-750 ◽  
Author(s):  
C. Miek JONG ◽  
E. H. Vivian DAHLMANS ◽  
H. Marten HOFKER ◽  
M. Louis HAVEKES
Keyword(s):  
Lipoprotein Lipase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Control Value ◽  
Dose Dependent ◽  
Deficient Mice

In the present study it was investigated whether apolipoprotein (apoE) can inhibit the lipoprotein lipase (LPL)-mediated hydrolysis of very-low-density-lipoprotein (VLDL) triacylglycerols (TAGs). Previous studies have suggested such an inhibitory role for apoE by using as a substrate for LPL either plasma VLDL or artificial TAG emulsions. To mimic the in vivo situation more fully, we decided to investigate the effect of apoE on the LPL-mediated TAG hydrolysis by using VLDL from apoE-deficient mice that had been enriched with increasing amounts of apoE. Furthermore, since plasma VLDL isolated from apoE-deficient mice was relatively poor in TAGs and strongly enriched in cholesterol as compared with VLDL from wild-type mice, we used nascent VLDL obtained by liver perfusions. Nascent VLDL (d < 1.006) isolated from the perfusate of the apoE-deficient mouse liver was rich in TAGs. Addition of increasing amounts of apoE to apoE-deficient nascent VLDL effectively decreased TAG lipolysis as compared with that of apoE-deficient nascent VLDL without the addition of apoE (63.1±6.3 and 20.8±1.8% of the control value at 2.7 μg and 29.6 μg of apoE/mg of TAG added respectively). Since, in vivo, LPL is attached to heparan sulphate proteoglycans (HSPG) at the endothelial matrix, we also performed lipolysis assays with LPL bound to HSPG in order to preserve the interaction of the lipoprotein particle with the HSPG-LPL complex. In this lipolysis system a concentration-dependent decrease in the TAG lipolysis was also observed with increasing amounts of apoE on nascent VLDL, although to a lesser extent than with LPL in solution (72.3±3.6% and 56.6±1.7% of control value at 2.7μg and 29.6 μg of apoE/mg TAGs added respectively). In conclusion, the enrichment of the VLDL particle with apoE decreases its suitability as a substrate for LPL in a dose-dependent manner.

scholarly journals Lipoprotein lipase stimulates the binding and uptake of moderately oxidized low-density lipoprotein by J774 macrophages

1996 ◽  
Vol 314 (2) ◽  
pp. 563-568 ◽  
Author(s):  
Wendy L. HENDRIKS ◽  
Hans van der BOOM ◽  
Leonie C. van VARK ◽  
Louis M. HAVEKES
Keyword(s):  
Lipoprotein Lipase ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Heparan Sulphate ◽  
Density Lipoprotein ◽  
Cell Types ◽  
Low Density ◽  
Dependent Manner ◽  
Dose Dependent

Lipoprotein lipase (LPL) stimulates the uptake of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) in different cell types, including macrophages, through bridging of LPL between lipoproteins and extracellular heparan sulphate proteoglycans (HSPG). Because macrophages produce LPL and because modified lipoproteins are present in the arterial wall in vivo, we wondered whether LPL also enhances the uptake of oxidized LDL by J774 macrophages. LDL samples with different degrees of oxidation, as evaluated by relative electrophoretic mobility (REM) as compared with native LDL are used, as well as native and acetylated LDL. Addition of 5 μg/ml LPL to the J774 cell culture medium stimulated the binding of both native LDL and moderately oxidized LDL (REM < 3.5) 50–100-fold, and their uptake was stimulated approx. 20-fold. The LPL-mediated binding of native LDL and moderately oxidized LDL was dose-dependent. Preincubation of the cells with heparinase (2.4 units/ml) inhibited the stimulatory effect of LPL, indicating that this LPL-mediated stimulation was due to bridging between the lipoproteins and HSPG. The binding to J774 macrophages of severely oxidized LDL (REM = 4.3) was stimulated less than 3-fold by LPL, whereas its uptake was not stimulated significantly. The binding and uptake of acetylated LDL (AcLDL) were not stimulated by LPL, although the LPL-molecule itself does bind to AcLDL. Measurements of the cellular lipid content showed that addition of LPL also stimulated the accumulation in the cells of cholesteryl ester derived from both native LDL and moderately oxidized LDL in a dose-dependent manner. We conclude that our results present experimental evidence for the hypothesis that LPL serves as an atherogenic component in the vessel wall.

scholarly journals Peroxisome proliferator-activated receptor-γ regulates the expression and function of very-low-density lipoprotein receptor

2010 ◽  
Vol 298 (1) ◽  
pp. E68-E79 ◽  
Author(s):  
Huan Tao ◽  
Srikanth Aakula ◽  
Naji N. Abumrad ◽  
Tahar Hajri
Keyword(s):  
Adipose Tissue ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
And Function

Very-low-density lipoprotein receptor (VLDLR) is a member of the low-density receptor family, highly expressed in adipose tissue, heart, and skeletal muscle. It binds apolipoprotein E-triglyceride-rich lipoproteins and plays a significant role in triglyceride metabolism. PPARγ is a primary regulator of lipid metabolism in adipocytes and controls the expression of an array of genes involved in lipid trafficking in adipocytes. However, it is not known whether VLDLR is also under the control of PPARγ. In this study, we investigated the role of PPARγ in the regulation of VLDLR expression and function in vivo and in vitro. During the differentiation of 3T3-L1 preadipocytes, the levels of VLDLR protein and mRNA increased in parallel with the induction of PPARγ expression and reached maximum in mature adipocytes. Treatment of differentiated adipocytes with PPARγ agonist pioglitazone upregulated VLDLR expression in dose- and time-dependent manners. In contrast, specific inhibition of PPARγ significantly downregulated the protein level of VLDLR. Induction of VLDLR is also demonstrated in vivo in adipose tissue of wild-type (WT) mice treated with pioglitazone. In addition, pioglitazone increased plasma triglyceride-rich lipoprotein clearance and increased epididymal fat mass in WT mice but failed to induce similar effects in vldlr−/−mice. These results were further corroborated by the finding that pioglitazone treatment enhanced adipogenesis and lipid deposition in preadipocytes of WT mice, while its effect in VLDLR-null preadipocytes was significantly blunted. These findings provide direct evidence that VLDLR expression is regulated by PPARγ and contributes in lipid uptake and adipogenesis.

scholarly journals Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism

1999 ◽  
Vol 276 (2) ◽  
pp. E241-E248 ◽  
Author(s):  
Kevin Evans ◽  
Mo L. Clark ◽  
Keith N. Frayn
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Subcutaneous Adipose

We have studied the fate of lipoprotein lipase (LPL)-derived fatty acids by measuring arteriovenous differences across subcutaneous adipose tissue and skeletal muscle in vivo. Six subjects were fasted overnight and were then given 40 g of triacylglycerol either orally or as an intravenous infusion over 4 h. Intracellular lipolysis (hormone-sensitive lipase action; HSL) was suppressed after both oral and intravenous fat loads ( P < 0.001). Insulin, a major regulator of HSL activity, showed little change after either oral or intravenous fat load, suggesting that suppression of HSL action occurred independently of insulin. The rate of action of LPL (measured as triacylglycerol extraction) increased with both oral and intravenous fat loads in adipose tissue ( P = 0.002) and skeletal muscle ( P = 0.001). There was increased escape of LPL-derived fatty acids into the circulation from adipose tissue, shown by lack of reesterification of fatty acids. There was no release into the circulation of LPL-derived fatty acids from skeletal muscle. These results suggest that insulin is not essential for HSL suppression or increased triacylglycerol clearance but is important in reesterification of fatty acids in adipose tissue but not uptake by skeletal muscle, thus affecting fatty acid partitioning between adipose tissue and the circulation, postprandial nonesterified fatty acid concentrations, and hepatic very low density lipoprotein secretion.

Sign in / Sign up

Export Citation Format

Share Document