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PubMed1977

Assay and characterization of serum-stimulated lipolytic activity in homogenates of human adipose tissue.

An assay of lipolytic activity in human adipose tissue is described, in which native homogenates of the adipose tissue yield the enzyme, as well as the triglyceride substrate, and the emulsifying phospholipids. The lipolytic activity in the presence of serum is characterized mainly as lipoprotein lipase activity by a pH-optimum of 8.0, by the fact that serum is necessary for full activity, and that it is inhibited by 1 M NaCl and by protamine. At serum concentrations of higher than 50% a marked inhibition of the lipolysis is observed. Noradrenaline, insulin, and heparin have no effect on the serum-stimulated lipolytic activity.

Adipose Tissue↗
PubMed1985

Central histaminergic stimulation of hyperlipemic response in rats under stress.

In rats subjected to a mild stress of immobilization histamine, the H1-receptor agonist 2-pyridylethylamine (PEA), and the H2-receptor agonists 4-methyl histamine (4-MeHA) and impromidine administered intracerebroventricularly (i.c.v.) 1 h prior to stress, intensified the stress-induced increase in serum free fatty acid (FFA) levels. Impromidine was far more potent than histamine and its agonists in increasing hyperlipemia in stressed rats. The hyperlipemic response to histamine was abolished by i.c.v. pretreatment of rats with mepyramine, a H1-receptor antagonist, but was unchanged in rats pretreated with cimetidine or metiamide, H2-receptor antagonists. The increase in serum FFA levels induced in stressed rats by PEA was abolished by mepyramine but the hyperlipemic responses to 4-MeHA and impromidine were not antagonized by cimetidine. These results suggest that central H1-receptor mediate the histamine-stimulated hyperlipemic response in stressed rats.

Animals↗
PubMed2004

Early metabolic changes in metastatic brain tumors after Gamma Knife radiosurgery: 1H-MRS study.

Evaluation of early metabolic changes in metastatic brain tumors after Gamma Knife radiosurgery was performed by long-echo (TR, 2000ms; TE, 136ms; 128-236 acquisitions) volume-selected single-voxel proton magnetic resonance spectroscopy (MRS). Eighty-five brain metastases in 81 patients were investigated before treatment and 16-18h thereafter. Standard metabolic ratios, namely N-acetylaspartate (NAA)/creatine (Cr), phosphorylcholine/glycerophosphorylcholine (Cho)/Cr, NAA/Cho, lactate (Lac)/Cr, and mobile lipids (Lip)/Cr, were calculated, and comparison of their values before and after irradiation was done. No volumetric changes of any neoplasm were found in any case on the next day after treatment. At the same time, significant reduction of Cho/Cr (P < 0.001) and NAA/Cr (P < 0.01) ratios on the proton MRS of the tumor was disclosed. Reduction of Cho/Cr ratio was significantly more prominent in neoplasms with higher pretreatment Cho/Cr ratios (P < 0.001) and heterogeneous contrast enhancement (P < 0.01). Reduction of NAA/Cr ratio was predominantly determined by its pretreatment value (P < 0.001). The observed decrease of Cho/Cr ratio probably reflects inhibition of proliferative activity and early apoptotic cell loss, whereas reduction of NAA/Cr may result from radiation-induced modulation of neuronal activity in the peritumoral brain tissue. Serial proton MRS represents a valuable diagnostic tool for evaluation of metabolic changes in intracranial neoplasms after radiosurgical treatment.

Aged↗
PubMed1982

In vivo and in vitro antilipolytic effects of some various substituted homocysteine-thiolactone-nicotinamides: structure-activity study.

The antilipolytic activity of homocysteine-thiolactone-nicotinamide (ST22) and in 2-chloro (ST71), 6-chloro (ST82) and 6-hydroxy (ST90) derivatives was investigated by evaluation of serum free fatty acids (FFA) and triglycerides (TG) (in vivo) and FFA release from adipose tissue (in vitro). Increased FFA levels in 17-hr fasted rats at 60 min following treatment with 7 . 10(-4) mol kg-1 p.o. were reduced by 70% (ST22), 60% (ST82) and 18% (ST71), whereas ST90 provoked no change; TG levels showed similar changes. Basal FFA release from epididymal rat adipose tissue at 60 min following treatment with 7 . 10(-4) mol kg-1 p.o. of ST22 and ST82 was reduced by 79 and 45%, respectively. Lipid mobilization induced by noradrenaline (NA) was diversely affected by the compounds according to the tests employed: with in vivo experiments, serum FFA levels were reduced by 60, 70, 10 and 5% at 60 min following treatment with ST22, ST82, ST71 and ST90, respectively (7 . 10(-4) mol kg-1 p.o.; NA bitartrate, 2 mg kg-1 s.c.); in vitro, ST22 produced no change, whereas the other compounds induced a significant mobilization of FFA. The results suggest that: (a) antilipolytic activity can be greatly modified when various substituents capable of influencing either the inductive (-I) or the resonance (+M) effect are introduced into the different positions of the pyridine ring; and (b) the lipolysis experiments did not evince any direct relationship between the effects obtained by the in vivo tests and those obtained by the in vitro tests.

Adipose Tissue↗
PubMed2001

Association of polymorphisms in the beta-2 and beta-3 adrenoceptor genes with risk of colorectal cancer in Japanese.

BACKGROUND: The adrenergic receptor system is involved in thermogenesis and in the activation of lipid mobilization in fat cells, and polymorphisms in the beta-2 and beta-3 adrenoceptor genes (BAR2 and BAR3) have been reported to be associated with obesity and insulin resistance. To examine links between polymorphisms in these genes and the risk of colorectal cancer in Japanese, we conducted the present hospital-based case-referent study. METHODS: Mutations of the BAR2 gene at codon 27 (Gln27Glu) and of the BAR3 gene at codon 64 (Trp64Arg) were examined in 131 patients with colorectal cancer (cases) and in 239 cancer-free referents. We also collected information on environmental factors, using a questionnaire approach. Odds ratios (ORs) were estimated with an unconditional logistic model, after adjustment for potential confounding factors. RESULTS: The proportional distribution of the mutations in BAR2 and BAR3 did not differ between cases and referents. Analysis of a subgroup with a higher body mass index showed that the Trp64Arg variant increased the OR (2.63; 95% confidence interval, 1.13-6.11) for colon cancer, but not for rectal cancer, compared with the Trp64 genotype. Altered ORs for colon and rectal cancers with the Gln27Glu variant were not observed in either the subgroup with the lower body mass index or the subgroup with the higher body mass index. CONCLUSION: These findings suggest that the BAR3 polymorphism may alter the susceptibility to colon cancer risk in obese subjects. To confirm this finding, a further study with a larger number of subjects is now required.

Adult↗
PubMed2005

[Magnetic resonance spectroscopy of brain tumours].

Magnetic resonance spectroscopy facilitates non-invasive determination of metabolic changes in vivo. The main metabolites are the neuronal marker N-acetylaspartate (NAA), cholines reflecting membrane turnover, creatine, lactate, and mobile lipids. Primary brain tumours exhibit reduced NAA and increased choline resonances compared to normal brain, and these abnormalities increase with higher malignancy. Increasing choline resonances on follow-up studies correlate with tumour progression, whereas the reduction of initially increased choline resonances indicates a transition from viable tumour to necrotic tissue. Metastases as non-neuroectodermal tumours lack NAA, but demonstrate elevated choline, lactate and lipid resonances. Lymphomas are characterised by massively increased lipid resonances with markedly elevated choline. Prominent alanine resonances are often observed in meningioma. Cystic/necrotic lesions demonstrate elevated lactate regardless of their aetiology. The characteristic finding of prominent resonances from acetate, succinate, and alanine, of leucine, isoleucine and valine in untreated bacterial abscesses allows the differentiation of bacterial abscesses from cystic/necrotic brain tumours.

Biomarkers, Tumor↗
PubMed2001

Diagnostic potential of short echo time MR spectroscopy of gliomas with single-voxel and point-resolved spatially localised proton spectroscopy of brain.

Accurate neuroimaging grading of gliomas is useful for management, but techniques such as MRI and CT are not sufficiently reliable. Necrosis is a consistent, decisive prognostic factor and the key diagnostic criterion for glioblastoma multiforme. MR spectroscopy (MRS) allows noninvasive measurement of metabolites in brain tumours and mobile lipids reflect necrosis. However, short echo-time (TE) spectroscopy has been required for reliable assessment of lipids, since their relaxation times are very short. Recent advances have made it possible to perform short-TE MRS. We attempted to evaluate the significance of short TE spectroscopy as part of routine imaging for diagnosis and grading of gliomas. We performed TE 30 ms MRS in 25 patients with gliomas (grade II six; grade III three; grade IV, 16) and in 19 areas of healthy white matter using proton brain examination/single voxel (PROBE/SV) and point-resolved spatially localised spectroscopy (PRESS). With short-TE spectroscopy, lipid signals were detected in all 16 tumours of grade IV, one grade II (P = 0.0002) and none of grade III (P = 0.001). TE 136 ms MRS, carried out in 20 of these cases, showed lipid signals in only four of 14 grade IV tumours and in none of the other six. N-acetylaspartate/choline (NAA/Cho) ratios were always more than 1.0 in healthy tissues and less than 1.0 in all but one of the gliomas. The mean creatine (Cr)/Cho ratio in each tumour grade was significantly lower than in the healthy tissues. The mean Cr/Cho ratio was also significantly lower in grade IV than in grade II tumours (P < .0005). Considerable overlap in Cr/Cho ratio was observed between grade II and grades III and IV gliomas at long but less so at short-TE MRS. We conclude that short-TE MRS with PROBE/SV and PRESS is of value in grading gliomas.

Adolescent↗
PubMed2003

Lipolysis induced by leptin in rat adipose tissue from different anatomical locations.

The aim of the present work is to compare the lipolytic response of three fat depots (subcutaneous, epididymal and perirenal) to leptin under in vitro conditions in rats. Moreover an assessment of the potential differences between young and mature rats in terms of the response of these tissues to leptin is made. Adipocytes from 6- and 20-wk-old rats were isolated by collagenase digestion and incubated in vitro both in the absence and the presence of either leptin (10(-12)-10(-6) M) or isoproterenol (10(-6) M). Lipolysis was measured by the release of glycerol into the incubation medium over 2 hours of incubation. Adipocytes responded in a dose-dependent manner to leptin concentrations ranging from 10(-12) M to 10(-6) M. The lowest leptin concentration inducing a significant lipolytic effect was 10(-9) M in all tissues. No significant differences in the effect of the maximal concentration of leptin (10(-6) M) were observed among tissues for either age. The lipolytic effect of isoproterenol (10(-6) M) was significantly reduced in adipose tissues from mature rats; in contrast no significant differences in the effect of leptin (10(-6) M) were observed between young and mature rats. In summary, no anatomical-specific differences exist in the response of rat adipose tissue to lipid mobilization induced by leptin. Furthermore, this leptin action is not decreased in mature rats compared with young ones.

Adipocytes↗
PubMed1999

Decrease of subcutaneous adipose tissue lipolysis after exposure to hypoxia during a simulated ascent of Mt Everest.

The purpose of this study was to examine the effects of prolonged hypoxia on adipose tissue lipolysis, in relation to the weight loss usually observed at high altitude. Eight male subjects were exposed for 31 days to gradually increasing hypobaric hypoxia up to the equivalent altitude of 8848 m (Mt Everest) in a decompression chamber, after 7 days at 4350 m for altitude pre-acclimatization. A biopsy of subcutaneous adipose tissue was performed before and after hypoxic exposure, to study in vitro changes in adipose tissue sensitivity. Fat mass, adipocyte volume and spontaneous lipolysis were not impaired by the exposure to hypoxia. The in vitro lipolytic response to epinephrine, isoproterenol, growth hormone (GH) and parathormone (PTH) decreased significantly (P<0.01, P<0.05, P<0.01 and P<0.01 respectively), as did the plasma concentration of free fatty acid (P<0.01). The anti-lipolytic effect promoted by alpha2-adrenergic receptor stimulation (epinephrine with propranolol) was greater after hypoxia (P<0.05), while the anti-lipolytic activity of insulin was decreased (P<0.01). In conclusion, prolonged exposure to hypobaric hypoxia led to a potent reduction in lipid mobilization, through a decrease in the efficiency of beta-adrenergic, GH and PTH lipolytic pathways, as well as an increment in the alpha2-adrenergic-receptor-mediated anti-lipolytic effects.

Adipose Tissue↗
PubMed1999

The contribution of (1)H-magnetic resonance spectroscopy in defining the pathophysiology of multiple sclerosis.

Proton magnetic resonance spectroscopy ((1)H-MRS) is considered a suitable investigation technique for obtaining in vivo information on pathological changes in multiple sclerosis (MS) brain. The main betabolites identified are choline-containing compounds, creatine, N-acetylaspartate (NAA), lactate, mobile lipids, myo-inositol, glutamate and glutamine. Proton spectra may be acquired from localized volumes of interest on single MS lesions or from the entire brain by (1)H-MRS imaging. An increase of choline and lipids (markers of demyelination) and the presence of lactate (marker of acute inflammatory reaction) have been demonstrated in active Gd-enhancing MS plaques. A reduction of NAA (marker of neuronal or axonal damage) has been found in inactive MS lesions. The recent evidence of an early NAA decrease in active plaques and in normal appearing white matter suggests that axonal damage is an early event in the evolution of demyelinating lesions. The correlation between NAA decrease and clinical disability conforms that axonal damage has important functional consequences, and indicates that the prevention of irreversible axonal loss might be a major target for the design and the timing of therapeutical strategies.

Axons↗
PubMed2006

Proton magnetic resonance spectroscopy (MRS) of metastatic brain tumors: variations of metabolic profile.

BACKGROUND: Spectroscopic imaging can be helpful for the noninvasive identification of parenchymal brain tumors. The objective of the present study was the characterization of the metabolic profile of intracranial metastases, based on proton magnetic resonance spectroscopy (MRS). METHODS: One hundred and four metastatic brain tumors were evaluated by long-echo (TR, 2000 ms; TE, 136 ms) single-voxel volume-selected proton MRS. In 83 patients the tumor fraction within the MRS voxel constituted more than 50%. RESULTS: Compared to normal brain, the tumors showed statistically significant decreases of N-acetylaspartate (P < 0.0001), creatine (P < 0.0001), and the [NAA]/choline-containing compounds ratio (P < 0.0001), increases of [Cho] (P < 0.0001) and the mobile lipids/[Cr] ratio (P < 0.0001) and the lactate/[Cr] ratio (P < 0.05), and the more frequent presence of [Lip] (P < 0.0001) and [Lac] (P < 0.0001) resonances. However, the majority of these differences were lost when data for patients whose tumor fraction within the MRS voxel constituted less than 50% were analyzed separately. Determination of the predominant metabolite peak on the MR spectrum [NAA, Cho, Lip] permitted us to define three general metabolic patterns of brain metastases, which, showed statistically significant associations with the size of the neoplasm (P < 0.001), type of its contrast enhancement (P < 0.01), and the extent of perilesional edema (P < 0.05). CONCLUSION: Proton MRS can define metabolically different subsets of metastatic brain tumors, and these characteristics should be taken into consideration during the differential diagnosis of parenchymal brain lesions.

Aged↗
PubMed2004

Adrenergic responsiveness of adipose tissue lipolysis in autonomic failure.

The sympathetic nervous system mobilizes lipids from adipose tissue through stimulation of beta-adrenergic receptors. The increase in lipid supply augments lipid oxidation. Patients with autonomic failure provide a unique opportunity to further elucidate the role of the adrenergic system in adipose tissue metabolism. In 4 patients with severe pure autonomic failure (PAF), in 3 multiple system atrophy patients (MSA), and in 16 healthy young controls, we inserted a microdialysis catheter in abdominal adipose tissue. The catheter was perfused with incremental concentrations of the nonselective beta-adrenoreceptor agonist isoproterenol. Dialysate glucose, lactate, and glycerol were measured to assess glucose supply, glycolysis, and lipolysis, respectively. Basal dialysate glycerol concentrations were 84 +/- 28 microM in PAF and 130 +/- 64 microM in MSA patients. The increase in dialysate glycerol with isoproterenol was identical in PAF and in MSA patients. We found an almost complete overlap in dialysate glycerol concentrations during isoproterenol stimulation between PAF and MSA patients and healthy young control subjects. Our findings suggest that adipose tissue metabolism is remarkably well preserved in patients with chronic sympathetic denervation, both at rest and during local adrenergic stimulation. We propose that beta-adrenoreceptor upregulation is compensated by a desensitization of post receptor mechanisms or by an upregulation of antilipolytic pathways.

Adipose Tissue↗
PubMed1984

Comparison of in vitro and in vivo effects of prazosin on lipid metabolism.

The results of an in vitro study indicate that only nonselective and alpha 2-blocking agents are capable of increasing adrenergic-stimulated lipolysis in human adipose tissue. Concentrations in vivo of total triglycerides, total cholesterol, and low-density lipoprotein and very low-density lipoprotein cholesterol did not change with prazosin treatment. It is suggested that the low affinity of prazosin for the cyclase-coupled alpha 2 receptors in human adipose tissue explains the lack of effect of prazosin on lipid mobilization from tissue to blood and the absence of a change in low-density lipoprotein and very low-density lipoprotein cholesterol in vivo. However, there was a significant increase in high-density lipoprotein cholesterol. The prazosin-related increase in the cholesterol ratio in vivo has been interpreted as a beneficial modification of this risk factor, but is not explained by our in vitro observations.

Adenylyl Cyclases↗
PubMed1990

Metabolic changes during treatment with two different progestogens.

Two triphasic oral contraceptives containing the same amount of ethinyl estradiol in combination with gestodene or levonorgestrel were compared with respect to contraceptive effect, on lipid metabolism and coagulation. Serum concentrations of gestodene, levonorgestrel, ovarian and pituitary hormones, and sex hormone-binding globulin were measured. Thirty-five randomized into two groups receiving either of the preparations. Before treatment and in the third and sixth cycles, blood sample were drawn in the morning while subjects were still in bed to obtain basal conditions. The contraceptive effect and cycle control were good with both preparations, and there were only a few minor side effects. Sex hormone-binding globulin was elevated twofold in the levonorgestrel group and threefold in the gestodene group. The gestodene concentration in serum varied more than the levonorgestrel concentration, but with correction for variations in sex hormone-binding globulin binding, less variability in gestodene and levonorgestrel concentrations were seen. High-density lipoprotein2 cholesterol decreased in the levonorgestrel group but was unchanged in the gestodene group, whereas apolipoprotein A1 increased in the gestodene group but not in the levonorgestrel group. Antithrombin III decreased in the gestodene group but was unchanged in levonorgestrel-treated women. Factor VII increased in both groups but more in the gestodene group. We conclude that gestodene has a positive influence on lipid metabolism, probably because of its lower androgenicity, and a slightly negative influence on coagulation. The latter, however, probably has no clinical relevance.

Adult↗
PubMed1982

Effect of fatty acids on plasma membrane lipid dynamics and cation permeability in neuroblastoma cells.

In this study the effects of experimental modifications of plasma membrane lipid lateral mobility on the electrical membrane properties and cation transport of mouse neuroblastoma cells, clone Neuro-2A, have been studied. Short-term supplementation of a chemically defined growth medium with oleic acid or linoleic acid resulted in an increase in the lateral mobility of lipids as inferred from fluorescence recovery after photobleaching of the lipid probe 3,3'-dioctadecylindocarbocyanide iodide. These changes were accompanied by a marked depolarization of the membrane potential from -51 mV to -36 mV, 1.5 h after addition, followed by a slow repolarization. Tracer flux studies, using 86Rb+ as a radioactive tracer for K+, demonstrated that the depolarization was not caused by changes in (Na+ + K+)-ATPase-mediated K+ influx or in the transmembrane K+ gradient. The permeability ratio (PNa/PK), determined from electrophysiological measurements, however, increased from 0.10 to 0.27 upon supplementation with oleic acid or linoleic acid. This transient rise of PNa/PK was shown by 24Na+ and 86Rb+ flux measurements to be due to both an increase of the Na+ permeability and a decrease of the K+ permeability. None of these effects occurred upon supplementation of the growth medium with stearic acid.

Animals↗