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PubMed2001

Regulation of lipid mobilization and oxidation during exercise in obesity.

Regulation of lipid mobilization and oxidation during exercise in obesity. Exerc. Sport Sci. Rev. Vol. 29, No. 1, pp 42-46, 2001. Obesity is associated with metabolic disorders that may be related to alterations in lipid mobilization and oxidation. Although exercise is essential for successful weight management, the regulation of fatty acid metabolism during exercise in obesity is unclear. This review discusses factors that regulate fat metabolism during exercise and the effects of endurance training on these responses.

Abdomen↗
PubMed2002

Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women.

OBJECTIVE: We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 microg/m(2) min for 60 min). SUBJECTS: Ten obese women from 40.5+/-3.4 y old were selected for this study. Their body weight was 96.4+/-5.7 kg and their BMI was 35.3+/-1.7 kg/m(2). They received a 2.5-2.9 MJ/day formula diet for 28 days. DESIGN: Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis. RESULTS: The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80-100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment. CONCLUSION: The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol- and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects.

Adipocytes↗
PubMed1993

Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue.

The role of alpha-2 adrenoceptors in lipid mobilization and blood flow was investigated in situ using microdialysis of subcutaneous adipose tissue in nonobese healthy subjects. The alpha-2 agonist clonidine caused dose-dependent biphasic response with increased glycerol levels at low clonidine concentrations and decreased glycerol levels at concentrations > 10(-7) mol/liter. Similar results were observed with epinephrine plus propranolol. Clonidine action was unaffected in the presence of labetalol (beta-/alpha-1 antagonist) but completely blunted by the presence of yohimbine (alpha-2 antagonist). The pseudolipolytic effect of clonidine was significantly more pronounced in gluteal as compared with abdominal adipose tissue. When clonidine was added together with the vasodilating agents nitroprusside or hydralazine, the pseudolipolytic effect was abolished and a dose-dependent decrease in dialysate glycerol was observed at all clonidine concentrations (10(-10)-10(-4) mol/liter). When ethanol was added to the perfusate to monitor blood flow, the escape of alcohol from the dialysate was accelerated by 30% with hydralazine or nitroprusside (P < 0.01) and 30% retarded (P < 0.05) by clonidine (10(-10) mol/liter). Thus, the results demonstrate an important role of blood flow for regulating lipid mobilization from adipose tissue in vivo. Alpha-2 adrenoceptor activation causes marked retention of lipids in adipose tissue due to vasoconstriction in combination with antilipoiysis.

Adipose Tissue↗
PubMedDate not supplied

Magnetic resonance spectroscopy and fluorescence microscopy to investigate mobile lipids in sensitive, resistant and reverting K562 cells and their membranes.

The erythroleukaemic K562 cell line and its adriamycin resistant counterpart were used to study resistance, its reversion and their consequences on the levels and localisation of lipids detected in proton nuclear magnetic resonance (NMR) spectra. On whole cells, the mobile lipids giving rise to a NMR signal were significantly decreased in the resistant cells when compared to the sensitive ones; these lipids recovered partially in the reverting cells. According to the spinlattice relaxation times (T1), the lipids detected appeared to be in a similar environment in sensitive and reverting cells. In membrane-enriched fractions, mobile lipid levels were not significantly different in the sensitive and reverting cell lines but decreased in resistant ones. Moreover, lipid droplets stained with a fluorescent Nile red lipophilic probe showed the presence of highly fluorescent particles in the samples in which NMR detected high levels of mobile lipids. These results suggest the participation of cytosolic lipid droplets in NMR signals in drug sensitive and reverting cells and open the question of the relative roles of these droplets and of the membrane lipids in the lipid metabolic pathways associated with drug resistance in cancer cells.

Drug Resistance, Multiple↗
PubMed1991

Plasma catecholamine levels and lipid mobilization induced by yohimbine in obese and non-obese women.

Oral yohimbine administration (0.2 mg/kg) induced lipid mobilization (increase in plasma non-esterified fatty acids, NEFA) in fasting non-obese women (body mass index BMI = 20.2 +/- 0.5, age 35.5 +/- 2.7 years) without significant action on plasma glucose, insulin levels, heart rate or blood pressure during the time-course of the experiment (240 min). Plasma norpinephrine (but not epinephrine) concentrations were increased (100 percent) after oral yohimbine administration. Oral administration of propranolol (40 mg, 60 min before yohimbine) reduced the lipid-mobilizing action of yohimbine (70 percent) during the 60 min following its administration and then totally suppressed its effect until the end of the experimental period (180 min). In fasting obese women (BMI = 36.4 +/- 2.1, age 37 +/- 3.6 years), yohimbine provoked an increase in plasma NEFA levels which was not markedly different from that observed in non-obese subjects. It had no significant effect on plasma glucose, insulin levels, heart rate or blood pressure. Plasma norepinephrine increased in the same proportions. The lipid-mobilizing effect of yohimbine in women is mainly attributable to the increase in synaptic norepinephrine with a resultant increment in lipolysis by beta-adrenergic agonism. In the standard fasting conditions (12 hours) the blockade of the antilipolytic fat cell alpha 2-adrenoceptors seems to be a minor component of the lipomobilizing effect of yohimbine. Morever, when compared with non-obese women, the lipomobilizing effect of yohimbine is not enhanced in obese women.

Administration, Oral↗
PubMed1976

Studies on lipolytic system of human placenta, blood lipids and lipid mobilizing activity in pregnant women and newborns.

Lipolytic activity of human placenta and lipid mobilizing activity (LMA), free fatty acids (FFA) as well as esterified fatty acid (EFA) levels in serum of pregnant women in different periods of pregnancy and in newborn's serum were studied. Lipolytic activity of human placenta is low in the first trimester of pregnancy and increases in samples examined after delivery. The levels of FFA and EFA in blood of pregnant women are significantly increased in the second and third trimester of pregnancy. The newborn's blood lipid level is significantly lower than that in the mother's blood. Lipid mobilizing activity in serum of pregnant women increases especially in the third trimester of pregnancy and is also high in newborn's blood. This may indicate that fatty acids released from newborn's adipose tissue are metabolized as a source of energy.

Adipose Tissue↗
PubMed2001

Co-ordinate regulation of genes involved in storage lipid mobilization in Arabidopsis thaliana.

Molecular genetic approaches in the model plant Arabidopsis thaliana (Col0) are shedding new light on the role and control of the pathways associated with the mobilization of lipid reserves during oilseed germination and post-germinative growth. Numerous independent studies have reported on the expression of individual genes encoding enzymes from the three major pathways: beta-oxidation, the glyoxylate cycle and gluconeogenesis. However, a single comprehensive study of representative genes and enzymes from the different pathways in a single plant species has not been done. Here we present results from Arabidopsis that demonstrate the co-ordinate regulation of gene expression and enzyme activities for the acyl-CoA oxidase- and 3-ketoacyl-CoA thiolase-mediated steps of beta-oxidation, the isocitrate lyase and malate synthase steps of the glyoxylate cycle and the phosphoenolpyruvate carboxykinase step of gluconeogenesis. The mRNA abundance and enzyme activities increase to a peak at stage 2, 48 h after the onset of seed germination, and decline thereafter either to undetectable levels (for malate synthase and isocitrate lyase) or low basal levels (for the genes of beta-oxidation and gluconeogenesis). The co-ordinate induction of all these genes at the onset of germination raises the possibility that a global regulatory mechanism operates to induce the expression of genes associated with the mobilization of storage reserves during the heterotrophic growth period.

Acetyl-CoA C-Acetyltransferase↗
PubMed2000

[Lipid mobilization and energy metabolism: impact of molecular and cellular approaches on the treatment of obesity].

There is strong evidence that reduced sympathetic nervous system (SNS) activity is involved in the etiology of obesity in several animal models of obesity. In humans the situation is more complex but humans with low SNS activity, reduced beta-adrenergic sensitivity, reduced lipid mobilizing efficacy of catecholamines have lowered energy expenditure and are at greater risk of obesity. The SNS with its effect on food intake, lipid mobilization and energy expenditure has a major potential as a target for novel pharmacotherapies in weight reducing strategies. Extended cellular and molecular knowledge about the nature, the distribution and the role of the adrenergic receptors (beta(1)-, beta(2)-, beta(3)-, alpha(2)- and alpha(1)-) existing in tissue effectors involved in the control of lipid mobilization (adipose tissue) and energy expenditure (brown adipose tissue, skeletal muscle) has opened new pathways for pharmacological strategies. In this manuscript, after a summary of current knowledge on the regulation of lipid mobilization and energy expenditure in humans, we briefly review the putative targets and the most recent attempts to develop agents acting at various adrenergic receptor types in SNS effectors or on SNS activity. These include major questions about putative utilization of beta(3)-agonists, alpha(2)-antagonists and beta-antagonists in pharmacotherapy and/or prevention of obesity in humans.

Adipocytes↗
PubMed1992

Effects of nutritional state, insulin, and glucagon on lipid mobilization in rainbow trout, Oncorhynchus mykiss.

The effects of nutritional state, insulin, and glucagon on lipid mobilization were determined in rainbow trout, Oncorhynchus mykiss. In nutritional state experiments, fish were either fed continuously (except 24 to 36 hr prior to experimentation) with commercial trout chow or fasted for 4 weeks. Lipase activity in liver tissue isolated from fasted fish and cultured for 5 hr was greater than that in tissue isolated from fed fish and cultured. The presence of glucose (5.55 mM) in the incubation medium accentuates lipolytic activity in both liver and adipose tissue. Hormone response was assessed both in vivo and in vitro. Salmon insulin was injected into anesthetized fish (fed continuously except 24 hr prior to injections) in 10 microliters of saline/g body weight; final hormone dose was 100 ng/g body weight. Tissue and plasma were sampled 1 and 3 hr after injection. Insulin resulted in depressed plasma FA concentration and reduced hepatic triacylglycerol lipase activity. In vitro effects of hormones were evaluated by incubating liver and adipose tissue pieces in Hanks-MEM. Glucagon (bovine/porcine) directly stimulated lipid breakdown in both liver and adipose tissue. These actions were manifested by enhanced FA and glycerol released into the culture medium and by elevated triacylglycerol lipase activity. Insulin (bovine) generally appeared antilipolytic as this agent inhibited glucagon-stimulated lipase activity and glucagon-stimulated FA release. Furthermore, insulin (in the presence of glucose) reduced net lipolysis, as indicated by glycerol release, compared to control cultures. These results indicate that nutritional state and glucose are important modulators of lipid mobilization and that glucagon and insulin act directly on lipid storage sites to coordinate lipolysis in rainbow trout.

Adipose Tissue↗
PubMed2003

Free fatty acids modulate intermembrane trafficking of cholesterol by increasing lipid mobilities: novel 13C NMR analyses of free cholesterol partitioning.

Cholesterol and free fatty acids in membranes modulate major biological processes, and their cellular metabolism and actions are often coordinately regulated. However, effects of free fatty acid on cholesterol-membrane interactions have proven difficult to monitor in real time in intact systems. We developed a novel (13)C NMR method to assess effects of free fatty acids on molecular interactions of cholesterol within--and transfer between--model membranes. An important advantage of this method is the ability to acquire kinetic data without separation of donor and acceptor membranes. Large unilamellar phospholipid vesicles (LUV) with phosphatidylcholine/cholesterol ratios of 4:1 served as cholesterol donors. Small unilamellar vesicles (SUV) made with phosphatidylcholine were acceptors. The (13)C(4)-cholesterol peak is narrow in SUV, but very broad in LUV, spectra; the increase in intensity of this peak over time monitored transfer. Oleic acid and other long chain free fatty acids [saturated (C12-18) and unsaturated (C18)] dose-dependently increased mobilities of lipids in LUV (phospholipid and cholesterol) and cholesterol transfer rates, whereas short (C8-10) and very long (C24) chain free fatty acids did not. Decreasing pH from 7.4 to 6.5 (+/-oleic acid) had no effect on cholesterol transfer, and 5 mol % fatty acyl-CoAs increased transfer rates, demonstrating greater importance of the fatty-acyl tail over the headgroup. In LUV containing sphingomyelin, transfer rates decreased, but the presence of oleic acid increased transfer 1.3-fold. These results demonstrate free fatty acid-facilitated cholesterol movement within and between membranes, which may contribute to their multiple biological effects.

Biological Transport↗
PubMed1995

[Lipid mobilization, physiopathological and pharmacological aspects].

The lipolysis in adipose tissue is controlled by the hormone-sensitive lipase activity which is dependent on the intracellular cAMP level. In human adipose tissue, cAMP level is increased by catecholamines (through beta-adrenoceptor stimulation) or decreased by insulin, catecholamine (through alpha 2-adrenoceptor stimulation), neuropeptide Y, prostaglandins and adenosine. The mobilization of lipids from adipose tissue is an adaptative mechanism in response to starvation or hypocaloric diet, which involves reduction of the antilipolytic effect of insulin and the increase of catecholamine sensitivity. The regulatory pathways of lipolysis and their adaptation to caloric reduction are not defective in obesity state. Pharmacological approaches proposed for the activation of lipolysis are limited; they mainly consist either to stimulate the fat cell beta-adrenoceptors (beta-sympathomimetic drugs) or to indirectly activate the sympathetic nervous system (ephedrine and its derivatives, methylxanthines, alpha 2-antagonists). However, the side effects elicited by these drugs frequently limit their clinical use.

Adenylyl Cyclase Inhibitors↗
PubMed2005

Differential stiffness and lipid mobility in the leaflets of purple membranes.

Purple membranes (PM) are two-dimensional crystals formed by bacteriorhodopsin and a variety of lipids. The lipid composition and density in the cytoplasmic (CP) leaflet differ from those of the extracellular (EC) leaflet. A new way of differentiating the two sides of such asymmetric membranes using the phase signal in alternate contact atomic force microscopy is presented. This method does not require molecular resolution and is applied to study the stiffness and intertrimer lipid mobility in both leaflets of the PM independently over a broad range of pH and salt concentrations. PM stiffens with increasing salt concentration according to two different regimes. At low salt concentration, the membrane Young's normal modulus grows quickly but differentially for the EC and CP leaflets. At higher salt concentration, both leaflets behave similarly and their stiffness converges toward the native environment value. Changes in pH do not affect PM stiffness; however, the crystal assembly is less pronounced at pH > or = 10. Lipid mobility is high in the CP leaflet, especially at low salt concentration, but negligible in the EC leaflet regardless of pH or salt concentration. An independent lipid mobility study by solid-state NMR confirms and quantifies the atomic force microscopy qualitative observations.

Cell Surface Extensions↗
PubMed1981

Quantitative analysis of the lipid-mobilizing effects of corticotropin, beta 1-24--corticotropin (tetracosactide) and isoprenaline in older rats and rabbits.

The lipid mobilizing effects of corticotropin (ACTH), beta 1-24-corticotropin-tetracosactide (TCA) and isoprenaline (ISO) were studied in parallel experiments in older rabbits (six months, weight 3.5 kg) and rats (age 75-85 days, weight 275 g) in vitro. The results were analysed quantitatively. Compared with the effect in younger rats the lipid mobilizing action of ISO in older animals does not differ. The same applies to the very low ISO lipolytic potency in rabbits. The ACTH intrinsic activity and affinity decrease in aging rabbits, but not in aging rats. At the concentration 1 x 10(-9) mol/l of TCA 35% of its maximum effect is reached in rabbits and almost the maximum in rats. In comparison with the maximum response to ACTH the maximum of TCA is two times higher in rabbits whereas in rats it reaches only 80% of the ACTH maximum. The order of the intrinsic activities is in older rats and rabbits different: ISO much greater than ACTH greater than TCA (1.00:0.81:0.64) in rats and TCA greater than ACTH greater than ISO (1.00:0.53:0.31) in rabbits. The affinity relations TCA greater than ISO greater than ACTH are identical in both species with the ratios of ACTH:ISO:TCA = 1:50:1740 in rats and 1:34:915 in rabbits. TCA exerts the strongest lipolytic potency in rats which is 5.5 times greater than in rabbits. On the contrary the intrinsic activity of TCA in rabbits is the highest. In older rabbits the ACTH adipokinetic intrinsic activity and affinity decrease faster than those in ISO. The species differences especially in relation to ISO also remain preserved in older animals and this applies to the TCA lipolytic effects, which in turn do not seem to change with aging as much as the effects of ACTH. When evaluating the species differences or the sensitivity changes connected with aging in the action of lipolytic drugs, the intrinsic activity and affinity should be considered separately.

Adipose Tissue↗
PubMed1976

[Lipid-mobilizing activity of a synthetic peptide identical to 33-44 fragment of human growth hormone].

The lipid-mobilizing activity of a synthetic peptide, NH2-Phe-Glu-Glu-Ala-Tyr-Ile-Pro-Lys-Glu-Gln-Lys-Tyr-Ser-Phe-COOH, corresponding to the 31-44 amino-acid sequence of human growth hormone, was studied. The peptide stimulated lypolysis upon administration to fasted rats and during incubation with isolated epidiymal adiposed tissue of rat and perirenal adiposed tissue of rabbit. The lipid-mobilizing effect of the peptide,unlike the corresponding effect of the native growth hormone, developed fast and was markedly pronounced 15-30 min after the incubation was started. Direct dependence between the peptide dose logarithm and the effect studied was observed at concentrations of 0.01-10microng/ml during incubation with rat adipose tissue and at 0.001-0.1 microng/ml during incubation with rabbit tissue.

Adipose Tissue↗
PubMed1987

Effects of epinephrine and norepinephrine on lipid mobilization from coho salmon liver incubated in vitro.

The direct effects of epinephrine and norepinephrine (NE) on lipid mobilization were studied in coho salmon liver slices incubated in vitro. Fatty acid (FA) release from liver slices was measured continuously by pH-stat titration. The pH-stat assay system was validated by simultaneous colorimetric measurement of FA and glycerol release. Liver slices incubated in a glucose-free, low buffering capacity medium and stimulated with NE (10(-6) M) exhibited a one proton (titrimetric) to one FA (colorimetric) release profile. Under similar conditions, NE administration also stimulated glycerol release, in the expected three FA (colorimetric) to one glycerol (colorimetric) ratio. NE stimulated FA release from liver slices in a dose-dependent manner; epinephrine did not have a lipolytic effect. The beta-agonist isoproterenol stimulated FA release, whereas alpha-agonists had no effect. Furthermore, the beta-antagonist propranolol inhibited both NE- and beta-agonist-stimulated FA release. Liver triacylglycerol lipase activity was also stimulated by NE. Propranolol inhibited NE-stimulated lipase activity. These results establish the presence of hormone-sensitive lipase in salmon liver and suggest that NE-stimulated lipid mobilization in salmon liver is mediated through beta-adrenergic pathways.

Animals↗
PubMed1977

Effect of different albumin media on the lipid-mobilizing action of sympathicotropic substances in vitro.

The authors studied the effect of adrenotropic substances on lipolysis in rat epididymal adipose tissue in albumin medium in vitro. On using albumins of different origin (human, bovine), the pD2 values for catecholamines differed by more than one order, in correlation to the type of albumin used. The isopropylnorsynephrine pD2 values did not differ. The addition of ascorbic acid (100 microng/ml) raised the catecholamine pD2 values and completely equalized the pD2 values found in both media. The pD2 values for the synephrine derivative did not alter. The propranolol pA2 values were not negatively affected by the addition of ascorbic acid. Ascorbic acid also produced a mild increase in the maximum lipid-mobilizing values obtained with any of the given substances in either medium. It was concluded in the discussion that catecholamines are oxidized at different rates in different albumin media and that this oxidation can be inhibited by adding ascorbic acid. Ascorbic acid likewise mildly stimulates the maximum lipid-mobilizing effect. The authors recommend the addition of ascorbic acid to albumin medium as a regular component for the study of adrenergic lipid mobilization.

Albumins↗
PubMed2004

(1H) MRS studies of signals from mobile lipids and from lipid metabolites: comparison of the behavior in cultured tumor cells and in spheroids.

(1)H magnetic resonance studies on MCF-7 and HeLa cells were undertaken to reveal differences in lipid and lipid metabolite signals during the growth in culture. High intensity mobile lipid (ML) signals were found during the first days in culture, while afterwards the same signals declined and started increasing again at confluence and at late confluence. At the same time, signals from the lipid metabolite phosphocholine decreased in intensity while signals from glycerophosphocholine in MCF-7 and from choline in HeLa increased as cells approached confluence. Spectral parameters from actively proliferating and non-proliferating cells were used to classify cells with respect to the proliferative conditions by means of a multivariate statistical analysis. Furthermore, it was shown that polyunsaturation of mobile lipid chains was lower in the confluent group with respect to the actively proliferating cells. The examination of spectra from suspensions of MCF-7 spheroids with diameter smaller than 500 microm suggests that cells in spheroids are in condition of lipid metabolism similar to that of confluent cultured cells.

Algorithms↗
PubMed2002

Changes in lipid mobility associated with alamethicin incorporation into membranes.

The binding state of the antibiotic peptide alamethicin with phospholipid bilayers was investigated in terms of the changes induced in lipid mobility. Fluorescence anisotropy was used for the study. It was found that an increase in peptide concentration induced different changes in lipid mobility above and below a critical peptide concentration. This concentration was also critical for an increase in the cooperative binding of the peptide, as detected by circular dichroism. Above the critical peptide concentration, the mobility of both lipid regions, around the polar head and hydrocarbon chain, became restricted with an increased peptide concentration. Below the critical level, however, an increased peptide concentration induced a "wobbling" of the lipid hydrocarbon chain. These results show that an increase in the cooperative binding of the peptide is accompanied by a change in the dominant configuration of the binding peptide. When the binding peptide increases, the dominant configuration appears to shift from surface association to deep incorporation within the membrane. This shift in configuration means that in the formation of ion-conductive pores, voltage-driven insertion of the peptide is a prominent step below a critical peptide concentration.

Alamethicin↗