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PubMed1989

Changes induced in adrenergic lipolysis by the administration of diethylstilboestrol, oestradiol and clomiphene.

The authors studied changes in adrenergic lipolysis in the epididymal adipose tissue of rats to which diethylstilboestrol and oestradiol combined with the anti-oestrogen clomiphene were administered. The maximum lipid-mobilizing effect of isoprenaline was increased not only by subcutaneously administered diethylstilboestrol, but also by the highest dose of the antioestrogen clomiphene used (p.o., 200 micrograms.kg-1 b.w.). Under the given experimental conditions, with 4 1/2 h incubation of adipose tissue, clomiphene was also effective when added in vitro. Its own oestrogenic effect probably stimulated the lipid-mobilizing action of isoprenaline. On combining the administration of increasing doses of clomiphene (p.o., 1-5 days) with a constant dose of oestradiol (200 micrograms.kg-1, s.c. on the 8th day, i.e. 24 h before the actual experiment), changes in isoprenaline lipolysis depended on the dose of clomiphene. In low doses clomiphene inhibited the stimulating effect of subsequently administered oestradiol on isoprenaline-induced lipolysis, but in large doses (100 and 200 micrograms.kg-1 daily) it potentiated, together with oestradiol, the lipid-mobilizing effect of isoprenaline. The results show that the non-steroid oestrogen diethylstilboestrol and the antioestrogen clomiphene may be included among the hormones capable of altering the response of adipose tissue to sympathomimetics (isoprenaline). We attribute the fact that clomiphene acted either as an antagonist or as an agonist of oestradiol to its combined oestrogenic and anti-oestrogenic effects.

Adipose Tissue↗
PubMed2004

Multi-spin-echo J-resolved spectroscopic imaging without water suppression: application to a rat glioma at 7 T.

Two-dimensional J-resolved spectroscopy may be used to separate resonances which overlap in 1D NMR spectra. Coupled with spectroscopic imaging (SI), it would give unequivocal information on the distribution of such resonances. Multi-echo acquisition decreases the minimum experimental time of such 4D experiments. The water peak may be used for phase and chemical-shift reference. This study aimed to demonstrate the feasibility of J-resolved SI based on a multi-echo sequence and without water suppression, and its ability to separate the peaks for lactate and mobile lipid in a rat glioma. Experiments were performed on rat brain, without water suppression, at 7 T. The water signal was used for correcting the phase of the echoes. A FOCSY-like acquisition was used to collect the first part of the echoes at short echo times. Two different data processing methods were tested to overcome the problem of contaminations of metabolite signals by the intense water signal. Maps of N-acetylaspartate, choline, creatine, lactate and mobile lipids were obtained in vivo on a rat glioma in 70 min. The in-plane resolution was 2 mm2. The 2D spatially resolved, 2D J-resolved spectra enabled the separate mapping of lactate and mobile lipids.

Algorithms↗
PubMed1991

Inhibition of tumour-induced lipolysis in vitro and cachexia and tumour growth in vivo by eicosapentaenoic acid.

Stimulation of lipolysis in murine adipocytes in response to a lipid-mobilizing factor produced by a cachexia-inducing murine adenocarcinoma was inhibited by eicosapentaenoic acid (EPA) with a Ki value of 104 microM. The inhibitory effect was strictly structurally specific, since other related fatty acids of both the (n-3) and (n-6) series were ineffective as inhibitors of the lipolytic process. Induction of lipolysis by both salbutamol and ACTH was also inhibited by EPA, suggesting that the effect is exerted on a step central to the process of lipolysis. Lipolysis induced with the tumour lipid-mobilizing factor was associated with a prolonged elevation of the intracellular level of cyclic AMP in adipocytes, in contrast with ACTH and salbutamol. The elevation of adipocyte cyclic AMP in response to the tumour lipid-mobilizing factor and lipolytic hormones was inhibited by EPA. In vivo, administration of pure EPA to weight losing mice bearing the MAC16 adenocarcinoma completely prevented weight loss and tumour growth rate. In contrast both the other (n-3) fatty acid present in fish oil, docosahexaenoic acid (DHA), and linoleic acid were ineffective in inhibiting weight loss or the growth of the MAC16 tumour. This suggests that inhibition of tumour lipolytic activity accounts for the anticachectic effect of EPA, and that a correlation may exist between the inhibition of cachexia and the inhibition of tumour growth.

Adenocarcinoma↗
PubMed1987

Acute adaptation in adrenergic control of lipolysis during physical exercise in humans.

During prolonged exercise, the free fatty acids derived from adipocyte lipolysis are the principal fuel utilized by muscles. In humans, the lipid mobilization from adipose tissue is mainly regulated by insulin and catecholamines: the latter hormones have both beta-adrenergic stimulatory and alpha 2-adrenergic inhibitory effects on lipolysis. The aim of this study was to determine whether rapid alterations in the peripheral action of the regulatory hormones occur during physical work and whether they are of importance for the enhanced lipid mobilization. The acute effects of exercise on the regulation of lipolysis were investigated in isolated adipocytes removed from the gluteal region of 14 healthy volunteers before and immediately after the exercise period. Exercise induced a 20-35% significant increase in the lipolytic response to noradrenaline alone and in combination with the selective alpha 2-antagonist yohimbine and to the pure beta-agonist isoproterenol in isolated adipocytes. The antilipolytic effects of both the alpha 2-agonist clonidine and insulin were unaffected by exercise. Exercise did not influence the specific adipocyte receptor binding of 125I-cyanopindolol (beta-adrenergic receptor), [3H]yohimbine (alpha-adrenergic receptor), and mono-125I-[Tyr A14]insulin (insulin receptor). In conclusion, a single period of submaximal exercise increases adipocyte lipolytic responsiveness to catecholamines through an increased beta-adrenoceptor-mediated effect at steps distal to the receptor binding. Thus the increased peripheral action of catecholamines may be of importance for the observed enhanced lipid mobilization during physical work.

Adaptation, Biological↗
PubMed1986

Fat metabolism and cancer.

Progressive weight loss and anorexia are frequent phenomena in cancer patients. Although cachexia is an expected occurrence in the terminal stages of nearly all malignancies, it may be a presenting sign when the tumor burden is quite small. Lipid depletion occurs out of proportion to the protein loss and accounts for most of the weight loss in cancer. Lipids, more specifically fatty acids, are the major source of fuel in mammals and may also be used in the synthesis of new cell products. Lipolysis and lipogenesis are under the influence of several important enzymes and peptide hormones that may be modulated by a variety of exogenous factors. There is evidence that cancer patients have lost the normal homeostatic responses to decreased energy intake or starvation that allow a decrease in oxygen consumption and protein sparing. An increase in Cori cycle activity or futile recycling of metabolic products occurs with a net energy expenditure rather than energy production. Clinical studies have shown that the body lipid depletion accompanying tumor progression is not solely secondary to decreased food intake and may be reproduced by the transplantation of certain noninvasive tumors to normal hosts. Elevated basal lipolysis has occasionally been seen early in tumor growth. Such findings suggest the presence of a tumor-associated factor responsible for this increase in lipid mobilization. Some of the potential mechanisms for the altered lipid metabolism seen in cancer have been discussed. Metabolic substrates may be remodeled and directed away from fuel-efficient into energy-requiring pathways. An increased energy expenditure may occur as a result of the energy costs of tumor synthesis, an uncoupling of oxidative phosphorylation, or energy-requiring futile cycling. An overall depletion of lipid may be the final outcome of the inhibition of lipid deposition. TNF/cachectin has recently been found to suppress the activity and synthesis of several key lipogenic enzymes, including lipoprotein lipase. Abnormalities in insulin secretion or sensitivity may be involved in the decrease of fat storage in malignancy. Insulin also exerts a significant antilipolytic effect by its antagonism of hormone-sensitive lipase. Mediators of lipolysis and abnormal lipid metabolism may occur in a number of clinical conditions and include ectopic hormone production, growth factors, and tumor-associated lipolytic factors (lipid mobilizing factor, toxohormone).

Animals↗
PubMed1991

Thermogenic and lipolytic effect of yohimbine in the dog.

1. Lipid mobilization during a hypocaloric diet may be enhanced by a pharmacological approach using alpha 2-adrenoceptor antagonists since these drugs are known to increase sympathetic tone and stimulate lipolysis. Studies were undertaken in the dog in order to evaluate the effects of oral yohimbine administration (alpha 2-adrenoceptor antagonist) on heat production, metabolic, endocrinological and cardiovascular parameters. 2. Acute oral yohimbine (0.25 or 0.40 mg kg-1) provoked an increase in plasma non-esterified fatty acids. The drug increased sympathetic nervous system activity as indicated by the increased level of plasma noradrenaline. These effects persisted during the entire experimental period (4 h). The increase in plasma noradrenaline level was two fold higher with the higher dose of yohimbine (0.4 mg kg-1). The plasma adrenaline level was increased only with the higher dose. 3. Yohimbine transiently increased plasma insulin and the effect was dose-dependent. 4. Yohimbine (0.25 mg kg-1) enhanced heart rate and arterial blood pressure. 5. The effect of yohimbine on oxygen consumption, carbon dioxide and heat production was determined by indirect calorimetry. The drug (0.25 mg kg-1) increased O2 consumption and CO2 and heat production 30 min after its administration and the effect persisted over the experimental period. The respiratory quotient, rather low in the fasting animals, remained unchanged. 6. The present work indicates that thermogenesis and lipid mobilization are enhanced during fasting in the dog by alpha 2-adrenoceptor blockade. Yohimbine also induced a transient increase in plasma insulin level and increased heart rate and blood pressure. The lipid mobilization plus the action on thermogenesis observed after yohimbine draw attention to the putative interest of a2-antagonists in the pharmacological treatment of obesity during restricted calorie intake.

Animals↗
PubMedDate not supplied

Effect of hypothermia on lipolytic processes in blood and adipose tissue of rat.

Short-lasting hypothermia raises the FFA level in the blood and this rise is associated with increased lipid-mobilizing activity and higher lipolytic activity of the serum. Raised FFA level and increased lipid-mobilizing activity of the serum persist even when the degree of general anaesthesia is sufficient for preventing thermogenesis signs (shivering and piloerection) caused by falling body temperature. Beta-adrenergic blockade fails to abolish the effect of lipolysis activation caused by hypothermia. These observations suggest that during hypothermia in the blood of the animals appear factors stimulating lipolysis in the adipose tissue. One of these factors may stimulate tissue lipolysis independently of beta-adrenergic receptors. Insulin blocks significantly lipolytic processes in the adipose tissue of hypothermic animals, but its administration is connected with the danger of hypoglycaemia development.

Adipose Tissue↗
PubMed1991

Protease priming of neutrophil superoxide production. Effects on membrane lipid order and lateral mobility.

Phagocyte superoxide (O2-) response is primed by a variety of physiologic compounds including the neutrophil secretory proteases cathepsin G and elastase. To study whether protease priming of neutrophil O2- response is related to changes in membrane physical state, we examined enzyme effects on the order and lateral mobility of lipid probes in intact neutrophil membranes. Exposure to cathepsin G (5 micrograms/ml) or elastase (10 micrograms/ml) caused a significant decrease in fluorescence anisotropy of the probe trimethylammonium diphenylhexatriene in neutrophil plasma membranes (0.279 to 0.256 for cathepsin G, 0.274 to 0.256 for elastase, p less than 0.02 for both), indicating a decrease in phospholipid chain order in the surface membrane bilayer. Cathepsin G and elastase also caused significant increases in membrane lipid lateral mobility as measured by excimer formation of the fluorescent probe 1-pyrenedecanoic acid (for cathepsin G, a 107% increase, and for elastase, a 44% increase in excimer/monomer fluorescence ratio, p less than 0.001). Enzyme effects on membrane structure were dependent on intact proteolytic activity, and were cell specific; the proteases had no effect on lipid order or lateral mobility in liposomes. In corollary studies, the possible association between the physical state of the polymorphonuclear leukocyte membrane and O2- generation was analyzed with the membrane modifying compounds, linoleic acid, ethanol, and cholesterol. Cell exposure to linoleic acid (1 microM) caused a significant decrease in lipid order and an increase in lipid lateral mobility along with increased O2- production to N-formyl-Met-Leu-Phe (fMLP) (191%) and phorbol myristate acetate (PMA) (39%), p less than 0.02 for each. 3 mM ethanol also augmented O2- response to fMLP (31%) and PMA (48%) and caused a significant decrease in lipid order, but did not affect lipid lateral mobility. Treatment with cholesteryl hemisuccinate (100 micrograms/ml) resulted in increased lipid order and decreased lipid lateral mobility, as well as decreased neutrophil superoxide response to fMLP (-61%, p less than 0.001) and PMA (-50%, p less than 0.02). We then examined whether modulation of membrane physical state may explain the mechanism of action of a known priming agent by studying the effects of low concentrations of a diacylglycerol. Cells treated with 10 microM 1-oleoyl-2-acetyl-sn-glycerol had a greater than 8-fold increase in superoxide response to fMLP (p less than 0.001) while demonstrating a significant decrease in lipid order (0.289 to 0.281, p less than 0.01) and a 50% increase in lipid lateral mobility (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1996

Carbohydrate induced modulation of cell membrane. V : ESR characterization of molecular mobility in lipid bilayer of human neutrophil plasma membrane.

Physiological changes in neutrophils after binding of sialic acid, mucin and fucoidan have been investigated using spin probes. Binding of sialic acid markedly reduces the mobility of neutrophil membrane proteins and lipids. Binding of mucin and fucoidan totally restricts the mobility probably due to cross linking of the surface lectins. Binding of these ligands also resulted in an increase in the cytoplasmic viscosity.

Carbohydrate Metabolism↗
PubMed1998

Isolation of a bioactive Ca(2+)-mobilizing complex lipid from bovine vitreous body.

Vitreous body extracts show a potent Ca(2+)-mobilizing activity on fibroblast cells. This Ca2+ signal is complex, and due to the presence of two different bioactive substances. The first one was identified as acid FGF. The second one was shown to be a low molecular weight substance identified as a complex lipid by a combination of chromatographic and biochemical data. This finding raises the possibility that non-classical substances with growth factor-like activity might play a role in the regulation of proliferative processes in the eye.

Animals↗
PubMed1981

Metabolism of sheep adipose tissue during pregnancy and lactation. Adaptation and regulation.

1. Changes in the mean volume, the rate of fatty acid and acylglycerol glycerol synthesis, the activity of lipoprotein lipase and the numbers and affinities of insulin receptors of subcutaneous adipocytes are reported for sheep at different stages of pregnancy and lactation. In addition, the serum concentrations of insulin, progesterone, prolactin, choriomammotropin, somatotropin, glucose, acetate, L-lactate, glycerol and unesterified fatty acids are reported for these sheep. 2. A switch from lipid accumulation to net lipid mobilization accompanied by a decline in the capacity for lipid synthesis, occurred at the onset of the last third of pregnancy. Net lipid mobilization continued during lactation. 3. The changes that occurred in the serum concentrations of the various hormones listed above are discussed in relation to their possible roles in the modulation of adipose tissue metabolism in sheep during pregnancy and lactation. The observations are compared with those from previous studies on the hormonal control of adipose tissue metabolism in the rat during pregnancy and lactation.

Adaptation, Physiological↗
PubMed1998

Short echo-time proton magnetic resonance spectroscopy in regions of severe HIV-related diffuse white matter abnormality on MRI.

The purpose of this study was to determine whether short echo-time proton magnetic resonance spectroscopy (H-MRS) could detect mobile lipid resonances attributable to myelin breakdown products in the deep cerebral white matter of patients with AIDS who have severe diffuse/patchy white matter hyperintensity on T2-weighted magnetic resonance imaging (MRI). Seven patients with AIDS and clinical HIV-associated dementia complex (HADC) and 12 male controls were studied at 1.5T using a single 8 ml voxel, gradient localised, stimulated echo acquisition mode (STEAM) spectroscopy sequence. Spectra were acquired at an echo time of 20 ms with a repetition time of 5000 ms. No spectroscopic peaks were identified at 0.9 ppm and 1.3 ppm (corresponding to lipid resonances) in 6 of the 7 patients with AIDS or in any of the controls. Lipid resonances were identified in 1 patient who had been taking anti-retroviral therapy for 8 weeks. Follow up MRI/H-MRS, performed after a further 14 weeks of anti-retroviral therapy, showed partial resolution of white matter hyperintensity and lipid resonances were not detectable. These data suggest that mobile lipids are only rarely detected by H-MRS in patients with HADC and abnormalities on MRI and that their presence may be transitory.

AIDS Arteritis, Central Nervous System↗
PubMed1997

Feline hepatic lipidosis.

Hepatic lipidosis occurs when lipid mobilized to the liver exceeds lipid leaving the liver via formation of very-low-density lipoproteins or by oxidation. Hepatic lipidosis in cats is associated with overt liver dysfunction. In affected cats, excess lipid is mobilized to the liver because of starvation. Removal of hepatic lipid may be impaired because of protein malnutrition, a relative carnitine deficiency, or oxidative damage to peroxisomes and other hepatic organelles. Hepatic lipidosis occurs in adult cats, and is manifest by signs of weight loss, depression, vomiting, and icterus. Diagnosis is achieved by evaluating laboratory and diagnostic imaging data, in conjunction with a liver biopsy. Aggressive tube feeding is the treatment of choice. With this treatment, survival rates are 60% to 80%.

Animals↗
PubMed1983

Role of the adrenal glands in insulin-induced free fatty acid mobilization in the chicken.

The effects of the administration of insulin on plasma free fatty acid (FFA) levels of adrenalectomized and sham-operated (SO) chickens were compared in order to determine if the lipid-mobilizing action of the hormone is mediated by the adrenal glands. Plasma FFA levels of adrenalectomized and SO chickens were the same before hormone administration (0.69 +/- 0.03 vs 0.72 +/- 0.03 mu Eq/ml, N = 15 for each group). Injection of insulin (1 U/kg, iv) caused a significant increase of plasma FFA of SO chickens (103%) but did not modify FFA levels of adrenalectomized chickens. Blood sugar levels were higher in SO than adrenalectomized birds (163 +/- 4 vs 126 +/- 3 mg/100 ml, N = 9 for each group) before insulin administration but the magnitude of the reduction of blood sugar induced by insulin was similar for both groups. The marked lipolytic effect of glucagon (0.2 mg/kg, iv) on intact chickens was affected only to a small extent by adrenalectomy but, in contrast, the blood sugar response to glucagon was greatly reduced (27%) in adrenalectomized chickens. Significant increases (38%) in plasma FFA levels of intact chickens were obtained during the first few hours after a single intravenous injection of hydrocortisone (10 mg/kg, iv). The data show that the presence of the adrenal glands is essential for the increase in plasma FFA induced by insulin in chickens, and suggest that the lipid-mobilizing effect of the hormone in this species is due to an increased secretion of endogenous glucocorticoids following insulin-induced hypoglycemia.

Adrenal Glands↗
PubMed2002

Norepinephrine transporter function and autonomic control of metabolism.

Genetic variability, numerous medications, and some illicit drugs influence norepinephrine transporter (NET) function; however, the metabolic consequences of NET inhibition are poorly understood. We performed a randomized, double-blind, cross-over trial in 15 healthy subjects who ingested 8 mg of the selective NET inhibitor reboxetine or placebo. Energy expenditure and substrate oxidation rates were determined by indirect calorimetry before and during iv infusion of 0.25, 0.5, 1, and 2 micro g isoproterenol/min. Adipose tissue metabolism was studied by microdialysis before and during local isoproterenol perfusion. At rest, energy expenditure and substrate oxidation rates did not differ between reboxetine and placebo treatment. At 1 micro g/min isoproterenol, energy expenditure was significantly increased in men (+15%) and women (+20%) with both reboxetine and placebo treatment. However, carbohydrate oxidation rate was significantly higher with reboxetine compared with placebo. Baseline and isoproterenol-stimulated adipose tissue blood flow was about 2-fold higher with reboxetine vs. placebo. Furthermore, glucose supply and metabolism was significantly increased and lipid mobilization much more stimulated in adipose tissue under reboxetine when compared with placebo at all isoproterenol concentrations used. We conclude that acute NET inhibition increases adipose tissue glucose uptake and metabolism. While lipid mobilization is increased, overall lipid oxidation is decreased during beta-adrenergic stimulation. This effect cannot be explained by increased systemic or adipose tissue norepinephrine concentrations. Instead, NET inhibition may sensitize adipose tissue to beta-adrenergic stimulation.

Adipose Tissue↗
PubMed1997

Tertiary ammonium ion induces contraction of rat aorta segments and increases the mobility of lipids in the membrane of rat aorta smooth muscle cells.

The effects of tertiary ammonium ion--IEM-1194 (decyldiisopropylammonium bromide)--on smooth muscle cells (SMC) isolated from rat aorta were investigated. Using the patch-clamp technique in the cell-attached configuration, two types of effects on the Ca(2+)-activated K+ channels were recorded after application of IEM-1194: an increase in the number of fast transition bursts in open channels and the prolongation of the burst. The removal of the agonist led to the activation of these channels. Mechanical responses of aortic rings were recorded using the method of isometric tension measurements. IEM-1194 (100-400 microM) caused contractions consisting of two phases. The first phase emerged immediately after application of the agonist. The second phase was observed 10-15 min after application. The contraction of the aorta was followed by the relaxation for over 1.5 h. The same results were obtained in the Ca(2+)-free external solution. Measurements of SMC membrane fluidity by the EPR method showed that IEM-1194 induced an increase in the mobility of membrane lipids. Based on these results, we suggest a mechanism of IEM-1194 action on the Ca(2+)-activated K+ channels.

Animals↗
PubMed2005

Local mobility in lipid domains of supported bilayers characterized by atomic force microscopy and fluorescence correlation spectroscopy.

Fluorescence correlation spectroscopy (FCS) is used to examine mobility of labeled probes at specific sites in supported bilayers consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid domains in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). Those sites are mapped beforehand with simultaneous atomic force microscopy and submicron confocal fluorescence imaging, allowing characterization of probe partitioning between gel DPPC and disordered liquid DOPC domains with corresponding topography of domain structure. We thus examine the relative partitioning and mobility in gel and disordered liquid phases for headgroup- and tailgroup-labeled GM1 ganglioside probes and for headgroup- and tailgroup-labeled phospholipid probes. For the GM1 probes, large differences in mobility between fluid and gel domains are observed; whereas unexpected mobility is observed in submicron gel domains for the phospholipid probes. We attribute the latter to domain heterogeneities that could be induced by the probe. Furthermore, fits to the FCS data for the phospholipid probes in the DOPC fluid phase require two components (fast and slow). Although proximity to the glass substrate may be a factor, local distortion of the probe by the fluorophore could also be important. Overall, we observe nonideal aspects of phospholipid probe mobility and partitioning that may not be restricted to supported bilayers.

G(M1) Ganglioside↗
PubMed1993

Time-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on serum and urine levels of malondialdehyde, formaldehyde, acetaldehyde, and acetone in rats.

The ability of TCDD to produce lipid mobilization and alter lipid metabolism is well known. Previous studies have indicated that TCDD induces an oxidative stress and enhances lipid peroxidation. However, the products resulting from altered lipid metabolism in response to TCDD have not been studied. We have examined the time-dependent changes in serum and urine levels of malondialdehyde, formaldehyde, acetaldehyde, and acetone in response to a single oral 50 micrograms/kg dose of TCDD in rats. The changes in these four metabolic products were quantitated by high-pressure liquid chromatography (HPLC). The effects of TCDD were compared in ad libitum-fed control animals and pair-fed animals. Serum and urine levels of the four metabolites were assayed on Days 0, 3, 6, 9, and 12. Following TCDD administration, significant increases in the four metabolites present in serum and urine were observed at all time points. For example, on Day 6 post-treatment malondialdehyde, formaldehyde, acetaldehyde, and acetone increased approximately 1.8-, 1.4-, 2.0-, and 3.0-fold in serum, respectively, and 1.3-, 1.4-, 1.6-, and 2.0-fold in urine, respectively, relative to pair-fed control animals. Increases in the serum and urine levels of the four metabolites were significantly greater for TCDD animals than for pair-fed control animals at most time points. When the serum levels of malondialdehyde as determined by HPLC were compared with the results obtained by the thiobarbituric acid (TBA) colorimetric method, similar time courses were observed although higher results were obtained for the less specific TBA method. The results clearly demonstrate that TCDD causes markedly elevated serum and urine levels of four specific products associated with lipid metabolism.

Acetaldehyde↗