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PubMed1982

An abnormal triglyceride-rich lipoprotein containing excess sialylated apolipoprotein C-III.

An abnormal triglyceride-rich lipoprotein has been isolated from some patients with chronic renal failure or severe hypertriglyceridemia. The abnormal lipoprotein was characterized by an increased content of apolipoprotein (apo) C-III-2 (57.5% of total apo C-III peptides compared with 35.5% for controls, P less than 0.001) as characterized by isoelectric focusing and scanning densitometry. As determined by a substrate competition assay, the abnormal lipoprotein was a less efficient substrate for purified bovine milk lipoprotein lipase than control lipoproteins. Neuraminidase digestion of abnormal or control lipoprotein resulted in a reduction of the apo C-III-2 band with a corresponding increase in the region of apo C-III-0, which suggests that the increased content of apo C-III-2 in the abnormal is due to excessive sialylation of the C-III peptide. Limited incubation of the abnormal lipoproteins with neuraminidase caused a partial loss of sialic acid and resulted in a triglyceride-rich lipoprotein with a normal C-III-2:C-III-1 ratio. This preparation displayed normal substrate interaction with lipoprotein lipase. Three severely hypertriglyceridemic patients with the abnormal lipoprotein showed a marked reduction in serum triglyceride concentration, which is associated with a reversion to a normal C-peptide profile after dietary therapy. The results suggest that the extent of sialylation of the apo C-III peptide carried on triglyceride-rich lipoproteins may be critical for their interaction with lipoprotein lipase.

Apolipoproteins↗

PubMed2006

Enhancing energy and glucose metabolism by disrupting triglyceride synthesis: Lessons from mice lacking DGAT1.

Although the ability to make triglycerides is essential for normal physiology, excess accumulation of triglycerides results in obesity and is associated with insulin resistance. Inhibition of triglyceride synthesis, therefore, may represent a feasible strategy for the treatment of obesity and type 2 diabetes. Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin sensitivity and are protected against diet-induced obesity and glucose intolerance. These metabolic effects of DGAT1 deficiency result in part from the altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes.

Journal Article↗

PubMed1990

The release of hepatic triglyceride lipase from rat monolayered hepatocytes in primary culture.

The release of hepatic triglyceride lipase from cultured rat hepatocytes and its hormonal regulation were studied. The activity of lipase released into the medium in the presence of heparin was increasing for 24 hours on the 2nd day of culture. The activity in the absence of heparin was only 10% of that in the presence of heparin. When hepatocytes were cultured with anti-hepatic triglyceride lipase IgG, the lipase activity was suppressed by 92%. The results suggest that the enzyme released into the culture medium is identical to hepatic triglyceride lipase which can be released only in the presence of heparin, the mode of release being similar to that of lipoprotein lipase from adipocytes. The addition of colchicine and monensin to the medium resulted in the inhibition of lipase secretion by 20% and 61%, respectively. Insulin enhanced lipase activity only 20%, whereas dexamethasone suppressed the activity by 44%. These data indicated that hepatic triglyceride lipase is secreted and released from hepatocytes in the presence of heparin and its secretion is regulated by hormones.

Animals↗

PubMed1998

[The behaviour of plasma triglycerides and cholesterol in HIV positive haemophiliacs]

Hypertriglyceridemia has frequently been found both in subjects with AIDS and in asymptomatic HIV-positive ones. In order to evaluate the importance of hyperlipemia as an index of the clinical evolution of HIV infection, the levels of triglycerides, total cholesterol and CD4 lymphocytes were determined over a period of 2 years in 8 haemophiliacs with AIDS, 13 asymptomatic HIV-positive and 45 HIV-negative haemophiliacs attending the Operative Unit of Coagulation Disorders of the University of Pisa. The mean concentration of triglycerides and incidence of hypertriglyceridemia were significantly higher in haemophiliacs with AIDS, compared with HIV-negative subjects (p<0.0001), while the triglycerides values of asymptomatic HIV-positives fell between those of the other groups. Cholesterol levels were lower in HIV-positive haemophiliacs and in those with AIDS compared with HIV-negatives. No correlation was found between triglyceride levels and those of CD4 lymphocytes.

Journal Article↗

PubMed1990

[Isolation and properties of triglyceride lipase from the rabbit liver].

Using affinity chromatography on heparin-Sepharose 4B, triglyceride lipase was isolated from rabbit liver tissue and purified. The specific activity of the enzyme isolated from the usual homogenate was equal to (3.8 +/- 1.2) x 10(3) mumol/hour/mg protein. After treatment of liver tissue homogenates with liquid nitrogen the enzyme activity increased severalfold as compared to the enzyme isolated from the usual homogenate. The dependences of the triglyceride lipase activity on the concentrations of the protein (enzyme), substrate (triglyceride), albumin (fatty acid acceptor) and pH were studied. The isolated form of liver triglyceride lipase was found to have two pH optima at 6.5 and 8.5.

Albumins↗

PubMed1989

Heparin-modulated binding of pancreatic lipase and uptake of hydrolyzed triglycerides in the intestine.

Utilizing small intestine membranes that contain heparin (50 micrograms/mg protein), binding of triglyceride lipase (homogeneous 52 kDa, specific activity, 70 nmol/mg.h) to membranes was shown to be concentration dependent and saturable, and it was characterized by a single dissociation constant (KD = 86 +/- 16 nM) with a maximal binding capacity of 54 +/- 8 pmol/mg of vesicle protein. Specific binding was decreased in a concentration-dependent manner by the addition of exogenous heparin, and binding was virtually eliminated (less than 6% control values) by pretreatment of membranes with bacterial heparinase. Cultured intestinal epithelial cells (CaCo-2), shown to possess membrane-associated heparin, also bound pancreatic triglyceride lipase in a specific and saturable manner, with KD = 77 +/- 12 nM and Bmax = 13.7 +/- 6 pmol/10(6) cells. Soluble heparin not only decreased binding, but it also diminished the enzyme-mediated cellular uptake of [14C]oleate from [14C]triolein by over 75%. Therefore, intestinal heparin, a component of the brush border membrane, localizes pancreatic triglyceride lipase in a receptor-like manner to the plasma membrane to promote the subsequent absorption of fatty acids derived from hydrolyzed triglycerides.

Adenocarcinoma↗

PubMed1989

Effects of weight loss and weight maintenance on the serum lipids, lipoprotein lipase and hepatic triglyceride lipase activities in obese rats.

The effects of obesity, weight loss and weight maintenance on the serum lipid levels and lipoprotein lipase and hepatic triglyceride lipase were investigated in rats. Obesity induced by high-fat (HF) feeding was associated with decreased serum triglyceride levels (HF: 70.3 +/- 8.2, control (CON): 140.0 +/- 26.9 mg/dl, P less than 0.05), increased lipoprotein lipase (LPL, HF: 593.2 +/- 10.6 vs CON: 280 +/- 19.5 nmol FFA/min per mg tissue, P less than 0.05) and suppressed hepatic triglyceride lipase activities (HTGL, HF: 14.2 +/- 0.5 vs CON: 18.0 +/- 0.4 nmol FFA/min per mg tissue, P less than 0.01). After a weight loss to the level of control rats, weight maintenance was achieved either by high-protein (HP) or chow feedings (CH). Both high-protein (HFHP) and chow (HFHC) groups had similar weights but only high-protein feeding restored the normal body compositions. Both groups of rats had higher total (TC, HFHP: 146 +/- 10.7; HFCH: 104.8 +/- 5.1 mg/dl), and high density lipoprotein cholesterol levels (HDL-C, HFHP: 100.8 +/- 15.6; HFCH: 75.5 +/- 5.5 mg/dl) and lower lipoprotein lipase (HFHP: 238.2 +/- 15.8, HFCH: 354.8 +/- 34.9 nmol FFA/min per mg tissue) and hepatic triglyceride activities (HFHP: 16.3 +/- 1.1; HFCH: 14.5 +/- 0.6 nmol FFA/min per mg tissue) than control rats (TC: 70.1 +/- 4.7 mg/dl; HDL-C: 14.2 +/- 4.3 mg/dl; LPL: 742.4 +/- 82.3 nmol FFA/min per mg tissue; HTGL: 20.5 +/- 1.0 nmol FFA/min per mg tissue, P less than 0.05 to 0.005) or the rats who regained weight by resuming high-fat feeding (TC: 59.5 +/- 6.7 mg/dl; HDL-C: 10.2 +/- 6.7 mg/dl; LPL: 1284.3 +/- 90 nmol FFA/min per mg tissue; HTGL: 22.2 +/- 1.9 nmol FFA/min per mg tissue, P less than 0.05 to 0.005). The high protein-group had significantly higher total and high-density-lipoprotein cholesterol levels than the chow fed animals despite comparable body weights in both groups. The findings of this study suggest that weight maintenance induced by high protein feeding is more successful in restoring the normal body composition. However, high protein feeding is also associated with high serum cholesterol levels. The clinical applications of these findings need to be evaluated further.

Animals↗

PubMed1986

Univariate and bivariate analyses of cholesterol and triglyceride levels in pedigrees.

A multivariate normal model for pedigree analysis is applied to fasting total serum cholesterol and total serum triglyceride measurements on 771 individuals in 95 pedigrees from Rochester, MN. Univariate and bivariate analyses are carried out to determine to what extent the aggregation and coaggregation in families of these two traits may be attributed to shared genetic and environmental factors. Pedigrees were ascertained through a sample of schoolchildren enriched for those with serum cholesterol levels in the highest and lowest deciles of their age- and sex-specific distributions. Ascertainment is corrected for by conditioning the likelihood on the trait values of the probands. Univariate results confirm the findings of previous studies indicating that familial aggregation of serum cholesterol and triglyceride levels is due both to shared genes and to shared environmental factors. Results of the bivariate analyses suggest that the coaggregation of cholesterol and triglyceride levels in these families is strongly influenced by both shared genes (pleiotropy) and shared environmental factors. These findings are consistent with our understanding of lipid metabolism and of specific environmental factors known to influence both traits.

Adolescent↗

PubMed2005

Traditional Chinese Medicine improves dysfunction of peroxisome proliferator-activated receptor alpha and microsomal triglyceride transfer protein on abnormalities in lipid metabolism in ethanol-fed rats.

We report the effects of Traditional Chinese Medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida, Alisma oriental, Salvia miltiorrhiza and Pueraria lobata. The rats were separated randomly into five groups; the CD group (n=10), which was fed a control diet for 10 weeks, the ED group (n=10), which was fed an isocaloric liquid diet containing ethanol for 10 weeks and given daily oral doses of TCM (0.222 g/kg/day; TCM222, 0.667 g/kg/day; TCM667, and 2.000 g/kg/day; TCM2000, n=10, respectively) over the last four weeks of the study. The ED group developed fatty livers, as determined by their lipid profiles and liver histological findings. Compared with the control group, liver/body weight, plasma triglyceride (TG) and total cholesterol (TC), liver TG and TC, plasma alanine aminotransferase (ALT) and aspartic aminotransferase (AST) significantly increased in the ED group. Also, free fatty acids (FFA) levels increased in both plasma and liver during the administration of ethanol. On the other hand, when rats were administrated with TCM, their liver/body weight, plasma TG, TC and FFA, liver TG, TC and FFA, plasma ALT and AST decreased significantly and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group. Proper function of the peroxisome proliferator-activated receptor alpha (PPARalpha) is essential for the regulation of hepatic fatty acid metabolism. Microsomal triglyceride transfer protein (MTP) is essential for the secretion of triglycerides from the liver. mRNAs for PPARalpha and MTP were reduced in the livers of ethanol-fed rats. TCM restored the mRNA levels of PPARalpha and MTP, and prevented development of fatty livers in ethanol-fed rats. Impairment of PPARalpha and MTP function during ethanol consumption contributes to the development of alcohol-induced fatty liver, which can be overcome by TCM.

Alanine Transaminase↗

PubMed1985

Familial aortic aneurysms: serum concentrations of triglyceride, cholesterol, HDL-cholesterol and (VLDL + LDL)-cholesterol.

Patients with abdominal aortic aneurysms (AAAs) have been compared with healthy controls with respect to the serum concentrations of triglyceride, cholesterol, HDL-cholesterol and (VLDL + LDL)-cholesterol. The concentrations of triglyceride and (VLDL + LDL)-cholesterol in serum were higher in the patients than in the controls, while the concentration of HDL-cholesterol in serum was lower in the patients than in the controls. There was no statistically significant difference in the serum concentration of total cholesterol between the patients and the controls. Twelve patients had first degree relatives (brothers, sisters and/or parents) with AAAs and six patients had second degree relatives (cousins or brothers and sisters of the parents) with AAAs. There was no statistically significant difference between the patients who had first degree relatives with AAAs and the patients without AAAs in the family in the serum concentrations of triglyceride, cholesterol, HDL-cholesterol and (VLDL + LDL)-cholesterol.

Aged↗

PubMed1991

Evaluation of (13C)ethanol incorporation into very-low-density lipoprotein triglycerides using gas chromatography/isotope ratio mass spectrometry coupling.

Gas chromatography/isotope ratio mass spectrometry (GC/IRMS) coupling was used to evaluate (13C)ethanol incorporation into plasmatic very-low-density lipoprotein (VLDL) triglycerides of three healthy human volunteers. After the perfusion of 13C-enriched alcohol, VLDL triglyceride fractions were extracted from plasma samples and prepared for the analysis of (13C)fatty acid methyl esters. The GC/IRMS coupling line, the analytical procedure and the data collection are described. The results show that ethanol itself may be used as a substrate for lipogenesis, though to a small extent: less than 10% of VLDL triglycerides may be derived from this metabolic pathway. Ethanol incorporates predominantly into myristic and palmitic acid. The small amount of sample material required for analysis, which minimizes the amount of isotope-labelled substrate required, makes this technique a valuable tool for metabolic investigations in human subjects.

Carbon Isotopes↗

PubMedDate not supplied

Determinants of postprandial triglyceride and remnant-like lipoproteins in type 2 diabetes.

BACKGROUND: Postprandial changes in remnant-like lipoprotein particles (RLP) contribute to the severity of coronary heart disease in type 2 diabetes. Since the determinants of postprandial response in RLP are not well understood, this study investigated the roles of fasting triglyceride, apolipoprotein (apo) E polymorphism and insulin resistance in a group of overweight/obese Chinese type 2 diabetic subjects. METHODS: Postprandial triglyceride (TG) and RLP-cholesterol (RLP-C) were determined after a mixed meal containing 70-g fat at 2-h intervals for 8 h in 32 normotriglyceridemic (NTG) and 31 hypertriglyceridemic (HTG) subjects. RLP-C was measured using an immunoseparation assay and apo E genotypes using polymerase chain reaction and restriction mapping. Insulin resistance was defined as homeostasis model assessment index (HOMA-IR). RESULTS: The HTG subjects had greater postprandial increase in TG and RLP-C than NTG (p < 0.001), but there were no significant differences in HOMA-IR and apo E allele frequencies. Subjects who were non-E3-carriers had the largest postprandial increment in TG and RLP-C. On stepwise linear regression analysis, log(HOMA-IR) was only an independent determinant of fasting TG but not postprandial TG or RLP-C. The major determinants of fasting and postprandial RLP-C were fasting TG and apo E genotype, accounting for 53 and 6% of the variance of fasting RLP-C (p < 0.01) and 31 and 13% of the variance of postprandial RLP-C respectively (p < 0.01). CONCLUSIONS: Insulin resistance is mainly a determinant of fasting triglyceride in Chinese type 2 diabetic subjects, whereas apo E genotype is a better predictor of both fasting and postprandial concentrations of RLP.

Adult↗

PubMed1984

Influence of garlic on serum cholesterol, serum triglycerides, serum total lipids and serum glucose in human subjects.

Human subjects were used for a garlic experiment. The subjects were given a fat-rich diet for 7 days and on the 8th day the fasting blood was analyzed for serum cholesterol, serum triglycerides, serum total lipids and serum glucose. The human subjects were then given a fat-rich diet with 40 g of garlic for 7 days and on the 15th day the fasting blood was analyzed for the above investigations. On a fat-rich diet the serum cholesterol, serum triglycerides and serum total lipids were significantly increased as compared to normally fed diet. When 40 g of garlic was substituted in fat-rich diet for 7 days, the garlic significantly reduced the serum cholesterol and serum triglycerides.

Adult↗

PubMed1991

Effect of fat and retinol loading on serum triglyceride and retinol levels in patients with ulcerative colitis.

Serum copper, zinc, selenium, magnesium, calcium, cholesterol, triglyceride and retinol contents were determined in 11 patients with ulcerative colitis and in 20 healthy volunteers. Lipid and retinol loadings were performed as well. No differences were found in serum copper, zinc, calcium and selenium levels between the groups. Serum magnesium levels were somewhat lower in the patients than in the volunteers. During the period of loading, cholesterol levels did not differ between the two groups at any time. Triglyceride levels except for two persons, were higher in patients. Triglyceride curves showed pathological courses in each case. Retinol concentrations in patients remained below the values observed in volunteers. Data suggest a disturbed utilization of fat and retinol in patients with ulcerative colitis.

Adolescent↗

PubMed1998

Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation.

The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.

Adipose Tissue↗

PubMed1999

Components of total energy expenditure in healthy young women are not affected after 14 days of feeding with medium-versus long-chain triglycerides.

OBJECTIVE: To examine the effect of consumption of medium-chain triglycerides (MCT) vs. long-chain triglycerides (LCT) on total energy expenditure (TEE) and its components in young women during the second week of a 2-week feeding period. RESEARCH METHODS AND PROCEDURES: Twelve healthy lean women (age: 22.7+/-0.7 years, body mass index [BMI]: 21.5+/-0.8 kg/m2) were fed weight maintenance diets containing 15% of energy as protein, 45% as carbohydrate, and 40% as fat, 80% of which was treatment fat, for 2 weeks in a randomized cross-over design separated by a 2-week washout period. Dietary fat was composed of triglycerides containing either 26% medium-chain fatty acids (MCFA) and 74% long-chain fatty acids (LCFA), or 2% MCFA and 98% LCFA. Free-living TEE was measured from day 7 to 14 on each dietary treatment using doubly labeled water (DLW). Basal metabolic rate (BMR) and thermic effect of food (TEF) were measured on days 7 and 14 using respiratory gas exchange analysis (RGE) for 30 minutes and 330 minutes, respectively. Activity-induced energy expenditure (AIEE) was derived as the difference between TEE and the sum of BMR and TEF. RESULTS: The average TEE while consuming the MCT diet (2246+/-98 kcal/day) did not differ from that of the LCT diet (2186+/-138 kcal/day. BMR was significantly higher on the MCT diet on day 7 (1219+/-38 kcal/day vs. 1179+/-42 kcal/day), but not on day 14; there was no effect of diet on TEF. There were no differences in BMR, TEF, or AIEE between diets when expressed as percentages of TEE. On average, BMR, TEF, and AIEE represented 54.6%, 8.2%, and 37.2%, respectively, of TEE. DISCUSSION: Results suggest that between day 7 and day 14 feeding of MCT vs. LCT at these levels, TEE is not affected and that increases seen in energy expenditure following MCT feeding may be of short duration. Thus, compensatory mechanisms may exist which blunt the effect of MCT on energy components over the longer term.

Adult↗

PubMed1993

Functional alterations of human neutrophils by medium-chain triglyceride emulsions: evaluation of phagocytosis, bacterial killing, and oxidative activity.

Medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) emulsions currently used in nutritional therapy were evaluated for their in vitro effect on neutrophil oxidative metabolism, phagocytosis, and bacterial killing activities. Neutrophils from healthy adult male volunteers were assessed after blood incubation with commercially available fat emulsions containing LCT, MCT, or a mixture of 50% MCT and 50% LCT at a final triglyceride concentration of 20 mg/ml. It was observed that MCT-containing emulsions stimulated nitroblue tetrazolium (NBT) dye reduction by neutrophils as determined by a cytochemical NBT test performed directly on whole blood. This effect was dose dependent. However, after lipid removal by cell washing, the MCT-treated neutrophils showed decreased production of hydrogen peroxide (H2O2) and NBT reduction in response to bacterial lipopolysaccharide or phorbol myristate acetate stimuli as well as impaired phagocytosis and killing of Staphylococcus aureus. In contrast, the LCT emulsion did not alter any of the neutrophil functions evaluated. The present data suggest that MCTs elicit the oxidative metabolism of neutrophils, probably by phagocytosis of fat particles and, depending on the lipid concentration, this effect may not be reversible, leading to impairment of the cellular response to subsequent membrane stimuli.

Adolescent↗

PubMed1997

Crystal structure of cutinase covalently inhibited by a triglyceride analogue.

Cutinase from Fusarium solani is a lipolytic enzyme that hydrolyses triglycerides efficiently. All the inhibited forms of lipolytic enzymes described so far are based on the use of small organophosphate and organophosphonate inhibitors, which bear little resemblance to a natural triglyceride substrate. In this article we describe the crystal structure of cutinase covalently inhibited by (R)-1,2-dibutyl-carbamoylglycero-3-O-p-nitrophenylbutyl-phos phonate, a triglyceride analogue mimicking the first tetrahedral intermediate along the reaction pathway. The structure, which has been solved at 2.3 A, reveals that in both the protein molecules of the asymmetric unit the inhibitor is almost completely embedded in the active site crevice. The overall shape of the inhibitor is that of a fork: the two dibutyl-carbamoyl chains point towards the surface of the protein, whereas the butyl chain bound to the phosphorous atom is roughly perpendicular to the sn-1 and sn-2 chains. The sn-3 chain is accommodated in a rather small pocket at the bottom of the active site crevice, thus providing a structural explanation for the preference of cutinase for short acyl chain substrates.

Carboxylic Ester Hydrolases↗