Plasma Hepatic Triglyceride Lipase Activity Research Articles

Upregulation of fatty acid synthesis and the suppression of hepatic triglyceride lipase as a direct cause of hereditary postprandial hypertriglyceridemia in rabbits

Rabbits with hereditary postprandial hypertriglyceridemia exhibit central obesity and are regarded as a reliable model for metabolic syndrome. This study was performed to gain insight into the affected process of lipid metabolism and into the causative genes of the postprandial hypertriglyceridemia rabbits. Eleven genes that play key roles in lipid metabolism were selected, their mRNA levels were assessed by quantitative PCR, and their expressions were compared among postprandial hypertriglyceridemia rabbits using Japanese white rabbits as the control. Two genes appeared to be in causal connection with postprandial hypertriglyceridemia, and these were regarded as likely candidates for the pathogenesis. One was the fatty acid synthase gene, which had an expression constitutively higher in postprandial hypertriglyceridemia rabbits than in Japanese white rabbits during the fasting state and reached quite high levels after feeding. The other was the gene for hepatic triglyceride lipase with an expression that was approximately one order lower than that found in the Japanese white rabbits. The low plasma hepatic triglyceride lipase activities were consistent with the low levels of the transcript in the livers of the postprandial hypertriglyceridemia rabbits. Thus, elevated fatty acid synthesis and defected lipid hydrolysis together would cause the postprandial hypertriglyceridemia in postprandial hypertriglyceridemia rabbits.

Lipoprotein metabolism in postmenopausal and oophorectomized women

To investigate the mechanisms of accumulating cholesterol, and to analyze the metabolism of excess tissue cholesterol in women with low plasma levels of sex steroid hormones. We measured plasma concentrations of cholesterol, triglyceride, apolipoproteins, sex steroid hormones, and lecithin cholesterol acyltransferase activity in 20 premenopausal, ten postmenopausal, and ten bilaterally oophorectomized women. Lipoprotein lipase and hepatic triglyceride lipase activities were measured in postheparin plasma. We compared the three groups and evaluated a correlation between lipid metabolism and sex steroid hormone concentrations. The mean plasma low-density lipoprotein (LDL) cholesterol level, lecithin cholesterol acyltransferase activity, and postheparin plasma lipoprotein lipase activity were higher in the postmenopausal and surgically menopausal groups. The mean plasma high-density lipoprotein (HDL) cholesterol concentration and postheparin plasma hepatic triglyceride lipase activity did not differ significantly among the three groups. The plasma LDL cholesterol level and postheparin plasma lipoprotein lipase activity showed a significantly negative correlation with plasma concentration of estrone (LDL: r = 0.64, P < .001; lipoprotein lipase: r = 0.54, P < .005) and estradiol (LDL: r = 0.65, P < .001; lipoprotein lipase: r = 0.47, P < .01), but not with that of testosterone. There was no significant relationship between postheparin plasma hepatic triglyceride lipase activity and plasma sex steroid hormones. Plasma lecithin cholesterol acyltransferase activity correlated significantly with plasma LDL cholesterol concentration, but not with levels of sex steroid hormones. Because of low endogenous estrogens, enhanced postheparin plasma lipoprotein lipase activity may lead to an elevated plasma LDL cholesterol concentration in postmenopausal and bilaterally oophorectomized women. We demonstrated an accelerated cholesterol esterification in HDL cholesterol that may have been induced by LDL cholesterol accumulation, although the HDL cholesterol concentration remained unchanged.

Loss of abdominal fat and metabolic response to exercise training in obese women

Numerous studies have shown that a high accumulation of abdominal fat is associated with metabolic complications and with an increased risk of coronary heart disease. The present study examined the effects of changes in body fatness and in the level of abdominal fat on metabolic variables in a sample of 13 obese premenopausal women, aged 38.8 +/- 5.3 (SD) yr. Women exercised for 90 min at approximately 55% of maximal aerobic power (VO2 max) four to five times a week for a period of 14 mo. The training program induced a significant increase in VO2 max and a mean reduction in body fat mass of 4.6 kg (P less than 0.01), with no change in fat-free mass. Measurement of adipose tissue areas by computed tomography indicated a greater loss of abdominal fat compared with midthigh adipose tissue (P less than 0.05). The training program also produced significant reductions in the insulinogenic index measured during an oral glucose tolerance test and in plasma cholesterol (Chol), low-density lipoprotein (LDL)-Chol, and apolipoprotein (apo) B levels (P less than 0.05). Training also significantly increased plasma high-density lipoprotein (HDL)-apo A-I and HDL2-Chol levels and decreased plasma HDL3-Chol concentration (P less than 0.05). Whereas no change in postheparin plasma lipoprotein lipase activity was noted, a significant decrease in postheparin plasma hepatic triglyceride lipase activity was observed after training (P less than 0.005). Metabolic responses were not correlated with changes in VO2 max but were significantly correlated with the reduction in body fat mass and/or with the loss of deep abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)

High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered

We examined the influence of aromatization of testosterone on serum high-density lipoprotein cholesterol (HDL-C) and postheparin plasma hepatic triglyceride lipase activity (HTLA) in men. Eighteen healthy lean nonsmokers (ages, 20 to 33) were administered androgens in a weekly total dose of 280 mg for 12 weeks in one of three groups: testosterone enanthate (TE) (280 mg/wk intramuscularly [IM]); TE (280 mg/wk IM) + testolactone (TL) (250 mg orally [PO] four times daily); or methyltestosterone (MeT) (20 mg PO twice daily). Serum testosterone achieved steady state levels by 4 weeks with >40 nmol/L (TE and TE + TL) and <15 nmol/L (MeT) while 17b-estradiol (E2) rose to >250 pmol/L (TE) or remained below 70 pmol/L (TE + TL and MeT). LH fell to less than 5 U/L (TE and TE + TL) but remained unchanged with MeT. By 4 weeks, HDL-C had decreased significantly from 1.20 ± 0.13 to 0.77 ± 0.13 mmol/L (MeT), from 1.18 ± 0.15 to 0.89 ± 0.13 mmol/L (TE + TL), and demonstrated no decrease in the TE group across the time course of the study. These changes were preceded by mean increases in HTLA of 102% (MeT) and 55% (TE + TL) over baseline, and no significant change with TE. The changes in HDL-C and HTLA returned to baseline within 2 weeks of steroid cessation. There were no changes in total cholesterol, triglycerides, or insulin in any group but, in the MeT group, apo AI levels decreased and low-density lipoprotein cholesterol (LDL-C) increased. After 12 weeks of treatment, sex hormone binding globulin (SHBG) levels were decreased to 37% (MeT), 54% (TE + TL), and 73% (TE) of baseline levels; these changes were evident by the second week of treatment and returned to baseline by the second week following treatment cessation. These results suggest that TE has little effect on HTLA but when a corresponding increase in E2 levels is prevented, HTLA increases. MeT, which is not metabolized to E2, produced the most dramatic HTLA increases, even at a dose that did not reduce serum LH; thus, hepatic specific properties of 17-alkylated androgens may further increase the atherogenic potential of this class of androgens.

Lipoprotein, apolipoprotein, and lipolytic enzyme changes following estrogen administration in postmenopausal women.

To test whether estrogen can modulate the cholesterolemic response to an Occidental diet, six healthy postmenopausal women were studied for 84 days while ingesting a solid food diet of constant composition high in cholesterol content (995 mg/d). In the middle of the study, estrogen (17 alpha-ethinyl estradiol, 1 microgram/kg per day) was administered orally. Ingestion of the diet for the initial 28 days did not alter lipoprotein lipid or apolipoprotein (apo) levels. However, with just 4 days of estrogen use there were significant decreases in apoE (-36%), low density lipoprotein cholesterol (-26%), and postheparin plasma hepatic triglyceride lipase activity (HTGL) (-61%), and an increase in high density lipoprotein (HDL) triglyceride (72%). These changes persisted throughout the estrogen use. The percent change in HTGL with 4 days of estrogen correlated inversely with the percent change in HDL triglyceride (rs = -0.94). After 28 days of estrogen there were also significant increases in HDL cholesterol (21%), HDL2 cholesterol (42%), apoA-I (37%), and apoA-II (9%), and a decrease in apoB (-11%). The level of apoE at this juncture correlated inversely with the level of HDL cholesterol (rs = -0.90), and the levels of HTGL and apoA-I correlated with HDL2 cholesterol (rs = -0.89 and rs = 0.89, respectively). Thus, HTGL may play a role in both the early estrogen-related changes in HDL triglyceride and apoE and the late estrogen-related changes in HDL cholesterol, apoA-I, and apoA-II.

Preliminary report: Kinetic studies on the modulation of high-density lipoprotein, apolipoprotein, and subfraction metabolism by sex steroids in a postmenopausal woman

To investigate the effects of estrogens and androgens on the metabolism of high density lipoproteins (HDL) and low density lipoproteins (LDL), a normolipidemic postmenopausal woman was studied under the following conditions: (1) during supplementation with ethinyl estradiol (0.06 mg/d); (2) without sex steroid therapy; and (3) during treatment with stanozolol, an androgenic, anabolic steroid (6 mg/d). During these manipulations HDL and LDL cholesterol levels fluctuated widely but reciprocally: during estrogen supplementation HDL increased while LDL decreased; during stanozolol HDL-C decreased while LDL-C increased. Simultaneous changes in post-heparin plasma hepatic triglyceride lipase activity paralleled those of LDL (and opposed those of HDL), decreasing with estrogen and increasing with stanozolol. During all three phases, autologous 125I-HDL turnover studies disclosed similarities between HDL 2 and apolipoprotein A-I metabolism and between HDL 3 and apolipoprotein A-II metabolism. In the untreated state the residence times of HDL 2 and apo A-I were only half those of HDL 3 and apo A-II. During estrogen treatment HDL 2 and apo A-I, residence times were selectively prolonged, coming to resemble those of HDL 3 and apo A-II, which remained unchanged. By contrast, during stanozolol treatment HDL 3 and apo A-II residence times were selectively reduced, coming to resemble those of HDL 2 and apo A-I, which remained unchanged. Apo A-I levels increased on estrogen and decreased on stanozolol, while apo A-II remained stable. Hence, estrogen increased HDL primarily by retarding the catabolism of the HDL 2 subfraction rich in apo A-I, whereas stanozolol decreased HDL by accelerating the catabolism of HDL 3, relatively rich in apo A-II. These effects may have been mediated via the concomitant sex steroid-induced changes in the activity of hepatic triglyceride lipase, hypothesized to be a central enzyme in the regulation of HDL catabolism.

Lipoprotein metabolism during acute inhibition of hepatic triglyceride lipase in the cynomolgus monkey.

The role of the enzyme hepatic triglyceride lipase was investigated in a primate model, the cynomolgus monkey. Antisera produced against human postheparin hepatic lipase fully inhibited cynomolgus monkey posttheparin plasma hepatic triglyceride lipase activity. Lipoprotein lipase activity was not inhibited by this antisera. Hepatic triglyceride lipase activity in liver biopsies was decreased by 65-90% after intravenous infusion of this antisera into the cynomolgus monkey. After a 3-h infusion of the antisera, analytic ultracentrifugation revealed an increase in mass of very low density lipoproteins (S(f) 20-400). Very low density lipoprotein triglyceride isolated by isopycnic ultracentrifugation increased by 60-300%. Analytic ultracentrifugation revealed an increase in mass of lipoproteins with flotation greater than S(f) 9 (n = 4). The total mass of intermediate density lipoproteins (S(f) 12-20) approximately doubled during the 3 h of in vivo enzyme inhibition. While more rapidly floating low density lipoproteins (S(f) 9-12) increased, the total mass of low density lipoproteins decreased after infusion of the antibodies. The changes in high density lipoproteins did not differ from those in control experiments. In order to determine whether the increases of plasma concentrations of very low density lipoproteins were due to an increase in the rate of synthesis or a decrease in the rate of clearance of these particles, the metabolism of radiolabeled homologous very low density lipoproteins was studied during intravenous infusion of immunoglobulin G prepared from the antisera against hepatic triglyceride lipase (n = 3) or preimmune goat sera (n = 3). Studies performed in the same animals during saline infusion were used as controls for each immunoglobulin infusion. There was a twofold increase in the apparent half-life of the very low density lipoprotein apolipoprotein-B tracer in animals receiving the antibody, consistent with a decreased catabolism of very low density lipoproteins. Concomitantly, the rise in low density lipoprotein apoprotein-B specific activity was markedly delayed. None of these changes were observed during infusion of preimmune immunoglobulin G.Hepatic triglyceride lipase participates with lipoprotein lipase in the hydrolysis of the lipid in very low density lipoproteins, intermediate density lipoproteins, and the larger low density lipoproteins (S(f) 9-12). Thus, hepatic triglyceride lipase appears to function in a parallel role with lipoprotein lipase in the conversion of very low density and intermediate density lipoproteins to low density lipoproteins (S(f) 0-9).

Roles of lipoprotein lipase and hepatic triglyceride lipase in the catabolism in vivo of triglyceride-rich lipoproteins.

To define the roles, in vivo, of hepatic triglyceride lipase and lipoprotein lipase in the catabolism of triglyceride-rich lipoproteins, we investigated the relationship between the activities of the above enzymes in postheparin plasma and the fractional removal rates of very low density lipoproteins (VLDL) and VLDL remnant particles. In 22 patients, the fractional removal rates of VLDL and VLDL-remnant particles were determined from analyses of the disappearance of radioiodinated Sf 60-400 and Sf 12-60 lipoprotein B apoprotein. The maximal activities of hepatic triglyceride lipase and lipoprotein lipase were determined in plasma samples drawn 2-60 minutes after heparin injection (60 U/kg). A positive correlation was observed between the fractional removal rate of VLDL and postheparin plasma lipoprotein lipase activity (r = 0.65). When all 22 patients were considered together, no relationship was demonstrable between remnant fractional removal and postheparin plasma lipoprotein lipase activity. However, humans may be subdivided with respect to the way in which they catabolize remnants. In some, all remnant may be catabolized to form LDL. In others, some of the remnant may also be directly removed from the circulation. Those subjects in whom previous studies indicate that all remnant is converted to LDL demonstrated a positive correlation between remnant fractional removal rate and postheparin plasma lipoprotein lipase activity (n = 8, r - 0.83). No correlations between postheparin plasma hepatic triglyceride lipase activity and any of the fractional removal rates were found. These data are consistent with the following: 1) lipoprotein lipase plays a key regulatory role in the catabolism of triglyceride-rich lipoproteins; 2) this role applies only to those catabolic involving the formation of particles of higher density VLDL remnants and low density lipoprotein; and 3) hepatic triglyceride lipase plays no rate-limiting role in the catabolism of VLDL or VLDL-remnant particles.

Effect of clofibrate on postheparin plasma triglyceride lipase activities in patients with hypertriglyceridemia

The lipoprotein lipase (LPL) and hepatic triglyceride lipase (HL) activities of post-heparin plasma were determined by a specific immunochemical method in 17 patients with primary hyperlipoproteinemia before and during treatment with clofibrate. The drug caused a significant reduction of serum cholesterol (11%) and triglyceride (45%) levels. Postheparin plasma LPL activity rose in all subjects, the average change being 46% ( P < 0.001). The increase of LPL was positively correlated to the pretreatment LPL activity. There was no correlation between the serum triglyceride concentration and post-heparin LPL activity either before or during clofibrate administration. On the other hand, in the clofibrate responders there was a weak correlation between the relative changes of triglyceride concentration and LPL activity ( r = 0.43, p < 0.05). During clofibrate treatment the LPL activity of the hypertriglyceridemic patients was significantly higher than the corresponding value of untreated healthy normoglyceridemic subjects of similar age. The post-heparin plasma HL activity was not influenced by clofibrate.