75 research outputs found
Hepatic fatty acid oxidation : activity, localization and function of some enzymes involved
Fatty acid oxidation is an important pathway for energy production
in mammals and birds. In animal tissues the enzymes of fatty
acid oxidation are located in the mitochondrion. Recent reports
suggest that this is not the case in Castor bean endosperm. In this
tissue the enzymes of B-oxidation are localized in a very fragile cell
organelle, called the glyoxysomes .
Fatty acids are transported in the blood complexed to albumin,
or in esterified form as triglycerides and phospholipids,
complexed to protein (lipoproteins). Lipoproteins are synthesized
in the liverand in the intestinal epithelium (chylomicrons). Before
entering the cell these triglycerides are generally hydrolyzed by lipoprotein
lipase, an enzyme activated by heparin and probably present
in the endothelial cells of the capillary wall.
From the foregoing it is evident that fatty acid presented to the
cell for further metabolism is in the form of "free" fatty acid.
Fatty acids cannot participate in any reaction of intermediary
metabolism, before they have been "activated" to their thioester
with CoA. This reaction is necessary for triglyceride and phospholipid
biosynthesis, for acyl interchange between complex lipids, for
chain-elongation reactions and also for oxidative degradation of fatty
acids
Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes
Background. Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. Materials and methods. The effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides < 2.0 mmol L-1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two-step hyperinsulinaemic euglycaemic clamp over 6-7 h. Results. No between-group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (R(s) = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (R(s) = -0.48, P < 0.05) and the HDL triglyceride content was positively (R(s) = 0.64, P < 0.01) correlated with CET. Conclusion. Insulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting-that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus
Dialysis of isolated low density lipoprotein induces a loss of lipophilic antioxidants and increases the susceptibility to oxidation in vitro
We determined the effects of different dialysis conditions on the antioxidant content, duration of the lag phase and oxidation rate of LDL. Dialysis for 22 h resulted in a 56%–66% reduction in the concentrations of β-carotene, lycopene and α-tocopherol. The lag phase of copper-induced oxidation of freshly isolated LDL was considerably longer than that of LDL dialysed for 22 or 44 h. Our data show that dialysis may result in LDL preparations with antioxidant compositions that are not truly representative of freshly isolated lipoproteins
Dietary trans fatty acids increase serum cholesterylester transfer protein activity in man
The average diet may provide some 8–10 g/day of unsaturated fatty acids with a trans double bond. Previous studies showed that dietary trans fatty acids may simultaneously raise low-density lipoprotein (LDL) cholesterol and reduce high-density lipoprotein (HDL) cholesterol. Human plasma contains a protein (CETP) which transfers cholesterylesters from HDL to lipoproteins of lower density. We hypothesized that CETP could play a role in the effect of trans fatty acids on lipoproteins and measured the activity levels of CETP in serum samples from a 9-week study in which 55 volunteers were fed three controlled diets with different fatty acid profiles. Mean activity was 114 (% of reference serum) after consumption of a high trans fatty acid diet, as opposed to 96 after linoleic acid and 97 after stearic acid (P < 0.02). We conclude that the increased activity of CETP may contribute to the rise in LDL cholesterol and the fall in HDL cholesterol seen on diets with high contents of trans fatty acids
Induction of adrenal scavenger receptor BI and increased high density lipoprotein-cholesteryl ether uptake by in vivo inhibition of hepatic lipase
Hepatic lipase (HL) and scavenger receptor type B class I (SR-BI) have
both been implicated in high density lipoprotein (HDL)-cholesteryl ester
uptake in cholesterol-utilizing tissues. Inactivation of HL by
gene-directed targeting in mice results in up-regulation of SR-BI
expression in adrenal gland (Wang, N., Weng, W., Breslow, J. L., and Tall,
A. R. (1996) J. Biol. Chem. 271, 21001-21004). The net effect on
HDL-cholesteryl ester uptake is not known. We determined the impact of
acute in vivo inhibition of rat adrenal HL activity by antibodies on SR-BI
expression and on human and rat HDL-[3H]cholesteryl ether (CEth) uptake in
the adrenal gland. Rat HDL was isolated from rats in which HL activity had
been inhibited for 1 h. The rats were studied under basal conditions (not
ACTH-treated) and after previous treatment with ACTH for 6 days
(ACTH-treated). Intravenous injection of anti-HL resulted in 70% lowering
of adrenal HL activity in both conditions which were maintained for at
least 8 h. In not ACTH-treated rats, inhibition of adrenal HL increased
adrenal SR-BI mRNA (5.2-fold) and mass (1. 6-fold) within 4 h. HL
inhibition resulted in 41% and 14% more adrenal accumulation of human
HDL-[3H]CEth during 4 and 24 h, respectively. The adrenal uptake of rat
HDL-[3H]CEth increased by 68%, 4 h after the antibody injection. ACTH
treatment increased total adrenal HL activity from 3.7 +/- 0.5 milliunits
to 34.0 +/- 17. 2 milliunits, as well as adrenal SR-BI mRNA from 2.9 +/-
0.7 arbitrary units (A.U.) to 86.8 +/- 41.1 A.U. and SR-BI mass from 7.7
+/- 1.8 A.U. to 63.16 +/- 46.7 A.U. The human HDL-[3H]CEth uptake by
adrenals was also significantly increased from 0.58 +/- 0.11% of injected
dose to 7.24 +/- 1.58% of injected dose. Inhibition of adrenal HL activity
did not result in further induction of SR-BI expression and did not affect
human HDL-[3H]CEth uptake. These findings indicate that SR-BI expression
may be influenced by changes in HL activity. HL activity is not needed for
the SR-BI-mediated HDL-cholester
Elevation of plasma phospholipid transfer protein increases the risk of atherosclerosis despite lower apolipoprotein B-containing lipoproteins.
Plasma phospholipid transfer protein (PLTP) transfers phospholipids
between lipoproteins and mediates HDL conversion. PLTP-overexpressing mice
have increased atherosclerosis. However, mice do not express cholesteryl
ester transfer protein (CETP), which is involved in the same metabolic
pathways as PLTP. Therefore, we studied atherosclerosis in heterozygous
LDL receptor-deficient (LDLR(+/-)) mice expressing both human CETP and
human PLTP. We used two transgenic lines with moderately and highly
elevated plasma PLTP activity. In LDLR(+/-)/huCETPtg mice, cholesterol is
present in both LDL and HDL. Both are decreased in
LDLR(+/-)/huCETPtg/huPLTPtg mice (>50%). An atherogenic diet resulted in
high levels of VLDL+LDL cholesterol. PLTP expression caused a strong PLTP
dose-dependent decrease in VLDL and LDL cholesterol (-26% and -69%) and a
decrease in HDL cholesterol (-70%). Surprisingly, atherosclerosis was
increased in the two transgenic lines with moderately and highly elevated
plasma PLTP activity (1.9-fold and 4.4-fold, respectively), indicating
that the adverse effect of the reduction in plasma HDL outweighs the
beneficial effect of the reduction in apolipoprotein B (apoB)-containing
lipoproteins. The activities of the antiatherogenic enzymes paraoxonase
and platelet-activating factor acetyl hydrolase were both PLTP
dose-dependently reduced ( approximately -33% and -65%, respectively). We
conclude that expression of PLTP in this animal model results in increased
atherosclerosis in spite of reduced apoB-containing lipoproteins, by
reduction of HDL and of HDL-associated antioxidant enzyme activities
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