Increase of adipose tissue lipoprotein lipase activity with weight loss.

Obese subjects have elevated adipose tissue lipoprotein lipase activity per fat cell when compared with lean control subjects. This enzyme, which is rate limiting for the uptake and storage of lipoprotein triglyceride in adipose tissue, has been shown to be further elevated in a group of previously obese subjects who had been weight stable at a reduced weight for 4-28 mo. In the present prospective study of eight obese subjects, adipose tissue lipoprotein lipase activity was demonstrated to increase after weight stabilization at a reduced weight (0.33 mU/10(6) cells). In three subjects who lost weight and subsequently regained their lost weight, the enzyme activity increased after weight loss and then returned toward the original basal level with weight gain. One subject who maintained his weight loss for 10 mo. continued to have an elevated level of enzyme activity. Because adipose tissue lipoprotein lipase activity does not "normalize" after weight loss, we hypothesize that this enzyme may play a counterregulatory role in resisting deviation from a "set point" for fat mass or fat cell size and thereby predispose to reattainment of the original obese state.     

Effects of apolipoproteins on lipoprotein lipase activity of human adipose tissue.

The effect of apolipoproteins isolated from HDL and VLDL on the activity of lipoprotein lipase (LPL) of adipose tissue was studied. The CII apoprotein was found to activate LPL. This activation was strongly inhibited by CI, AI (apo-Lp-Gln I), and the arginine-rich apoprotein, whereas AII and CIII exhibited a considerably lower inhibitor effect.     

Weight reduction increases adipose tissue lipoprotein lipase responsiveness in obese women.

Lipoprotein lipase was measured in gluteal adipose tissue from nine obese (90.6 +/- 2.7 kg) women fasting and after the intravenous infusion of insulin and glucose before, immediately after, and 3 mo subsequent to a 14.0 +/- 1.8% (mean +/- SEM) weight reduction. Fasting adipose tissue lipoprotein lipase activity (ATLPL) decreased from 5.3 to 2.3 nEq FFA/10(6) cells per min (P less than 0.02) immediately after weight reduction, yet after weight maintenance, higher levels were again found (6.1 nEq FFA/10(6) cells per min). Although responsiveness of ATLPL to 40 mU/m2 per min of insulin infusion over 6 h was absent before weight loss, increases were seen immediately after weight loss (delta 0.8, P = 0.05) and more so (delta 7.7, P less than 0.01) after 3 mo. Moreover, whereas before weight loss the ATLPL response to ingested mixed meals (delta 0.9) was minimal, in the maintained reduced-obese state a marked increase was seen (delta 12.6, P = 0.02). Thus, because ATLPL is important to lipid filling in adipose tissue, the maintenance of high levels of fasting ATLPL and the increase in enzyme responsiveness in the reduced-obese state could play an important role in the resumption of the obese state, which so commonly follows weight reduction.     

Regional variation in adipose tissue lipoprotein lipase activity: association with plasma high density lipoprotein levels

The associations of adipose tissue lipoprotien lipase (AT-LPL) activity with body fatness and plasma lipoprotein levels were studied in the light of the recently described regional differences in AT-LPL activity. In this regard, heparin-releasable LPL activity was measured in abdominal and femoral adipose tissues of 29 pre-menopausal women. Body fatness variables were all positively correlated with abdominal and femoral AT-LPL activities expressed per 10(6) cells. However, abdominal and femoral AT-LPL activities expressed per unit of cell surface displayed divergent association patterns with body fatness and plasma lipoprotein levels. Indeed, only abdominal AT-LPL activity remained significantly correlated with body fatness variables after adjustment for fat cell surface. Furthermore, whereas abdominal AT-LPL activity tended to be negatively correlated with plasma HDL-cholesterol levels, femoral AT-LPL activity was positively correlated with plasma HDL2-cholesterol (r = 0.40, P less than 0.05) concentration and with the HDL2-cholesterol/HDL3-cholesterol ratio (r = 0.49, P less than 0.01). These results demonstrate the importance of taking into account the regional variation in metabolic activity of adipose tissue when studying its associations with body fatness, and with plasma lipoprotein levels. The lack of association between abdominal AT-LPL activity and plasma HDL2-cholesterol levels lead us to suggest that AT-LPL activity may not be causally related with plasma HDL levels.     

The regulation of adipose tissue and muscle lipoprotein lipase in runners by detraining.

To study the mechanism of lipoprotein lipase (LPL) regulation by exercise, we recruited 16 healthy athletes to undergo a 2-wk period of detraining. Fasting fat and muscle biopsies were performed both before and after the detraining period. In muscle, detraining resulted in a decrease in LPL activity in both the heparin-releasable (HR) (-45%, P < 0.05) and cellular (extractable [EXT]) (-75%, P < 0.005) fractions, with no significant changes in LPL immunoreactive mass and mRNA levels. However, several subjects demonstrated parallel decreases in LPL mass and mRNA levels with detraining, suggesting that there is some degree of heterogeneity in response. In adipose tissue, detraining had the opposite effects on LPL activity. In the HR fraction, detraining resulted in an 86% increase (P < 0.005) in LPL activity, which was paralleled by a 100% (P = 0.02) increase in HR mass. However, there was no significant change in EXT LPL activity or EXT LPL mass. There were no changes in adipose LPL synthetic rate or LPL mRNA levels with detraining. The ratio of adipose tissue/muscle LPL, which may be an important indicator of the tendency for storage of circulating lipids in adipose tissue, increased significantly after detraining. The adipose/muscle LPL ratio was 0.51 +/- 0.17 in the exercising runners, and 4.45 +/- 2.46 in the same runners after detraining (P < 0.05). Thus, detraining of athletes resulted in a decrease in muscle LPL that occurred through post-translational mechanisms, whereas adipose tissue LPL increased, also due to posttranslational changes. This decrease in muscle LPL, coupled with an increase in adipose LPL, yielded a condition favoring adipose tissue storage.     

The effect of estrogen on the lipoprotein lipase activity of rat adipose tissue.

The effect of 17beta-estradiol or progesterone administration on adipose tissue lipoprotein lipase activity was studied in male and ovariectomized female rats. Lipoprotein lipase activity was measured in acetone-ether-extracted preparations of adipose tissue with doubly labeled (14C-fatty acid, 3H-glyceryl) chylomicron triglyceride as substrate. Administration of 17beta-estradiol to male rats lowered adipose tissue lipoprotein lipase activity from 8.22 plus or minus 1.8 U/g (1 U = 1 mumol triglyceride hydrolyzed per h) to 4.96 plus or minus 0.5 U/g in the treated group. Ovariectomy increased adipose tissue lipoprotein lipase activity from 10.4 plus or minus 1.8 U/g in controls to 22.7 plus or minus 4.3 U/g. 17beta-Estradiol administration to ovariectomized rats cuased a marked fall in adipose tissue lipoprotein lipase activity: 17beta-estradiol (2.5 mug/day) lowered the enzyme activity to 9.00 plus or minus 1.2 U/g, whereas 25 mug/day further decreased lipoprotein lipase activity to 3.2 plus or minus 0.6 U/g. Blood triglyceride levels increased from 0.8 plus or minus 0.05 mumol/ml in ovariectomized rats to 1.4 plus or minus 0.09 mumol/ml in 25 mug/day 17beta-estradiol-treated rats. Progesterone administration did not affect adipose tissue lipoprotein lipase activity in either male or ovariectomized rats. Heart and lung lipoprotein lipase activity was unaffected by hormone treatment. We suggest that the rise in blood triglyceride concentrations, which accompanies high palsma estrogen levels, could be due to the marked inhibition of adipose tissue lipoprotein lipase activity.     

高血压肥胖患者血清和脂肪组织脂蛋白脂酶测定及临床意义

目的探讨高血压肥胖患者血清、脂肪组织中脂蛋白脂酶含量与血脂紊乱、胰岛素抵抗、肥胖、高血压等代谢紊乱的关系.方法选取住院的腹部手术患者48例为研究对象,高血压肥胖患者及正常对照组各24例,测定血压、体重指数、腰臀比、血脂、血糖、胰岛素以及血清和大网膜脂肪组织脂蛋白脂酶的含量.结果高血压肥胖组患者的甘油三酯(TG)、胰岛素(INS)、空腹血糖(FBS)均显著高于对照组(P＜0.01),血清脂蛋白脂酶(LPL)含量、高密度脂蛋白(HDL)显著低于对照组(P＜0.01),血清总胆固醇(TC)(P＞0.05)、低密度脂蛋白胆固醇(LDL-C)(P＞0.05)无明显差别.高血压肥胖组大网膜脂肪组织LPL的含量与对照组无显著差别(P＞0.05).血清LPL含量与体重指数(BMI)(r=-0.640,P＜0.01)、腰臀比(WHR)(r=-0.589,P＜0.01)、TG(r=-0.784,P＜0.01)负相关;与胰岛素敏感指数(ISI)(r=0.533,P＜0.01)、HDL(r=0.463,P<0.01)正相关,与TC(r=-0.222,P＞0.05)、LDL(r=-0.213,P＞0.05)无相关性;脂肪组织LPL含量与上述指标均无相关性(P＞0.05).结论肝素前LPL的含量与高血压肥胖患者的发病及代谢紊乱显著相关;脂肪组织LPL含量与血清LPL含量及肥胖高血压患者的代谢紊乱无明显关联.     

Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique.

The role of insulin in the regulation of adipose tissue lipoprotein lipase activity in humans was investigated in 11 normal subjects and compared with the effects of 0.9% saline infusions in five control subjects. After a basal adipose tissue biopsy for lipoprotein lipase activity, insulin was rapidly infused to achieve and maintain serum levels of approximately 70 microunits/ml while plasma glucose was kept at basal concentrations. Free fatty acids in serum fell to 27 +/- 3% of basal by 20 min (t = 5.19, P less than 0.001) and triglycerides decreased to 77 +/- 3% of basal by 80 min (t = 3.76, P less than 0.01). Adipose tissue lipoprotein lipase activity failed to increase significantly above that measured in controls by the first 3 h of the study. By 6 h of the infusion a stimulatory effect of insulin on adipose tissue lipoprotein lipase was found (t = 3.94, P less than 0.01). There was no relationship between the amount of glucose infused and the insulin effect on the enzyme. The increase in adipose tissue lipoprotein lipase activity at 6 h, however, was inversely related to the basal lipase activity (r = -0.690, P less than 0.02). Thus, insulin appears to stimulate adipose tissue lipoprotein lipase activity in humans. This effect of insulin is delayed when compared with antilipolysis and the fall in plasma triglyceride. The inverse relationship between insulin-stimulated adipose tissue lipoprotein lipase activity and basal enzyme activity suggests that adipose tissue itself is the main regulator of the lipase response to insulin.     

Endothelial lipase provides an alternative pathway for FFA uptake in lipoprotein lipase-deficient mouse adipose tissue

Lipoprotein lipase (LPL) is thought to be the only enzyme responsible for the catabolism of triglycerides (TGs) associated with TG-rich lipoproteins in adipose tissue (AT). However, LPL deficiency in humans and induced mutant mice is not associated with decreased fat mass. We investigated whether endothelial lipase (EL), a recently discovered phospholipase, might represent an alternative mechanism for the uptake of phospholipid-derived fatty acids in murine lipoprotein-deficient AT. When LPL was expressed in AT and isolated murine adipocytes, EL mRNA was not detectable. In contrast, mouse AT and isolated adipocytes that lacked LPL expressed large amounts of EL mRNA. The cellular phospholipase activity in LPL-deficient fat pads was increased 4-fold compared with control fat pads and could be inhibited to control levels by a specific EL antibody. Fatty acids produced by EL activity were absorbed by adipocytes and incorporated into the TG moiety of AT. Our results suggest that EL activity in AT and other peripheral tissues might contribute to the tissue uptake of free fatty acids, which could have important implications for the metabolism of plasma lipoproteins.     

The response of the portal vein to an oral glucose load

Changes of total blood flow, velocities, and cross-sectional area in the portal vein before and after oral glucose administration were studied using image-directed Doppler ultrasonography. Portal vein cross-sectional area, flow velocity, and total blood flow increased significantly compared with baseline studies. Relative increase in these values compared with baseline studies (95% confidence intervals) are presented, and future applications of this method are discussed.     

Rapid effect on lipoprotein lipase activity in adipose tissue of humans after carbohydrate and lipid intake.

Glucose or corn oil was given perorally to fasting, young healthy volunteers, and the time course of acute effects on lipoprotein lipase activity (LLA) in adipose tissue, plasma glycerol, triglyceride, insulin, and blood glucose levels was followed. After glucose intake, adipose tissue LLA increased rapidly, reaching a maximum of 80 per cent above initial level after 2 h. Plasma glycerol, reflecting the rate of lipolysis of depot lipids, decreased rapidly, temporally well correlated to the LLA changes. After corn oil intake no significant effect on any of the parameters studied was observed except for an increase in the plasma triglyceride level caused by the influx of dietary lipid.     

Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load

Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.     

胰岛素抵抗人群皮下脂肪组织中脂肪甘油三酯脂酶和激素敏感性脂肪酶表达减低

目的 通过检测胰岛素抵抗人群皮下脂肪组织中脂肪甘油三酯脂酶(ATGL)和激素敏感性脂肪酶(HSL)的表达,探讨脂肪动员异常与胰岛素抵抗的关系及在胰岛素抵抗中的作用.方法 选则本院择期行腹腔镜胆囊切除术的住院患者55例,根据胰岛素抵抗指数,将患者分为胰岛素敏感组27例和胰岛素抵抗组28例.在手术过程中取皮下脂肪组织.采用半定量逆转录聚合酶链反应测定脂肪组织中ATGL、HSLmRNA的表达,采用Westernblot法测定脂肪组织中ATGL、HSL蛋白的表达.结果 胰岛素抵抗组的体质量指数、腰臀比、血清甘油三酯、血清空腹胰岛素及游离脂肪酸水平均明显高于胰岛素敏感组,体质量指数25.31±1.54 vs 23.11±1.03,腰臀比0.98±0.24 vs 0.75±0.15,甘油三酯(1.98±0.56)mmol/L VS(1.04±0.24)mmol/L,空腹胰岛素(25.87±14.21)mU/LVS(11.15±4.67)mU/L.游离脂肪酸(1.35±0.46)mmol/L vs (0.66±0.23)mmol/ L(P<0.01).胰岛素抵抗组皮下脂肪组织中ATGL mRNA和蛋白表达均明显低于胰岛素敏感组,0.92±0.13 vs 2.03±0.21、1.03±0.08 vs 1.98±0.11(P<0.01);HSL mRNA和蛋白表达也均明显低于胰岛素敏感组,1.35±0.21 vs 1.64±0.12、1.25±0.09 VS 1.42±0.15(P<0.01).ATGL的蛋白表达与空腹胰岛素、胰岛素抵抗指数及游离脂肪酸呈负相关(r=-0.235、-0.356和-0.214,P<0.01或<0.05);HSL 的蛋白表达与空腹胰岛素、游离脂肪酸和腰臀比呈负相关(r=-0.185、-0.246和-0.145,P<0.01或<0.05).结论 胰岛素抵抗状态时皮下脂肪组织中ATGL和HsL的表达减低.     

Effects of intravenous somatostatin and motilin on the blood glucose and hormonal response to oral glucose

Exogenous intravenous infusions of control saline, somatostatin, motilin and somatostatin and motilin together were compared in normal volunteers for their effects on the rise of blood glucose following 50 g oral glucose and for their effects on gastric emptying and plasma hormone concentrations. All regulatory peptide infusions increased the rate of gastric emptying by between 182% and 198% at 60 min post-ingestion. The glucose response during the oral glucose tolerance test was suppressed when somatostatin with or without motilin was infused but was increased during motilin. The somatostatin infusion reduced concentrations of motilin, insulin, gastric inhibitory polypeptide, gastrin and neurotensin whilst the motilin infusion was associated with an increased initial rise in insulin and gastric inhibitory polypeptide. The metabolic effects of the motilin infusion were overriden by the effects of somatostatin when both peptides were infused together; this suggests that somatostatin inhibits both the effects and secretion of motilin.     

High-density lipoprotein cholesterol, hepatic lipase and lipoprotein lipase activities in thyroid dysfunction--effects of treatment

We have investigated the effects of hyper- and hypothyroidism (clinical and subclinical) on lipid metabolism, with special emphasis on serum high-density lipoprotein cholesterol, post-heparin plasma hepatic lipase and lipoprotein lipase activities. In 16 patients with hyperthyroidism, increased post-heparin plasma hepatic lipase activity, decreased serum total cholesterol and serum high-density lipoprotein cholesterol were found while lipoprotein lipase activity and serum triglyceride were normal. In six patients with overt hypothyroidism serum total cholesterol and triglyceride were increased, post-heparin plasma hepatic lipase and lipoprotein lipase were decreased while serum high-density lipoprotein cholesterol was normal. In six patients with subclinical hypothyroidism, serum total cholesterol was increased, serum high-density lipoprotein cholesterol was decreased, while serum triglyceride, post-heparin plasma hepatic lipase and lipoprotein lipase were normal. When the three groups of patients became euthyroid, serum total cholesterol, serum triglyceride, post-heparin plasma hepatic lipase, lipoprotein lipase, and serum high-density lipoprotein cholesterol reverted to normal except for serum high-density lipoprotein cholesterol in the hyperthyroid group which showed no significant change with treatment. A positive correlation was found between serum T3 and post-heparin plasma hepatic lipase while negative correlations were found between serum total cholesterol and serum T3, post-heparin plasma hepatic lipase and serum total cholesterol, lipoprotein lipase and serum triglyceride respectively. Thus in these patients with thyroid dysfunction, significant reversible alterations in serum total cholesterol, triglyceride and high-density lipoprotein cholesterol were found and could be correlated with the observed changes in the activities of hepatic lipase and lipoprotein lipase.