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Reduction of plasma triglyceride concentration by acute stress in man.

Three different forms of stress all resulted in acute reduction of plasma triglyceride concentrations. Pyrogen reactions in two hypertriglyceridemic men resulted in the lowering of very-low-density lipoprotein (VLDL) triglyceride levels by 93% and 73% due to decreased secretion of this lipoprotein into plasma. More modest reductions in plasma triglycerides were observed after 2-deoxyglucose-induced intracellular glucopenia and insulin-induced hypoglycemia. With hypoglycemia, the lowering of plasma triglyceride concentration correlated significantly with the stimulation of urinary epinephrine output (r = 0.86) but with neither the urinary norepinephrine response nor with the increase in plasma immunoreactive glucagon levels. To further test whether these changes in plasma triglyceride levels were mediated via the sympathetic nervous system, hypoglycemia was evoked by insulin in subjects with traumatic spinal cord transactions. Two such subjects, who demonstrated sympathetic stimulation in response to hypoglycemia, had evidence of reduced VLDL secretion into plasma, while in two who had no evidence of an adrenergic response. VLDL secretion was not inhibited. Thus, acute lowering of plasma triglyceride concentrations by certain forms of stress appears to be mediated via the sympathetic nervous system.

Acute Disease↗

Effects of dietary substitution of mixed amino acids for glucose on the splanchnic metabolism of plasma triglycerides, cholesterol, carbohydrates, and amino acids in conscious fed baboons.

Splanchnic metabolism was studied in the fed state during prolonged constant intravenous administration of tracer amounts of [9,10]-3H palmitic acid and the calculated isocaloric intraduodenal administration (13 mg/min X kg body wt0.75) of either (1) glucose, (2) 15% mixed amino acids and 85% glucose or (3) 45% mixed amino acids and 55% glucose to conscious, restrained female baboons that had been maintained on a similar diet (supplemented in essential nutrients) for the previous 9 days. Secretion of plasma triglycerides from the splanchnic region was quantified from splanchnic flow and radiochemical measurements of transsplanchnic gradients of 3H-labeled free fatty acids and triglycerides. Mean splanchnic secretion of plasma triglycerides increased significantly as the proportion of dietary calories derived from amino acids was varied from 0 to 15 to 45% (mean values 1.1 +/- 0.1, 2.6 +/- 0.2 and 4.2 +/- 0.3 mumol/min kg body wt0.75, respectively, p less than 0.05). Increased triglyceride secretion was attributable to both significantly higher rates of esterification of free fatty acids taken up in the splanchnic region to triglycerides released into hepatic venous blood plasma (mean values 10 +/- 1, 16 +/- 2 and 34 +/- 5%, respectively) and to significantly higher rates of secretion of triglycerides derived from precursors other than free fatty acids. Higher intake of amino acids was also associated with both higher plasma concentrations of cholesterol and higher values for hepatic oxidation of cholesterol to bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Protein metabolism during total parenteral nutrition (TPN) in injured rats using medium-chain triglycerides.

There are metabolic limitations to the infusion of large quantities of dextrose in critically ill patients receiving total parenteral nutrition. Of the alternative, nonprotein lipid sources, medium chain triglycerides (carbon chain length 8 and 10) are more rapidly oxidized and are deposited in the adipose tissue at rates much less than long chain triglycerides. In rats with burn injury receiving hypocaloric (dextrose and amino acids) parenteral feeding, we studied the changes in protein metabolism as a result of increasing the caloric intake by 33% by the addition of either dextrose, a soybean oil emulsion, a medium chain triglyceride emulsion, or a structured lipid emulsion of triglycerides synthesized from safflower oil (40%) and medium chain triglycerides (60%). Changes in body weight, blood glucose concentration, beta-hydroxybutyrate, lactate, amino acids, insulin, albumin, liver protein content, and nitrogen balance were measured during three days of feeding. Whole body leucine kinetics and muscle protein fractional synthetic rate were evaluated using a constant intravenous infusion of L-[1-14C]leucine. The addition of dextrose or soybean oil emulsion produced a significant increase in body weight and liver nitrogen but did not change albumin concentrations or leucine kinetics compared to those of the hypocaloric feeding group. Rats receiving medium chain triglycerides and structured lipid emulsions showed a reduction in branched chain amino acid concentrations and an improvement in serum albumin levels. However, the rats receiving the structured lipid emulsion also showed increased body weight, had a significant decrease in leucine oxidation, and showed a three day cumulative nitrogen balance significantly greater than zero.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Portal v peripheral hyperinsulinemia and very low density lipoprotein triglyceride kinetics.

The effect of subcutaneously delivered insulin on the kinetics of rat plasma triglycerides was compared to that of intraperitoneally delivered insulin. The former route delivered insulin primarily extrahepatically and the latter, intraportally. In comparison to the intraperitoneally delivered insulin, the subcutaneously delivered insulin was associated with a higher peripheral serum insulin, lower serum glucose, lower serum FFA, lower serum triglycerides, and similar rate of triglyceride secretion. The activity of adipose tissue lipoprotein lipase was directly related to the serum insulin concentration. The pattern of serum triglycerides and lipoprotein lipase in the rats receiving subcutaneous insulin suggested that their rate of triglyceride removal exceeded that seen in the rats receiving intraperitoneal insulin. These observations indicate that the route of insulin delivery can influence the balance between the hepatic and extrahepatic effects of insulin on triglyceride kinetics.

Adipose Tissue↗

Increase in intracellular triglyceride synthesis induced by gemfibrozil.

Gemfibrozil is an effective hypotriglyceridemic agent. Its mechanism of action has not been determined with certainty, but it is generally thought to act by virtue of an effect on lipoprotein lipase. However, this study was designed to test the hypothesis that gemfibrozil directly affects intracellular triglyceride synthesis in peripheral cells, and indeed, when added to the medium, gemfibrozil markedly stimulated triglyceride synthesis in cultured human skin fibroblasts. The effect was concentration-dependent, with a maximum effect at a gemfibrozil concentration of 40 micrograms/mL. A marked increase in triglyceride synthesis was observed when either labeled glucose or labeled fatty acid were added to the medium, indicating that the stimulation was substrate-coordinated. The effect was sustained for hours, with an onset of action within minutes. Lineweaver-Burk plots were constructed, and these revealed no apparent change in Km for either oleate or glucose (8.18 +/- 2.97 v 6.40 +/- 2.10 mumol/L for oleate and 0.113 +/- 0.004 v 0.107 +/- 0.051 mmol/L for glucose, control v gemfibrozil, P = NS). By contrast, there was a significant increase in the maximum triglyceride synthetic rate (Vmax) for both oleate and glucose (14.57 +/- 0.01 v 32.66 +/- 1.85 nmol/mg/4 h for oleate and 67.72 +/- 1.22 v 156.77 +/- 17.61 nmol/mg/4 h for glucose, control v gemfibrozil, P < .025). Given the rapid onset in action, these data suggest that gemfibrozil altered the active state of a limiting step in the triglyceride synthetic pathway. The effect of gemfibrozil on triglyceride synthesis was also determined on differentiated human preadipocytes and HepG2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗

Effects of an acute increase in plasma triglyceride levels on glucose metabolism in man.

The aim of the study was to evaluate the effects of an acute increase in triglyceride levels induced by Intralipid (Kabivitrum, Stockholm, Sweden) infusion on forearm glucose uptake, glucose oxidative metabolism, and hepatic glucose production independent of circulating free fatty acid (FFA) levels in man. Six normal subjects underwent three different tests in random order. Each test consisted of a control period of 120 minutes followed by a euglycemic, hyperinsulinemic clamp lasting 120 minutes. In test 1, a high-dose intravenous Intralipid infusion was performed to increase triglyceride and FFA levels. In test 2, heparin (30 U/min) plus low-dose Intralipid infusions were performed to maintain triglyceride at normal levels and increase only FFA levels. Test 3 was performed as a control study. During the 120-minute control period, forearm glucose uptake and hepatic glucose production were not affected by increasing only FFA levels (test 2) or FFA and triglyceride levels (test 1) as compared with the control study. On the contrary, glucose oxidation was significantly decreased as compared with the control study during tests 1 and 2, without a further significant decrease during simultaneously increased FFA and triglyceride levels. Concomitantly, lipid oxidation was similar in tests 1 and 2, at values significantly greater than in test 3. During the euglycemic clamp, forearm glucose uptake and glucose oxidation were significantly lower during tests 1 and 2 than test 3. At variance with the control period, the increase of triglyceride levels during test 1 caused a significant 30% to 40% decrease of both parameters as compared with test 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The use of in vivo-in vitro labeling techniques to study phospholipid fatty acid turnover and fatty acid esterification into triglycerides in adipose tissue of aging mice.

We are interested in membrane phospholipid and triglyceride synthesis and turnover in aging cells. As a preliminary, short-term feasibility study we have used an established in vivo-in vitro technique to estimate the initial rates of [1-14C] palmitate (complexed to albumin) esterification to triglycerides and phospholipids in adipocytes and non-adipocytes in the epididymal fat pads of aging mice (8-92 weeks). We have expressed our data in terms of unit cell, unit triglyceride mass and unit (membrane) phospholipid mass. Fat pad and adipocyte size, cell surface area, and adipocyte volume changes were measured and found to follow the same relations as reported in the literature, with some exceptions in very old mice (retired breeders). Rates of fatty acid esterification to triglycerides were about 100 times faster than those to phospholipids in adipocytes. Aging caused a marked fall in the rates of triglyceride fatty acid formation from added palmitate; thus, the rate of fatty acid esterification to triglycerides fell from 0.75 to 0.13 nequiv. fatty acid per min per fat pad (youngest most active group, cf. oldest group). Esterification of fatty acids into phospholipids in adipocytes of the oldest mice was significantly lower than in those of the young and middle-aged groups. Contamination of adipocytes by non-adipocytes was observed in fat pads from old, but not from young, mice. The non-adipocytes accounted for about half of the phospholipid fatty acid esterification. The rate of phospholipid esterification was so slow in adipocytes (all ages) and so relatively fast in non-adipocytes that further studies of phospholipid fatty acid turnover in adipocytes using this system are not considered feasible, especially as a means for studying removal rates of autoxidized fatty acids from membrane phospholipids in vivo during aging.

Adipose Tissue↗

Decreased removal of triglycerides from the blood--a mechanism for the hypertriglyceridemia in male patients with coronary artery disease.

We determined serum apolipoprotein A I and A II concentrations and triglyceride and cholesterol concentrations in serum lipoprotein density classes in 28 male patients with severe ischaemic heart disease (IHD) and with angiographically verified coronary artery disease (CAD) and in age-matched controls. Both triglyceride and cholesterol concentrations in very low density lipoproteins and in low density lipoproteins were higher in IHD-patients than in the controls. The triglyceride but not the cholesterol concentration in serum was higher in IHD-patients than in the controls. The cholesterol in high density lipoproteins and the serum apolipoprotein A I concentration were lower in IHD-patients than in the controls. At least in part the higher triglyceride concentration in very low density lipoproteins could be attributed to a decreased removal of triglycerides from the blood since the fractional removal rate of an i.v. injected artificial triglyceride emulsion (Intralipid) was slower in IHD-patients than in the controls.

Adult↗

Long-term effects of bezafibrate on in vivo VLDL-triglyceride production in the rat.

Long-term effects of bezafibrate on in vivo production of VLDL-triglyceride were studied in the rat. Bezafibrate given at a daily dose of 30 mg/kg body weight for 14 days produced a decrease not only in triglyceride by 51% but in cholesterol by 28% and phospholipid by 18%. Despite a marked reduction in plasma triglyceride concentrations, there was no significant change in the rate of VLDL-triglyceride secretion from the liver into the circulation between bezafibrate-treated and control animals (1113 +/- 58 and 1234 +/- 63 micrograms/min, respectively). In addition, bezafibrate produced no change in lipid composition in VLDL. These results suggest that bezafibrate enhances triglyceride removal from the circulation, which leads to reduction in plasma triglyceride.

Animals↗

Prostaglandin E2 and prostaglandin F2 regulation of triglyceride levels in uterine smooth muscle from restricted-diet estrous and diestrous rats.

Triglyceride concentrations in uterine strips isolated from estrous and diestrous normal-fed or restricted-diet (50% food intake for 15 days) rats, were measured. Determinations were made immediately following killing (0 min, or postisolation) as well as after a period in glucose-free medium, (60 min or post-incubation) with or without additions. The postisolation levels of triglycerides (0 min) in the uterus from normal-fed estrous animals were lower than in diestrus but in each group did not differ in comparison with postincubation values (60 min), either without additions or in the presence of indomethacin (10-6M). Initial (0 min) tissue triglycerides of estrous and diestrous partially-starved rats were significantly higher than in their respective fed controls and exhibited different modifications depending on the stage of the sex cycle. In estrus, levels remained unaltered at the end of an incubating period without additions and declined in the presence of indomethacin. This influence of indomethacin was not modified by added PGF2 (10(-9)M) but was effectively abolished by PGE2 (10(-9)M). On the contrary, in diestrus, initial triglyceride levels diminished spontaneously following 60 min without additions, this being antagonized by indomethacin or propranolol (10(-6)M). Furthermore, exogenous PGE2 failed to alter the effect of indomethacin whereas PGF2 evoked its abolition. Propranolol, which effectively blocked the spontaneous decrement of triglycerides as did indomethacin, prevented also the influence of PGF2 on the action of indomethacin. The foregoing results are compatible with the notion that the regulation of triglycerides in rat uteri suspended in the absence of exogenous substrate, is affected differently by prostaglandin E2 and F2 alpha depending on the state of the sex cycle. They also suggest that the phenomenon may involve the activation of the beta adrenoreceptors.

Animals↗

The association between circulating white blood cell count, triglyceride level and cardiovascular and all-cause mortality: population-based cohort study.

OBJECTIVES: To examine the individual and combined relationship between elevated white blood cell count (WBC), triglyceride level and cardiovascular and all-cause mortality among older Australians. DESIGN: Prospective population-based cohort study. SETTING: Community in Blue Mountains region, Australia. PARTICIPANTS: 2904 individuals, aged 49-84 years, free of cardiovascular disease and cancer at the baseline examination. MAIN OUTCOME MEASURES: Cardiovascular (n=242) and all-cause mortality (n=575). RESULTS: Elevated WBC count and triglyceride level were found to be associated with cardiovascular and all-cause mortality, independent of several important confounders. Multivariable relative risk [RR] (95% confidence interval [CI]) comparing fourth (6.8 x 10(9) cells/L and above) versus first quartile (4.8 x 10(9) cells/L and below) of WBC count was 2.01 (1.40-2.90) for cardiovascular mortality and 1.68 (1.35-2.09) for all-cause mortality. Multivariable RR (95% CI) comparing fourth (1.98 mmol/L and above) versus first quartile (0.95 mmol/L and below) of triglyceride level was 1.58 (1.08-2.30) for cardiovascular mortality and 1.40 (1.11-1.77) for all-cause mortality. Furthermore, a combined exposure to the fourth quartiles of both WBC count and triglyceride level was found to be related to more than three-fold risk of cardiovascular mortality (RR [95% CI]: 3.15 [2.17-4.57], p-interaction=0.01), independent of traditional risk factors. CONCLUSIONS: Elevated WBC count and triglyceride level were associated with cardiovascular and all-cause mortality among older Australians. These data provide new epidemiological evidence regarding cardiovascular risk stratification using simple, inexpensive, and routinely available measures, suggesting that a combined exposure to both high WBC count and triglyceride level is related to more than three-fold risk of cardiovascular mortality, independent of traditional risk factors.

Aged↗

Microsomal triglyceride transfer protein expression in adipocytes: a new component in fat metabolism.

Microsomal triglyceride transfer protein (MTP) is a carrier of triglyceride essential for the assembly of apolipoprotein (apo)B-containing lipoproteins by the liver and the small intestine. Its role in triglyceride transfer in tissues that do not secrete lipoproteins has not been explored. In particular, MTP would seem to be a candidate for a role in triglyceride metabolism within the adipocyte. To test this hypothesis, we probed adipocytes for the presence of MTP. Immunohistochemical and biochemical studies demonstrate MTP in adipocytes from brown and white fat depots of mice and human, as well as in 3T3-L1 cells. Confocal microscopy revealed MTP throughout 3T3 cells; however, MTP fluorescence was prominent in juxtanuclear areas. In differentiated 3T3 cells MTP fluorescence was very striking around lipid droplets. In vitro lipid transfer assays demonstrated the presence of triglyceride transfer activity within microsomal fractions isolated from rat adipose tissue. In addition, quantitative rtPCR studies showed that MTP expression in mouse white fat depots was approximately 1% of MTP expression in mouse liver. MTP mRNA in differentiated 3T3 cells was approximately 13% of liver expression. Our results provide unequivocal evidence for the presence of MTP in adipocytes and present new possibilities for defining the mechanisms by which triglyceride is stored and/or hydrolyzed and mobilized.

Adipocytes↗

The effects of bitter melon (Momordica charantia) on serum and liver triglyceride levels in rats.

Effects of three different varieties (Koimidori, Powerful-Reishi, and Hyakunari) of bitter melon (Momordica charantia) and those of methanol fraction extract of Koimidori variety on serum and liver triglycerides were studied in rats. Feeding of diets containing either bitter melon or various fractions isolated by organic solvents caused no adverse effects on food intake or growth of rats. When the effect of three different varieties of bitter melon was compared, the Koimidori variety was found to be the most effective in lowering hepatic triglyceride levels as compared to the other two varieties, suggesting a variety-dependent difference in their activity. Furthermore, the active component(s) responsible for the liver triglyceride lowering activity of Koimidori variety was assumed to be concentrated in the methanol fraction, but not in other fractions such as the n-hexane, the acetone, or the residual fraction. The triglyceride lowering activity was furthermore confirmed by the dose-dependent reduction of hepatic triglyceride, resulting the lowest level in rats fed 3.0% supplementation. In these experiments, the effects on serum lipids were marginal. The results of the present and previous studies clearly show that bitter melon, especially Koimidori variety, exhibits a potent liver triglyceride-lowering activity.

Animals↗

Short-term administration of isotretinoin elevates plasma triglyceride concentrations without affecting insulin sensitivity in healthy humans.

The mechanism underlying hypertriglyceridemia-associated insulin resistance in humans remains poorly understood. It has been proposed that hypertriglyceridemia only produces insulin resistance when associated with an increased lipid delivery to muscle. Accordingly, hypertriglyceridemia secondary to a decreased clearance of triglyceride-rich particles should not cause insulin resistance. To verify this hypothesis, we assessed whole body and adipose tissue insulin sensitivity in 15 healthy male volunteers before and after a 5-day administration of isotretinoin (1 mg/kg/d), a vitamin A derivative that decreases the clearance of triglyceride-rich particles. Whole body insulin-mediated glucose disposal (6,6 (2)H(2)glucose), glucose oxidation (indirect calorimetry), lipolysis ((2)H(5) glycerol), and subcutaneous adipose lipolysis (microdialysis) were evaluated during a 3-step hyperinsulinemic euglycemic clamp. Isotretinoin increased plasma triglyceride from 0.97 +/- 0.15 to 1.30 +/- 0.22 mmol/L (P <.02), but did not change whole body insulin-mediated glucose disposal and lipolysis. These observations are consistent with an isotretinoin-induced inhibition of very-low-density lipoprotein (VLDL)-triglyceride clearance. The suppression of endogenous glucose production and the reduction in subcutaneous adipose glycerol concentrations by insulin remained equally unaffected after isotretinoin administration. We conclude that the impaired clearance of triglyceride-rich particles secondary to a 5-day isotretinoin administration does not impair insulin-mediated antilipolysis or glucose disposal. The data support the concept that hypertriglyceridemia-associated insulin resistance develops primarily when triglyceride production is increased.

Adipose Tissue↗

Soluble E-selectin, leptin, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients.

The aim of the present study was to investigate the relationships between insulin resistance and soluble E-selectin, body mass index (BMI), leptin, and serum lipid profile including triglycerides in nonobese Japanese type 2 diabetic patients. A total of 97 nonobese Japanese type 2 diabetic patients aged 43 to 84 years were examined. The duration of diabetes was 11.2 +/- 0.8 years. In conjunction with BMI and fasting concentrations of plasma glucose, serum lipids (triglycerides, total cholesterol, and high-density lipoprotein cholesterol) and serum insulin, soluble E-selectin, and leptin were also measured. The low-density lipoprotein (LDL) cholesterol level was calculated using the Friedewald formula. Insulin resistance was estimated by the homeostasis model assessment. The subjects were divided into 2 groups according to the value of insulin resistance estimated by the homeostasis model assessment. Values greater than 2.5 were indicative of the insulin-resistant state, and values less than 2.5 were indicative of the insulin-sensitive state. The insulin-resistant group had significantly higher levels of E-selectin, leptin, triglycerides, total and LDL cholesterol, and diastolic blood pressure as compared with the insulin-sensitive group. There was, however, no significant difference in age, sex, diabetes duration, BMI, systolic blood pressure, HbA1c, and high-density lipoprotein cholesterol between the 2 groups. Univariate regression analysis showed that insulin resistance was positively correlated to E-selectin (r = 0.305, P = .003), BMI (r = 0.283, P = .006), leptin (r = 0.296, P = .004), HbA1c (r = 0.241, P = .018), serum triglycerides (r = 0.385, P < .001), serum total (r = 0.240, P = .019) and LDL cholesterol (r = 0.254, P = .013) levels, and systolic (r = 0.247, P = .024) and diastolic (r = 0.305, P = .006) blood pressure. Multiple regression analyses showed that insulin resistance was independently predicted by serum E-selectin (F = 18.4), serum leptin (F = 14.0) and serum triglycerides (F = 20.0) levels, which explained 45.0% of the variability of insulin resistance. From these results, it can be concluded that in conjunction with serum triglycerides and serum leptin, serum E-selectin is another important independent factor associated with insulin resistance in nonobese Japanese type 2 diabetic patients.

Adult↗

Brain phospholipid and triglyceride fatty acid content and pattern in Type 1 and Type 2 diabetic rats.

The liver phospholipid and triglyceride content and/or fatty acid pattern differ(s) not solely in normal versus diabetic rats, but also in distinct rat models of diabetes mellitus. The present study reveals that a comparable situation prevails in the brain. Fed and overnight fasted female normal rats (N) and Goto-Kakizaki rats (GK), as well as fed rats rendered diabetic by a prior injection 3 days before sacrifice of streptozotocin (STZ) were examined. The brain phospholipid content, expressed as milligrams of fatty acids per gram wet weight, was comparable in all groups of rats, with an overall mean value of 31.2+/-0.8 (n=22). The GK rats differed from N and STZ rats by lower C18:0/C18:1omega9 and C18:2omega6/C18:3omega6 ratios and a lower C20:5omega3 content of brain phospholipids. The total amount of fatty acids in triglycerides was 7-8 times higher in GK than N and STZ rats. The GK rats differed from N and STZ rats by lower C16:0/C16:1omega7, C18:0/C18:1omega9 and (C16:0+C16:1omega7)/(C18:0+C18:1omega9) ratios in triglycerides. These findings extend to the brain, the knowledge of alterations in phospholipid and triglyceride content and/or fatty acid pattern in GK rats, as compared to N or STZ rats. The former rats indeed displayed: (i) an apparently increased activity of Delta9- and Delta6-desaturases, as suggested by the phospholipid measurements, and a decreased C20:5omega3 content in such phospholipids; (ii) a dramatic increase in brain triglyceride content; and (iii) an increased activity of Delta9-desaturase, as well as elongase, as judged from the triglyceride data.

Adipose Tissue↗

Increased lipolytic activity and high ratio of free fatty acids to albumin in sera from women with preeclampsia leads to triglyceride accumulation in cultured endothelial cells.

OBJECTIVE: The null hypothesis of this study was that the triglyceride accumulation in endothelial cells exposed to sera from preeclamptic women was determined by the presence of triglyceride-rich lipoproteins in the sera. STUDY DESIGN: The accumulation of triglycerides in cultured endothelial cells was studied using incorporation of tritiated glycerol. RESULTS: Triglyceride-rich lipoproteins in the patient sera contributed little to the endothelial triglyceride accumulation. However, sera from preeclamptic women were found to have a higher molar ratio of free fatty acids to albumin compared with sera from women with normal pregnancies (1.6 +/- 0.5 vs 0.9 +/- 0.4, respectively, p less than 0.025). In addition, sera from preeclamptic women, compared with sera from normal pregnancies, showed enhanced lipolytic activity (release of free fatty acids 0.85 +/- 0.29 vs 0.17 +/- 0.16 mmol/ml per 24 hours, respectively; p less than 0.025) that further increased the free fatty acids/albumin ratio. CONCLUSION: Sera from preeclamptic women have both a higher ratio of free fatty acids to albumin and increased lipolytic activity, resulting in enhanced endothelial uptake of free fatty acids, which are further esterified into triglycerides.

Cells, Cultured↗

Increased cellular triglyceride levels in human monocytic and rat smooth muscle cells after lovastatin.

Beta-hydroxy-beta-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce plasma LDL cholesterol by upregulating hepatic LDL receptors. However, their effects on lipid metabolism in extrahepatic cells may also contribute to their therapeutic benefit. We examined the effects of lovastatin (LOV) on cellular lipid levels in the human monocytic Mono Mac 6sr and cultured rat smooth muscle cells. In both cell types, LOV produced a dose-dependent increase in cellular triglycerides. This increase was observed in cells grown in the absence of exogenous lipids in the culture medium, but was more pronounced after additions of oleic acid (50 to 200 microM) and VLDL (50 to 200 microg ml-1). In Mono Mac 6sr cells grown in medium containing 10% delipidated FCS for the last 16 h, the LOV-induced rise in triglyceride levels was completely reversed by 2 mM mevalonic acid and was associated with a decrease in cellular cholesterol. However, when cells were maintained in lipoprotein-replete medium, the LOV-induced rise in triglycerides did not correlate with cellular cholesterol. LOV also reduced cellular cholesterol esterification and increased the synthesis of fatty acids and their incorporation into triglycerides and phospholipids. Increased triglyceride levels were also seen in Mono Mac 6sr cells treated with the lanosterol demethylase inhibitor RS-21607 and the acylcoenzyme A:cholesterol acyltransferase inhibitor SaH 58035. Our findings suggest that the LOV-induced triglyceride accumulation involves changes in intracellular cholesterol pools regulating cellular fatty acid concentrations. Although decreased cholesterol levels in cells participating in plaque formation are beneficial, the impact of the herein described shift in intracellular neutral lipid metabolism on other cellular functions warrants further investigation.

Acetates↗