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PubMed1997

Intraduodenal free fatty acids rather than triglycerides are responsible for the release of CCK in humans.

Exocrine pancreas from different species behaves differently in response to the presence of intact or digested nutrients in the duodenum. A failure of cholecystokinin (CCK) release after a meal has been shown among patients with exocrine pancreatic insufficiency. This abnormality could be restored by the administration of pancreatic extracts, suggesting that digested rather than intact nutrients are responsible for the release of CCK and subsequently gallbladder contraction in humans. The aim of this study was to determine the specific role of different lipidic stimuli in humans. Seven male patients (mean age, 52 years) with pancreatic insufficiency secondary to chronic pancreatitis were selected. Pancreatic insufficiency was considered severe in five of them (lipase output, < 1,000 IU/min) and moderate in another two (lipase output, > 1,000 and < 2,300 IU/min). Plasma CCK (by bioassay), gallbladder contraction (by ultrasound), and enzyme output (chymotrypsin) in response to duodenal administration of either oleic acid as free fatty acids or 20% Intralipid as triglycerides were measured in each patient with at least a 48-h interval between each test. In all these patients with pancreatic insufficiency, duodenal perfusion of free fatty acids generated a more pronounced (91 +/- 11 vs. 49 +/- 21 pM) and faster (15 vs. 30 min) (p < 0.05) CCK release than triglycerides. Furthermore, gallbladder contraction was more efficient when free fatty acids instead of triglycerides were administered in the duodenum (86 +/- 5 vs. 69 +/- 4%) at 10 min (p < 0.05) and (73 +/- 8 vs. 51 +/- 5%) at 15 min (p < 0.03). Among patients with measurable residual pancreatic function, enzyme outputs were shown to be higher during free fatty acid than triglyceride perfusion. In humans, free fatty acids rather than triglycerides, when present in the duodenum, stimulate CCK release and gallbladder contraction. In patients with moderate pancreatic insufficiency this phenomenon may increase residual enzymatic secretion. These results allow us to encourage the development of enzymatic preparations as acid-resistant lipases that cause a fast release of free fatty acids in the duodenum.

Adult↗
PubMed2001

Intracellular metabolism of triglyceride-rich lipoproteins.

Over the past 10 years, many advances have been made in our understanding of the intravascular metabolism of triglyceride-rich lipoproteins. It is now known that the complex extracellular interactions of triglyceride-rich lipoprotein-associated apolipoprotein E, lipoprotein lipase and hepatic lipase with heparan sulfate proteoglycans and lipoprotein receptors facilitate the hepatocellular uptake of triglyceride-rich lipoproteins. Recent studies have also revealed that the intracellular fate of internalized triglyceride-rich lipoproteins is highly complex. The dissociation of triglyceride-rich lipoprotein components within intracellular endosomal compartments involves the recycling of apolipoprotein E, whereas the remaining lipid core associated with apolipoprotein B is susceptible to lysosomal degradation. Apolipoprotein E recycling is an important newly discovered feature of lipoprotein metabolism, and will be discussed in the context of its intracellular transport mechanisms and cholesterol efflux. Current concepts concerning its potential relevance with regard to lipoprotein metabolism and atherosclerosis will also be discussed.

Animals↗
PubMed1976

Changes in transepidermal water loss and the composition of epidermal lecithin after applications of pure fatty acid triglycerides to skin of essential fatty acid-deficient rats.

The importance of various unsaturated fatty acid triglycerides to the repair of faulty skin barrier function was studied in essential fatty acid-deficient rats. Following cutaneous application of the pure triglycerides for up to 5 days, the hitherto high rate of transepidermal water loss, characteristic of essential fatty acid deficiency in rats, was reduced by the triglycerides of linoleic and gamma-linolenic acids. Incorporation of the applied fatty acids into the lecithin of the epidermis accompanied these changes in water loss, indicating that cutaneously applied triglycerides may be metabolized by the skin and incorporated into complex lipids. Other fatty acid triglycerides, including alpha-linolenic, dihomo-gamma-linolenic, arachidonic and omega-7-heneicosatrienoic acid, did not lower the rate of transepidermal water loss, although all were incorporated into epidermal structural lipids. The non-essential oleic acid also had no effect upon the rate of transepidermal water loss. These data suggest that of the two main essential fatty acids that occur in skin, linoleic acid and arachidonic acid, the former specifically plays an important role in regulating barrier function whereas the later may have a separate function, such as serving as a precursor of prostaglandins.

Animals↗
PubMed1978

Hepatic and extrahepatic triglyceride lipase activity in uraemic patients on chronic haemodialysis.

In eleven patients with chronic renal insufficiency treated by intermittent haemodialysis and in ten normal subjects, hepatic and extrahepatic triglyceride lipase activity of post heparin plasma was selectively measured, utilizing the different sensitivity of both enzymes to inhibition by protamine sulphate. In uraemic patients, hepatic triglyceride lipase activity was significantly decreased and extrahepatic triglyceride lipase activity was normal when compared with the control group. The uraemic subjects showed a moderate hypetriglyceridaemia; their serum cholesterol level, however, was normal. The high triglyceride concentration was due to an increase of very low density lipoproteins and low density lipoproteins of the density between 1.006 and 1.019 g/ml (LDL1). The concentration of low density lipoproteins of the density between 1.019 and 1.063 g/ml (LDL2) was decreased. LDL2 were relatively rich in triglycerides when compared with LDL2 from the control group.

Adult↗
PubMed1985

Vitamin D3 uptake by the isolated perfused rat liver from lipoprotein fractions is separate from cholesterol and triglyceride uptake.

Using the isolated perfused rat liver we examined the uptake of [14C] or [3H] vitamin D3 and [14C] triglycerides or [3H] cholesterol by the liver of normal rats, from different lipoprotein fractions, as measured by disappearance from the perfusate. When incorporated into chylomicrons only 43% of the vitamin D3 remained in the perfusate at 60 min (i.e. 57% uptake) as compared to 68% of the triglycerides (i.e. 32% uptake). When added on very low density lipoproteins (VLDL) at 60 min 37 +/- 3% (n = 6) of the vitamin D3, 38 +/- 2% of the cholesterol (n = 3) (P NS), and 83 +/- 4% of the triglycerides (n = 3) remained in the perfusate (P less than 0.0005 for cholesterol:triglycerides and vitamin D3:triglycerides). For high density lipoprotein fraction (HDL) isolated perfused livers were studied with and without albumin present in the perfusate. Without albumin 19 +/- 8% (n = 3) of the vitamin D3 and 43 +/- 8% (n = 3) of the cholesterol remained in the perfusate at 60 min. The results with albumin present were 40 +/- 1% (n = 5) of the vitamin D3 and 63 +/- 4% (n = 5) of the cholesterol at 60 min (P less than 0.0005). The cholesterol:cholesterol ester ratio of the VLDL fraction was 8.8:1 and of the HDL fraction 1:1.4. There was no metabolism of vitamin D3 during the 1 h perfusion. These results suggest that vitamin D3 is in equilibrium with the lipoprotein surface, and the hepatic uptake of vitamin D is a surface phenomenon independent of lipoprotein metabolism.

Animals↗
PubMed1992

Determinants of fasting plasma triglyceride levels: metabolism of hepatic and intestinal lipoproteins.

The contribution of the kinetics of exogeneous and endogenous lipoproteins in determining the level of triglyceride in fasting plasma was assessed in a group of 19 normolipidaemic and hypertriglyceridaemic subjects. From data derived during a 9-h infusion of [15N]-glycine, we have assessed very low density lipoprotein apolipoprotein B production, and from data analysed by kinetic modelling obtained following ingestion of retinol and triolein, we have assessed chylomicron and chylomicron remnant clearance in a group of 19 normolipidaemic and hypertriglyceridaemic subjects. A strong positive correlation was observed between the fasting plasma triglyceride level and the reciprocal of the apolipoprotein B fractional synthetic rate (r = 0.83, P less than 0.01). A positive correlation was also found with the rate of clearance of chylomicron remnants (Sf 20-400; r = 0.87, P less than 0.01) and of chylomicrons (Sf greater than 400; r = 0.69, P less than 0.01). No correlation was found between the fasting plasma triglyceride level and either of the plasma post-heparin lipolytic activities. Multivariate analysis revealed that 95% of the variance in triglyceride levels could be explained by the apolipoprotein B fractional synthetic rate and the chylomicron remnant clearance rate. The strong correlation between chylomicron remnant clearance, a measure of exogenous lipid metabolism, and fasting (hence, endogenous) plasma triglyceride levels suggests that remnants of chylomicrons and very low density lipoproteins share some common components of the removal process.

Adult↗
PubMed1992

Plasma triglyceride and low density lipoprotein metabolism.

This study examines the relationship between plasma triglyceride and low density lipoprotein (LDL) levels by measuring the turnover of the native and 1,2 cyclohexanedione-treated lipoprotein in 25 healthy adults. Plasma triglyceride showed a strong positive correlation with circulating LDL apoprotein (apo LDL) mass. In order to achieve a satisfactory fit to the kinetic data it was necessary to postulate the existence of two plasma apo LDL pools (A and B). When subjects were grouped in quintiles on the basis of circulating apo LDL mass, pool A predominated in those in the lowest quintile. The fractional catabolic rate (FCR) of apo LDL from this pool was high (FCR = 0.57 +/- 0.06 pools day-1). As plasma triglyceride and apo LDL mass rose, apoprotein accumulated in the more slowly metabolized pool B as a result of an increase in the rate of input of apo LDL into the latter. The fractional clearance rate of protein from this pool remained unchanged at 0.26 +/- 0.04 pools day-1. Synthesis of apo LDL into pool B correlated with plasma triglyceride (r = 0.553, P less than 0.01), suggesting that the protein in this pool was derived from large, triglyceride-rich very low density lipoprotein.

Adult↗
PubMed2006

Elevated fasting triglycerides predict impaired glucose tolerance in adolescents at risk for type 2 diabetes.

OBJECTIVE: The aim of this study was to evaluate whether fasting laboratory values can predict impaired glucose tolerance (IGT) in adolescents who are at risk for developing type 2 diabetes mellitus (T2DM). HYPOTHESIS: Elevated fasting triglycerides, a marker for worsening insulin resistance, predict risk for IGT. DESIGN: Following a fast of at least 9 h, laboratory measures, body mass index (BMI), and demographic information were obtained. The subjects then underwent a 75-g oral glucose challenge with a 2-h postchallenge glucose determination. SUBJECTS: Eighty-four adolescents aged 12-20 yr with at least two risk factors for developing T2DM (obesity, family history of T2DM, or acanthosis nigricans) and with either a fasting insulin level > or =25 microU/mL or a homeostasis model assessment of insulin resistance (HOMA-IR) > or =3.5 were recruited for the study. RESULTS: Ten subjects (12%) had IGT [2-h glucose > or =140 mg/dL (7.77 mmol/L)], and 10 subjects (12%) had impaired fasting glucose [IFG; fasting glucose > or =100 mg/dL (5.55 mmol/L)]. However, only three (30%) subjects with IGT had IFG, though all subjects with IGT had a fasting triglyceride level > or =150 mg/dL (1.70 mmol/L). Of those subjects with elevated triglycerides, 29% had IGT. As a screening test to predict risk for IGT, elevated triglycerides >150 mg/dL had a sensitivity of 100% and a specificity of 68%. The positive predictive value was 29%, and the negative predictive value was 100%. CONCLUSIONS: Screening with fasting glucose alone would have missed 70% of subjects with IGT in this population of insulin-resistant adolescents. However, a fasting triglyceride level > or =150 mg/dL was strongly associated with IGT and may help to identify at-risk adolescents who should undergo formal glucose tolerance testing.

Adolescent↗
PubMedDate not supplied

Stimulation of pyloric contractions by intraduodenal triglyceride is persistent and sensitive to atropine.

Intraduodenal lipid infusion stimulates phasic and tonic pyloric contractions and suppresses antral contractions. This study determined: (i) whether this response is sustained over 90 min; and (ii) the role of muscarinic mediation of this response. Antropyloroduodenal motility was recorded in 17 healthy volunteers with a sleeve/sidehole manometric assembly. Subjects received either a 90 min intraduodenal infusion of saline or triglyceride (20% Intralipid) at a rate of 1 mL/min; 30 min after the start of this infusion, the eight subjects who received triglyceride were given intravenous atropine 15 micrograms/kg over 30 s, followed by a maintenance infusion of 4 micrograms/kg/h until the study was completed. Intraduodenal triglyceride infusion stimulated isolated pyloric pressure waves consistently, producing a median rate of 2.4 per min after 30 min of triglyceride infusion, compared with a median rate of 0 per min pre-infusion. In intravenous saline studies, there was a reduction (P < 0.05) in the median rate of isolated pyloric pressure waves to 1.3 per min at 90 min, when compared with pyloric pressure waves at 30 min. Atropine reduced isolated pyloric pressure waves to a median rate of 0 per min, significantly different from preatropine (P < 0.01) and from intravenous saline studies (P < 0.0001). These results indicate that the phasic pyloric response to intraduodenal lipid persists during 90 min stimulation, albeit with significant attenuation. In humans, muscarinic cholinergic blockade prevents the occurrence of triglyceride stimulated localized pyloric contractions.

Adult↗
PubMed1987

Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men.

Men with regular physical training habits voluntarily increased their dietary fat intake from 43 to 54% of energy (E%) for four weeks. This was followed by a low-fat (29 E%), high-carbohydrate diet for another four weeks. During the high-fat diet period, the muscle lipoprotein lipase activity (LPLA) increased from 59 +/- 8 to 106 +/- 12 mU/g (mean +/- SE) (P less than 0.05). After the high-carbohydrate diet, LPLA was 57 +/- 16 mU/g, and unchanged relative to the pre-trial value. The triglyceride content in m. vastus lateralis increased from 30 +/- 4 to 47 +/- 9 mmol/kg d.w. (P less than 0.05; mean +/- SE) following the high-fat diet and to 41 +/- 8 following the high-carbohydrate diet. Neither of the diets affected the serum triglyceride and insulin concentrations, nor glucose, glycerol, beta-hydroxybutyrate, citrate and lactate levels in the blood. Nor did they alter enzyme activities in muscle used as markers for the oxidative (citrate synthase, beta-hydroxy-acyl CoA dehydrogenase) and glycolytic (glyceraldehyde phosphate dehydrogenase, lactate dehydrogenase) capacity. It is concluded that one month's adaptation to a high-fat diet results in increased muscle-LPL activity indicating a higher capacity for uptake of fatty acids from circulating serum triglycerides into the muscle cell in association with a greater capacity for triglyceride storage in the muscle. Under these conditions serum triglycerides were not decreased despite the increased muscle LPLA, and serum insulin variations could not explain the change in muscle LPLA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1977

Concentrations of triglycerides, free fatty acids and glycerol in cord blood of newborn infants with a birth weight of less than or equal to 2700 grams.

Concentrations of triglycerides, free fatty acids (FFA) and glycerol were measured in umbilical venous blood from 99 infants with a birth weight of between 1100-2700 g and a gestational age of 27-41 weeks. Thirty infants were small for gestational age (SGA), 58 were appropriate (AGA) and 11 were of uncertain gestational age. In AGA infants with a gestational age of less than or equal to 35 weeks. FFA values were lower than in those with a gestational age of less than 35 weeks; otherwise concentrations of triglycerides, FFA and glycerol were independent of birth weight and gestational age in AGA infants. In SGA infants, higher FFA values were found compared with both AGA and term infants of normal birth weight. Triglyceride values were higher in SGA than in AGA infants. In SGA infants, a significant positive correlation was found between gestational age and concentrations of both FFA and triglycerides. No differences in FFA, glycerol and triglyceride concentrations were seen between asphyxiated and non-asphyxiated AGA infants.

Asphyxia Neonatorum↗
PubMed1996

The role of medium-chain triglycerides in exercise.

Studies investigating fat as a fuel for exercise have found that increasing free fatty acids during exercise tends to spare muscle glycogen due to increased utilization of free fatty acids for energy, which in turn can enhance the capacity for endurance exercise. Medium-chain triglycerides do not delay gastric emptying or absorption. They are broken down by lipase in the stomach and duodenum to glycerol and medium-chain fatty acids (MCFA). Since MCFAs are metabolized as quickly as glucose, it has been speculated that they might provide an alternative carbon source for the muscle during prolonged exercise. While the majority of studies investigating the role of medium-chain triglycerides and exercise have found no sparing effect of muscle glycogen after consumption of medium-chain triglycerides, two recent studies have presented conflicting results. This review will investigate the speculated role of medium-chain triglycerides as an alternative fuel source for exercising muscles and will discuss the possibility that medium-chain triglycerides preserve muscle glycogen during exercise.

Animals↗
PubMed2004

Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase.

Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.

3T3-L1 Cells↗
PubMed1992

Plasma triglyceride and high density lipoprotein cholesterol as predictors of ischaemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies.

OBJECTIVE: To assess the roles of plasma triglyceride and high density lipoprotein (HDL) cholesterol concentrations in predicting ischaemic heart disease. DESIGN: Two prospective cohort studies with common core protocols. SETTING AND PARTICIPANTS: Both cohorts are 100% samples of middle aged men. In Caerphilly the 2512 men were living within a defined area. In Speedwell the 2348 men were registered with local general practitioners. MAIN OUTCOME MEASURES: Fasting blood samples were taken at initial examination and plasma lipid concentrations were measured. Major ischaemic heart disease events were assessed from hospital notes, death certificates, and electrocardiograms. RESULTS: At first follow up, after an average of 5.1 years in Caerphilly and 3.2 years in Speedwell, 251 major ischaemic heart disease events had occurred. Men with triglyceride concentrations in the top 20% of the distribution had a relative odds value for ischaemic heart disease of 2.3 (95% confidence interval (95% CI) 1.3 to 4.1) compared with men in the bottom 20%, after adjusting for both plasma total and HDL cholesterol, and non-lipid risk factors. Men in the lowest 20% of the distribution of HDL cholesterol concentration had a relative odds value of 1.7 (95% CI 1.0 to 2.8) compared with the top 20%, after adjustment was made for total cholesterol and triglyceride concentrations, and non-lipid risk factors. These relations were not caused by beta blockers, which were being taken by 5% of the men. CONCLUSIONS: Plasma triglyceride concentration predicts major ischaemic events after allowance is made for total and HDL cholesterol concentrations and other risk factors. In these populations, triglyceride is a more important predictor than total cholesterol concentration.

Adrenergic beta-Antagonists↗
PubMed1983

Effect of triglycerides on the production of lipids and lipase by Mucor hiemalis.

The effect of triglycerides on the growth of Mucor hiemalis and the production of lipase and mycelial lipids was studied. Addition of 1% triglycerides to the fermentation medium was best for the mycelial as well as the broth lipase production. The added triglycerides seemed to be utilized through the formation of free fatty acids, and towards the end of the growth phase most of the triglycerides and their hydrolysis products were utilized. The mycelial lipase activity was maximum (66 U/g dry mycelium) at the end of the growth phase, while the maximal broth lipase activity (204 U/100 mL) was achieved after the cell lysis had started. The lipids produced per gram mycelia were high initially (260 mg/g dry weight at 48 h), reducing gradually later. With increase in growth the maximum mycelial lipids per 100 mL of culture medium was obtained after 96 h (176 mg/100 mL). The various fractions detected in the mycelial lipid extracts were sterol esters, triglycerides, free fatty acids, diglycerides, sterols, monoglycerides, phosphatidyl ethanolamine, phosphatidyl choline, and small amounts of an unknown polar lipid at all the stages of fermentation studied. Proportion between total neutral and total polar lipids remained nearly constant throughout fermentation.

Dose-Response Relationship, Drug↗
PubMed1979

An approach to measuring the in vivo transformation of glycerol to a very low density lipoprotein triglyceride.

This paper describes a new method which permits measurement of the steady-state rate of transformation of serum glycerol to a very low density lipoprotein (VLDL) triglyceride in vivo in dogs. Although the turnover of glycerol and the turnover of VLDL triglyceride glycerol have both been previously measured, the rate of transformation of the former into the latter has not. While there is considerable dog-to-dog variation in the absolute turnover and transformation rates, the relationship between the various rates is quite constant. Thus, 13% of the serum glycerol which normal fasting dogs utilize is converted to VLDL triglyceride. The remaining 87% is converted to other products. Also, 28% of VLDL triglyceride glycerol in these dogs is derived from serum glycerol. The balance, 72%, is derived from other sources. The procedure described here can be used to quantitate the contribution of glycerol to VLDL in a number of conditions in which glycerol and (or) VLDL triglyceride metabolism is altered, thereby providing another way to gain insight into the metabolism of VLDL. Even more generally, the principles developed here can be applied to estimate the transformation of other precursors to other products in vivo.

Animals↗
PubMed1999

Kinetics of dodecanedioic acid triglyceride in rats.

The kinetics of the triglyceride of dodecanedioic acid (TGDA) has been investigated in 30 male Wistar rats after a rapid intravenous bolus injection. TGDA and its product of hydrolysis, nonesterified dodecanedioic acid (NEDA), were measured in plasma samples taken at different times using an improved high-performance liquid chromatographic method. The 24-h urinary excretion of TGDA was 1.54 +/- 0.37 micromol, corresponding to approximately 0.67% of the administered amount. Several kinetics models were considered, including central and peripheral compartments for the triglyceride and the free forms and expressing transports between compartments with combinations of linear, carrier-limited, or time-varying mechanisms. The parameter estimates of the kinetics of TGDA and of NEDA were finally obtained using a three-compartment model in which the transfer of TGDA to NEDA was assumed to be linear, through a peripheral compartment, and the tissue uptake of NEDA was assumed to be carrier limited. TGDA had a large volume of distribution ( approximately 0.5 l/kg body wt) with a fast disappearance rate from plasma (0.42 min-1), whereas NEDA had a very small volume of distribution ( approximately 0.04 l/kg body wt) and a tissue uptake with maximal transport rate of 0.636 mM/min. In conclusion, this first study on the triglyceride form of dodecanedioic acid indicates that it is rapidly hydrolyzed and that both triglyceride and nonesterified forms are excreted in the urine to a very low extent. The tissue uptake rate of NEDA is consistent with the possibility of achieving substantial energy delivery, should it be added to parenteral nutrition formulations. Furthermore, the amount of sodium administered with the triglyceride form is one-half of that necessary with the free diacid.

Animals↗
PubMed2000

Glucose-stimulated insulin secretion suppresses hepatic triglyceride-rich lipoprotein and apoB production.

The current study assessed in vivo the effect of insulin on triglyceride-rich lipoprotein (TRL) production by rat liver. Hepatic triglyceride and apolipoprotein B (apoB) production were measured in anesthetized, fasted rats injected intravenously with Triton WR-1339 (400 mg/kg). After intravascular catabolism was blocked by detergent treatment, glucose (500 mg/kg) was injected to elicit insulin secretion, and serum triglyceride and apoB accumulation were monitored over the next 3 h. In glucose-injected rats, triglyceride secretion averaged 22.5 +/- 2.1 microg.ml(-1).min(-1), which was significantly less by 30% than that observed in saline-injected rats, which averaged 32.1 +/- 1.4 microg.ml(-1).min(-1). ApoB secretion was also significantly reduced by 66% in glucose-injected rats. ApoB immunoblotting indicated that both B100 and B48 production were significantly reduced after glucose injection. Results support the conclusion that insulin acts in vivo to suppress hepatic very low density lipoprotein (VLDL) triglyceride and apoB secretion and strengthen the concept of a regulatory role for insulin in VLDL metabolism postprandially.

Animals↗