SEARCH · Search PubMed

Results for “triglycerides”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources

PubMed1981

Regulation of hepatic triglyceride synthesis in diabetic rats.

The syntheses of triglyceride and its precursors were increased when liver homogenates of ketotic diabetic rats were incubated with [U-14C]-glycero 3-phosphate and cofactors. Triolein sonicates produced a concentration-dependent inhibition of the synthesis of both diglyceride and triglyceride, whereas monoolein sonicates had no effect. Rat serum very low density lipoproteins, like triolein sonicates, inhibited the synthesis of diglyceride and triglyceride. Furthermore, the intracellular form of very low density lipoproteins, namely nascent very low density lipoproteins, also inhibited the synthesis of diglyceride and triglyceride. A higher apparent I50 (concentration of inhibitor that produces 50% inhibition of activity) was observed in liver homogenates of ketotic diabetic rats for inhibition of triglyceride or diglyceride synthesis by triolein sonicates, serum very low density lipoproteins, high density lipoproteins, and nascent very low density lipoproteins. Insulin treatment of the diabetic rats reversed the I50 values to control. In studies on the site of inhibition of triglyceride synthesis in the overall biosynthetic pathway, serum very low density lipoproteins produced a concentration-dependent inhibition of liver cytosolic phosphatidate phosphohydrolase activity. A higher I50 value was obtained with the hepatic enzyme of the diabetic rats. This higher I50 value was reversed to control by insulin treatment of the diabetic rats. These results indicated that the activity of this enzyme was less sensitive to inhibition by very low density lipoproteins in the ketotic diabetic state. The reduced sensitivity of phosphatidate phosphohydrolase activity to triglyceride inhibition observed in the present studies could explain our previous observation of an increased rate of triglyceride synthesis in ketotic diabetic liver homogenates.

Animals↗

PubMedDate not supplied

Effect of different energy sources on hepatic triglyceride secretion during parenteral nutrition.

This study examines the effect of parenteral nutrition on hepatic triglyceride secretion in postoperative patients. Five patients received fluids and electrolytes only (D/S), 10 received a 2000-kcal total parenteral nutrition (TPN) formula with 25% of the nonprotein energy from lipid (LIPID-TPN), and 11 received a similar regimen with all of this energy from dextrose (CHO-TPN). After 7 days an intravenous bolus of 3H-glycerol was given and hepatic triglyceride secretion measured from the decay curve of plasma radiolabeled triglyceride content. Plasma triglyceride concentrations were similar in each group. Hepatic triglyceride secretion was 16.3 mg/kg/hr after D/S, 10.7 mg/kg/hr after LIPID-TPN, and 12.2 mg/kg/hr after CHO-TPN (NS). There was no correlation between the rate of hepatic secretion and dextrose intake. Both TPN regimens resulted in significant reductions in plasma concentrations of apoproteins A1 and B but this did not appear to be related to triglyceride secretion rates. Despite the similar rates of hepatic secretion the quantity of labeled glycerol secreted in triglyceride was significantly greater after CHO-TPN (17629 dpm/24 hr) than either D/S (10560 dpm/24 hr) or LIPID-TPN (7264 dpm/24 hr, p less than 0.05), indicating that recycling of exogenous lipid may have occurred after LIPID-TPN. This study indicates that hepatic triglyceride secretion is not suppressed by TPN, irrespective of the energy source, but suggests that the rate of secretion may have an upper limit.

Apoproteins↗

PubMed2000

Variation of candidate genes in triglyceride metabolism.

After more than a decade of study, investigators are grappling for a consensus regarding the relationship between variation in candidate genes and plasma triglyceride concentration. Certain variants of LPL--both rare variants, in the case of loss-of-function mutations in kindreds with chylomicronemia, and common variants, in the case of the D9N and N291S variants--appear to be fairly consistently associated with an elevated plasma triglyceride level. In addition, the variation of the recognition site for Sstl within the 3'-untranslated region of APOC3 has consistently shown an association with a variation in plasma triglycerides. The LPL and APOC3 variants thus have at least a chance in future clinical applications, but this will require more study. Common variants of some other promising candidate genes, such as HL, have not shown as consistent an association with the variation in plasma triglyceride level. Finally, studies of variants of newer candidates, such as the mitochondrial genome, LMNA, and IL-6, indicate that many different genes might be important determinants of plasma triglyceride concentration in the general population. As always, the associations of genes with a complex intermediate trait such as plasma triglyceride level depend upon interactions with modulatory factors such as genetic background and/or secondary genetic effects, in addition to the effects of gender, age, hormone replacement, and postprandial status. A key attribute for increasing confidence in the biologic or potential clinical validity of the associations of candidate gene variation with plasma triglyceride will be the development of assays that will provide a more direct mechanistic link between the genetic variant and the elevated plasma triglyceride.

Coronary Disease↗

PubMed2003

Genome-wide scan on plasma triglyceride and high density lipoprotein cholesterol levels, accounting for the effects of correlated quantitative phenotypes.

BACKGROUND: Plasma triglyceride and high density lipoprotein cholesterol levels are inversely correlated and both are genetically related. Two correlated traits may be influenced both by shared and unshared genes. The power to detect unshared trait-specific genes may be increased by incorporating correlated traits as covariates. The power to localize the shared genes may be improved by bivariate analysis. Univariate genome scans were carried out on triglyceride (high density lipoprotein cholesterol) with and without using high density lipoprotein cholesterol (triglyceride) as a covariate, and bivariate linkage analysis on triglyceride and high density lipoprotein cholesterol using the 330 Framingham pedigrees of the Genetic Analysis Workshop 13 data. The results of five genome scans were compared to determine the chromosomal regions which may harbor the genes influencing variation specific to triglycerides, specific to high density lipoprotein cholesterol, or the covariation of both triglyceride and high density lipoprotein cholesterol. RESULTS: The results of our five genome scans identified some chromosomal regions with possible quantitative trait loci (QTL) that may specifically influence one trait, such as the regions on chromosome 1 (at 1 cM near marker 280we5), on high density lipoprotein cholesterol, or control the covariation of both traits, such as the regions on chromosome 7 (at 169 cM near marker GATA30D09), chromosome 12 (at 3 cM near marker GATA4H03), chromosome 20 (at 49 cM near marker GATA29F06), chromosome 2 (at 146 cM near marker GATA8H05), and chromosome 6 (at 148 cM near marker GATA184A08) on triglyceride and high density lipoprotein cholesterol. The one on chromosome 6 had a LOD score of 3.1 with the bivariate linkage analysis. CONCLUSION: There is strong evidence for a QTL on chromosome 6 near marker GATA184A08 appearing to influence the variation of high density lipoprotein cholesterol and triglycerides in the Framingham population.

Adult↗

PubMed2002

Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia.

Stearoyl-CoA desaturase (SCD) is expressed at high levels in several human tissues and is required for the biosynthesis of oleate (18:1) and palmitoleate (16:1). These monounsaturated fatty acids are the major components of phospholipids, triglycerides, wax esters, and cholesterol esters. Mice with a targeted disruption of the SCD1 gene have very low levels of VLDL and impaired triglyceride and cholesterol ester biosynthesis. In the HYPLIP mouse, a model of hyperlipidemia, there was a 4-fold increase in hepatic SCD activity, a 1.8-fold increase in the desaturation index, and a 2-fold increase in plasma triglycerides. We used the plasma ratio of 18:1/18:0 (the "desaturation index") as an in vivo measure of SCD activity in human subjects. In human subjects with triglycerides ranging from 0.3 to 20 mM, the desaturation ratio accounted for one-third of the variance in plasma triglyceride levels. A 2-fold increase in the desaturation index was associated with a 4-fold increase in plasma triglycerides. In human subjects exposed to a high carbohydrate diet, the desaturation index explained 44% of the variance in triglycerides. We propose that many of the factors that influence plasma triglyceride levels do so by converging upon the regulation of SCD activity.

Animals↗

PubMed1999

Influence of obesity and body fat distribution on postprandial lipemia and triglyceride-rich lipoproteins in adult women.

We know that upper body obesity is associated with metabolic complications, but we don't know how regional body fat distribution influences postprandial lipemia in obese adults. Thus, this study explored the respective effects of android or gynoid types of obesity and fasting triglyceridemia on postprandial lipid metabolism and especially triglyceride-rich lipoproteins. Twenty-four obese and 6 lean normotriglyceridemic women (control), age 24-57 yr, were enrolled. Among obese women with an android phenotype, 9 exhibited normal plasma triglyceride levels (mean: 1.38 mmol/L) (NTAO), and 7 displayed a frank hypertriglyceridemia (mean: 2.40 mmol/L) (HTAO). The 8 patients with a gynoid phenotype had normal triglyceride levels (mean: 1.00 mmol/L) (GO). All were given a mixed test meal providing 40 g triglycerides. Serum and incremental chylomicron triglycerides 0-7 h areas under the curve (AUCs) as well as triglyceride levels in apoB-48-containing triglyceride-rich lipoprotein (TRLs) or chylomicrons were significantly higher in HTAOs and NTAOs than in GOs and controls postprandially. The size of chylomicron particles was bigger in controls and GOs than in HTAOs and NTAOs postprandially. Android obese subjects showed abnormally elevated fasting apoB-48 and apoB-100 triglyceride-rich lipoprotein (TRL) levels. Most abnormalities that were found correlated to plasma levels of insulin and apoC-III. In conclusion, an abnormal postprandial lipid pattern is a trait of abdominal obesity even without fasting hypertriglyceridemia.

Adipose Tissue↗

PubMed2000

Codon-54 polymorphism of the fatty acid-binding protein 2 gene is associated with elevation of fasting and postprandial triglyceride in type 2 diabetes.

Patients with type 2 diabetes are frequently dyslipidemic or hypertriglyceridemic. To assess whether increased intestinal triglyceride input leads to elevated fasting and postprandial triglycerides in type 2 diabetes, we used the codon 54 polymorphism of the fatty acid-binding protein 2 gene, which results in the substitution of threonine (Thr) for alanine and is associated with increased intestinal input of triglyceride. Of the 287 diabetic patients screened, 108 (37.6%) were heterozygous and 31 (10.8%) were homozygous for the Thr-54 allele. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild-type (n = 80), those heterozygous for the Thr-54 allele (n = 57), and those homozygous for it (n = 18) were 2.0 +/- 0.09, 2.7 +/- 0.20, and 3.8 +/- 0.43 mmol/L, respectively. A linear relationship of mean fasting plasma triglyceride levels (r2 = 0.97) between the 3 groups was found. After fat ingestion, the postprandial area under the curve of plasma triglyceride (P = 0.025) and chylomicrons (Sf > 400, P = 0.013) was higher in the Thr-54/Thr-54 (n = 6) than in the wild-type (n = 9). Our results are consistent with the hypothesis that, in type 2 diabetes, increased intestinal input of triglyceride can lead to elevated fasting and postprandial plasma triglycerides.

Alleles↗

PubMed1999

Triglyceride content of bovine oocytes and early embryos.

A microfluorescence technique was used to measure the triglyceride content of a minimum of two bovine oocytes or preimplantation embryos up to the hatched blastocyst stage. Embryos were produced in vitro from abattoir-derived ovaries and grown in medium containing synthetic oviductal fluid, amino acids and BSA (SOFaaBSA medium); 10% fetal calf serum was added to some of the embryos at the four-cell stage. Before maturation, the triglyceride content of oocytes was 59 +/- 1.37 ng and it decreased (P < 0.05) after maturation to 46 +/- 0.85 ng. A decrease in triglyceride content (P < 0.05) was also observed after fertilization with the formation of the two-cell embryo (34 +/- 1.80 ng). In the absence of serum, the triglyceride content remained relatively constant from the two-cell to the hatched blastocyst stage. The triglyceride content of blastocysts produced in vivo was similar (33 +/- 0.70 ng) to that of blastocysts produced in vitro in the absence of serum. In contrast, the triglyceride content of embryos grown with 10% fetal calf serum increased steadily from the 9-16-cell stage to a value in hatched blastocysts (62 +/- 1.14 ng) almost double that in serum-free conditions. These results indicate that triglyceride may act as energy source during bovine oocyte maturation and fertilization and that the presence of serum causes excessive synthesis or accumulation of triglyceride in early embryos.

Animals↗

PubMed2001

Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation.

Studies in Zucker diabetic fatty rats have led to the concept that chronically elevated free fatty acid (FFA) levels can cause apoptosis of triglyceride-laden pancreatic beta-cells as a result of the formation of ceramides, which induce nitric oxide (NO)-dependent cell death. This "lipotoxicity" hypothesis could explain development of type 2 diabetes in obesity. The present study examines whether prolonged exposure to FFA affects survival of isolated normal rat beta-cells and whether the outcome is related to the occurrence of triglyceride accumulation. A dose-dependent cytotoxicity was detected at 5-100 nmol/l of unbound oleate and palmitate, with necrosis occurring within 48 h and an additional apoptosis during the subsequent 6 days of culture. At equimolar concentrations, the cytotoxicity of palmitate was higher than that of oleate but lower than that of its nonmetabolized analog bromopalmitate. FFA cytotoxicity was not suppressed by etomoxir (an inhibitor of mitochondrial carnitine palmitoyltransferase I) or by antioxidants; it was not associated with inducible NO synthase expression or NO formation. An inverse correlation was observed between the percentage of dead beta-cells on day 8 and their cellular triglyceride content on day 2. For equimolar concentrations of the tested FFA, oleate caused the lowest beta-cell toxicity and the highest cytoplasmic triglyceride accumulation. On the other hand, oleate exerted the highest toxicity in islet non-beta-cells, where no FFA-induced triglyceride accumulation was detected. In conditions without triglyceride accumulation, the lower FFA concentrations caused primarily apoptosis, both in islet beta-cells and non-beta-cells. It is concluded that FFAs can cause death of normal rat islet cells through an NO-independent mechanism. The ability of normal beta-cells to form and accumulate cytoplasmic triglycerides might serve as a cytoprotective mechanism against FFA-induced apoptosis by preventing a cellular rise in toxic free fatty acyl moieties. It is conceivable that this potential is lost or insufficient in cells with a prolonged triglyceride accumulation as may occur in vivo.

Animals↗

PubMed2002

Distribution and cardiovascular risk correlates of serum triglycerides in young Japanese adults.

To examine the distribution and cardiovascular risk correlates of serum triglycerides, a cross-sectional population study based on annual health examinations at the workplace was performed in 2199 young Japanese adults aged 23 to 37 years. Triglyceride levels showed significant sex (male > female) differences, and the percentages of those with high triglycerides (> or = 150 mg/dl) were 9.4% for males and 0.8% for females. In terms of conjoint trait of dyslipidemia, 86.1% of males displayed normal levels of both triglycerides (< 150 mg/dl) and high-density lipoprotein (HDL) cholesterol (> or = 40 mg/dl), while 98.7% of females had normal values. Age- and sex-specific triglyceride levels above the 75th percentile (equivalent to 82-116 mg/dl for males and 56-63 mg/dl for females) increased the risk (odds ratio (OR)) for having obesity, hypertension, and hyperuricemia by 2.9 (95% confidence interval (CI)=2.0-4.3),1.7 (CI=1.1-2.9), and 3.0 (CI=1.6-5.9), respectively. The respective ORs for triglyceride levels above the 75th percentile and HDL cholesterol below the 25th percentile (equivalent to 45-49 mg/dl for males and 58-63 mg/dl for females), compared with triglyceride levels the 75th percentile or less and HDL cholesterol levels the 25th percentile or more, were 8.7 (CI=5.8-12.9), 2.2 (CI=1.5-3.3), and 6.0 (CI=3.2-11.5). Our results suggest a threshold effect of triglyceride levels considered as normal on enhanced cardiovascular risk in young Japanese adults, especially in those with low HDL cholesterol levels.

Adult↗

PubMed2000

Effects of triglyceride accumulation on induction of urea synthesis by glucagon and dexamethasone in monolayer cultures of bovine hepatocytes.

Hepatocyte monolayer cultures from two preruminating and two ruminating calves were used to study the effects of triglyceride accumulation on induction of ureagenesis by glucagon plus dexamethasone. Whether hepatocytes from preruminating and ruminating calves respond similarly to triglyceride accumulation and hormonal treatment was also determined. Hepatocyte monolayer cultures were incubated from 24 to 48 h with a physiological mixture of nonesterified fatty acids (NEFA, 0 or 1.5 mM) and a hormone mixture containing glucagon plus dexamethasone (0 or 100 nM of both) added as a 2 x 2 factorial (NEFA x hormones). Ureagenesis was measured at 0, .25, and 5 mM NH4Cl from 48 to 51 h and activities of ornithine transcarbamylase (OTC) and arginase were measured at 48 h. There was no significant age-related interaction for any of the measurements. Therefore, monolayer culture of hepatocytes from preruminating calves provides a reasonable model for studying the effects of glucagon, dexamethasone, and triglyceride accumulation on ureagenesis in the ruminating bovine. Intracellular triglyceride was increased by NEFA (2.3 vs 15.6 +/- 1.9 microg TG/microg DNA, P < .001). Triglyceride-engorged cells exhibited decreased ureagenesis (1.04 vs .87 +/- .135 nmol/(microg DNA x h), P < .05) but had unaltered OTC and arginase activity. Hormone addition did not affect triglyceride accumulation but increased ureagenesis (.70 vs 1.21 +/- .135 nmol/(microg DNA x h), P < .0001). There was no interaction between hormone addition and triglyceride accumulation on ureagenesis. To separate the effects of dexamethasone from that of glucagon on ureagenesis, hepatocyte monolayer cultures from one ruminating and three preruminating calves were used. Hepatocyte monolayer cultures were incubated from 24 to 48 h with glucagon (0 or 100 nM) and dexamethasone (0 or 100 nM) added as a 2 x 2 factorial. Ureagenesis was measured at 0, .25, and 5 mM NH4Cl from 48 to 51 h. Glucagon increased ureagenesis (.77 vs 1.24 +/- .11 nmol/(microg DNA x h), P < .0001). Dexamethasone did not affect ureagenesis, nor was there any interaction between glucagon and dexamethasone. Therefore, glucagon alone was responsible for the induction observed with the mixture of glucagon and dexamethasone. In conclusion, glucagon is able to increase ureagenesis in bovine hepatocytes, and triglyceride accumulation does not interfere with the induction.

Aging↗

PubMed1991

Effects of energy balance on hepatic capacity for oleate and propionate metabolism and triglyceride secretion.

The purpose of this study was to identify conditions that could decrease accumulation of triglyceride in liver, preferably by increasing hepatic secretion of triglyceride-rich lipoproteins. Hepatocytes isolated from lactating goats were incubated in vitro, and the fate of [1-14C]oleate was measured to determine hepatic capacity for various routes of long-chain fatty acid metabolism. The effect of in vivo energy balance and modifications of the nutrients present in the culture media were tested. Addition of linoleic acid, isovalerate, niacin, propionate, or propylene glycol did not affect triglyceride accumulation or secretion. Pyruvate decreased intracellular triglyceride accumulation. Changes in oxidation of oleate through manipulation of carnitine acyl transferase activity did not influence oleate esterification rate. Livers and hepatocytes isolated from goats in negative energy balance contained more lipid and triglyceride. Liver cells from goats in negative energy balance had decreased capacity for converting propionate to glucose with no change in ketogenic capacity as judged by acid soluble product formation from oleate. Hepatocytes from goats in negative energy balance retained less oleate as cell triglyceride with no change in triglyceride export, indicating a decreased net rate of esterification. Lactating goats, either in negative or positive energy balance, demonstrated the same low capacity for export of newly synthesized triglyceride as previously reported for fed wethers.

Animals↗

PubMed1997

Utilization of supplemental triglycerides or free fatty acids by calves from 4 to 10 weeks of age.

Our objectives were 1) to determine the effects of increased availability of 2-monoglycerides from triglyceride digestion on absorption of free fatty acids (FFA) and utilization of nutrients by calves of weaning age and 2) to determine whether absorption of FFA increased with age. Thirty-two male Holstein calves were fed milk replacer until d 28 of age and then were assigned, to one of four treatments: 1) control, 80 g/d of whey protein concentrate in 2 L of water; 2) control plus 120 g/d of lard triglycerides; 3) control plus 90 g/d of lard triglycerides plus 30 g/d of lard FFA (low FFA); and 4) control plus 60 g/d of triglycerides plus 60 g/d of lard FFA (high FFA). Treatments were fed by nipple pail twice daily to maintain closure of the esophageal groove. Intake of calf starter (available continuously) was decreased by supplemental fats and tended to be lower for calves fed high FFA than for those fed low FFA. Digestibilities of total C18 fatty acids and total fatty acids were lower for calves fed triglycerides than for calves fed FFA, but digestibilities were not affected by age. Energy digestibility was greater for fat treatments than for controls and was greater for FFA treatments than for triglycerides, but intakes of digestible energy and metabolizable energy did not differ. Absorbed N was greater for calves on the control treatment than for those on the fat treatments, but retained N and average daily gain did not differ. Digestibility of fatty acids was greater for calves fed mixtures of triglycerides and FFA than for those fed triglycerides alone, but digestibility did not change during wk 6 to 10 of age.

Aging↗

PubMed1975

Mechanism of avian estrogen-induced hypertriglyceridemia: evidence for overproduction of triglyceride.

Relying on methods other than the determination of turnover rate of triglyceride from the curve of plasma triglyceride radioactivity after administration of labeled precursor, we have confirmed that the endogenous hypertriglyceridemia induced by estrogenization of the chick is accompanied by increased production of triglyceride. Chicks estrogenized with diethylstilbestrol became grossly hypertriglyceridemic and had elevated levels of plasma free fatty acid. Within 5 min of administration of labeled palmitate, estrogenized hypertriglyceridemic birds converted approximately 10 times more plasma free fatty acid to hepatic triglyceride than did controls. In addition, 2 hr after intraperitoneal injection of [14-C]acetate or [U-14-C]glucose, the specific activity of very low density lipoprotein triglyceride (VLDL-TG) of estrogenized birds reached or exceeded that of the untreated controls, and the rapid enrichment of the vastly expanded plasma VLDL-TG pool with labeled triglyceride further indicated that increased production of triglyceride occurs with estrogenization. Furthermore, [14-C]acetate incorporation into VLDL-TG was calculated to be 1.6 and 6.6% of the injected dose in estrogenized birds compared with 0.1 and 0.2% in untreated birds. Increased production of plasma VLDL-TG was confirmed by a kinetic study of VLDL-TG metabolism, employing reinjected, endogenously prepared [14-C]triglyceride-labeled VLDL. The fractional turnover rate of VLDL-TG in estrogenized hypertriglyceridemic birds was substantially less than that in untreated controls (0.32 plus or minus 0.03 vs 0.71 plus or minus 0.03/hr), but the total turnover rate was nearly 50 times greater (244 plus or minus 52 vs. 5 plus or minus 1 mg/hr).

Acetates↗

PubMed1992

Myocardial triglyceride turnover during reperfusion of isolated rat hearts subjected to a transient period of global ischemia.

Triglyceride turnover in reperfused/ischemic rat hearts was investigated. Hearts were initially perfused under aerobic conditions for a 1-h "pulse" perfusion with 1.2 mM [1-14C]palmitate to label the endogenous lipid pools, followed by a 30-min period of no-flow ischemia or a 10-min period of retrograde perfusion (control). Hearts were then reperfused under aerobic conditions with buffer containing 1.2 mM [9,10-3H]palmitate. All buffers contained 11 mM glucose and 500 microunits/ml insulin. Rates of endogenous triglyceride lipolysis and synthesis were measured during reperfusion, whereas rates of exogenous palmitate oxidation were measured both prior to ischemia and during reperfusion following ischemia. During reperfusion of ischemic hearts, a 20% increase in exogenous fatty acid oxidation rates was seen compared with pre-ischemic rates. Despite an initial burst of endogenous fatty acid oxidation, no acceleration of steady state endogenous triglyceride lipolysis was seen compared with their nonischemic hearts. In contrast, a significant increase in triglyceride synthesis was observed. Triglyceride turnover was also measured in a series of hearts reperfused following ischemia in the absence of exogenous fatty acids. A significant enhancement of functional recovery was seen compared with hearts reperfused with 1.2 mM palmitate. In addition, a significant increase in fatty acid oxidation from endogenous triglyceride lipolysis was observed. We conclude that the heart quickly recovers its ability to oxidize exogenous fatty acids during reperfusion and that although triglyceride lipolysis is not accelerated during reperfusion of ischemic hearts in the presence of 1.2 mM palmitate, a significant increase in triglyceride synthesis does occur.

Animals↗

PubMed1977

Regulation of triglyceride metabolism in the isotopically prelabeled perfused heart.

Utilization of 14C-prelabeled endogenous triglycerides was studied in isolated perfused working rat hearts. Lipolysis was estimated by the disappearance of 14C-labeled and total triglycerides. Metabolic 14CO2 production was continuously monitored to evaluate triglyceride fatty acid oxidation. Triglyceride utilization was enhanced by an increase in ventricular pressure development as evidenced by a faster rate of triglyceride mobilization and oxidation. Added catecholamines stimulated lipolysis in hearts perfused with glucose-containing buffer but were without effect in the presence of exogenous fatty acids; the latter were shown to be potent and, possibly, direct inhibitors of myocardial lipolysis. Mediation of catecholamine-induced lipolysis by cyclic AMP has not been settled. Dibutyryl cyclic AMP produced only a slight lipolytic effect, although theophylline, a known phosphodiesterase inhibitor, was a potent lipolytic agent. Theophylline may have exerted its lipolytic effect through an alternative mechanism. Hypoxia per se was a strong inhibitor of heart triglyceride utilization. Furthermore, added epinephrine was without effect on triglyceride lipolysis in hypoxic hearts. Thus, cardiac muscle triglyceride utilization is influenced by such factors as mechanical function, exogenous substrates, hormones, and oxygen availability. The mechanisms involved in these areas of regulation need to be resolved.

Animals↗

PubMed1990

Regulation of fatty acid oxidation and triglyceride and phospholipid metabolism by hypolipidemic sulfur-substituted fatty acid analogues.

The mechanisms behind the hypotriglyceridemic effect of 1,10-bis(carboxymethylthio)decane (3-thiadicarboxylic acid) and tetradecylthioacetic acid and the development of fatty liver caused by 3-tetradecylthiopropionic acid (Aarsland et al. 1989. J. Lipid Res. 30: 1711-1718.) were studied in the rat. Repeated administration of S-substituted non-beta-oxidizable fatty acid analogues to normolipidemic rats resulted in a time-dependent decrease in plasma triglycerides, phospholipids, and free fatty acids. This was accompanied by an acute reduction in the liver content of triglycerides and an increase in the hepatic concentration of phospholipids. Mitochondrial fatty acid oxidation was stimulated, whereas lipogenesis was inhibited. The activity of phosphatidate phosphohydrolase decreased while the activity of CTP:phosphocholine cytidylyltransferase increased. These results suggest that the observed triglyceride-lowering effect was due to increased mitochondrial fatty acid oxidation accompanied by a reduction in the availability of the substrate i.e., free fatty acid, along with an enzymatic inhibition (phosphatidate phosphohydrolase). Administration of 3-tetradecylthiopropionic acid led to a drastic increase in the hepatic triglyceride content. Levels of plasma triglyceride phospholipid and free fatty acid also increased. Phosphatidate phosphohydrolase activity was stimulated whereas CTP:phosphocholine cytidylyltransferase was inhibited. Mitochondrial fatty acid oxidation was decreased. These data indicate that the development of fatty liver as an effect of 3-tetradecylpropionic acid is probably due to accelerated triglyceride biosynthesis, which is mediated by an increase in the availability of fatty acid along with stimulation of phosphatidate phosphohydrolase. The results of the present study speak strongly in favor of the hypothesis that phosphatidate phosphohydrolase is a major rate-limiting enzyme in triglyceride biosynthesis. Furthermore, they point out that the biosynthesis of triglycerides and phospholipids might be coordinately regulated. Such regulation is possibly mediated via phosphatidate phosphohydrolase and CTP:phosphocholine cytidylyltransferase. Whether the increase in hepatic phospholipids via increased CDP-pathway accounts for an increase of lipid components for proliferation of peroxisomes (3-thiadicarboxylic acid and tetradecylacetic acid) should be considered.

Animals↗

PubMed1988

The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells.

To study the effect of triglyceride content of low density lipoprotein (LDL) on its physicochemical and biological properties, we have depleted the triglyceride by incubation with hepatic lipase (HL-LDL) and raised the triglyceride by incubation of HL-LDL with very low density lipoprotein and lipoprotein-deficient serum. HL-LDL was taken up by human monocyte-derived macrophages and by human skin fibroblasts at an increased rate compared to untreated LDL. Incubation of the various LDL preparations revealed that cellular LDL degradation as well as LDL-mediated cholesterol esterification were inversely related to the triglyceride content of the LDL preparation. Modification of the triglyceride content of LDL also was associated with changes in the free fatty acid content, but the interaction of the LDL with cells was unaffected by the level of this component. The triglyceride content of LDL was found to be reciprocally related to the number of free lysine amino groups of LDL apolipoprotein B (apoB) which could be labeled with trinitrobenzenesulfonic acid. 13C-Nuclear magnetic resonance (NMR) spectra of native LDL and HL-LDL samples containing [13CH3]2 lysine residues formed by reductive methylation (11-13% modification) showed that the arrangement of apoB lysines is perturbed by the exposure to hepatic lipase. The ratio of labeled lysines with pK 8.9 to those with pK 10.5 exposed on the surface of LDL particles was decreased by about 40% by lipase treatment. These effects are apparently due to changes in local apoB conformation because circular dichroism spectra revealed that the average secondary structure of the entire apoB molecule is the same in native LDL and HL-LDL. The triglyceride content of LDL reciprocally affected its binding to a monoclonal antibody which recognizes epitopes around the LDL receptor binding domain of apoB. The above evidence indicates that modulation of the core triglyceride and possibly also surface phospholipid content of LDL can alter the conformation of apoB on the surface of the particle, thereby influencing the interaction with cell surface LDL receptors.

Apolipoprotein B-100↗