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PubMed1996

Body composition and tissue distributions in growth hormone deficient adults before and after growth hormone treatment.

This study examines short and long-term effects of recombinant human growth hormone (rhGH) on body composition and regional tissue distributions by using a multicompartment technique based on computed tomography. Part I includes nine subjects aged 46 +/- 9 years with adult onset GH deficiency who were examined before and in the end of 6 months treatment with rhGH (0.4 U.kg-1.week-1) in a double-blind crossover trial. Part II is an ongoing open trial including seven of the males in part I. They were treated with rhGH (0.25 U.kg-1.week-1) over an additional period of 24 months. Adipose tissue (AT) was reduced by 4.7 kg (p < 0.01) while the muscle plus skin compartment (M) and visceral organs (V) were increased by 2.4 (p < 0.05) and 0.7 kg (p < 0.01), respectively, over 6 months of treatment with a high rhGH dose. A preferential lipid mobilization occurred in the visceral and subcutaneous trunk depots resulting in a changed AT distribution. Muscles of legs and arms increased while the increase of trunk muscles did not reach significance. The body composition changes were maintained over 2 years additional treatment. The preferential loss in visceral AT was further pronounced while other changes in tissue distributions observed during the first 6 months tended to be reversed on the lower rhGH dosage. It is concluded that growth hormone has profound and discordant effects on AT, M and V and with associated changes in tissue distributions. The beneficial effects on body composition seen in short-term treatment is preserved throughout an additional 24 months period of treatment.

Adipose Tissue↗
PubMedDate not supplied

Significance of mirex-caused hypoglycemia and hyperlipidemia in rats.

Treatment of rats with mirex (40 ppm in diet) caused hypoglycemia, liver enlargement, and inhibition of adrenal corticosteroid-synthesizing enzyme activity. At toxic dosages (20,000 ppm mirex in diet, which has a lethal toxicity-50 [LT-50] of ten days) poisoned female rats showed severe hypoglycemia, fatty liver, adrenal hyperplasia, hypophagia, lipid mobilization, and body weight (bw) loss. A 50 micrograms/kg intraperitoneal (IP) dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in male rats caused similar effects two days posttreatment. Hypoglycemia could be overcome by prednisone (which also inhibited adrenocorticoid-synthesizing enzyme activities) but not by streptozotocin treatment, indicating that hypoglycemia may be related to glucocorticoid deficiency resulting from inhibition of their synthesis and not by direct effects on pancreatic beta-cells. Glucocorticoid deficiency could also cause increased release of adrenocorticoid hormone (ACTH), which may enhance fat mobilization caused by hypophagia.

Adrenal Glands↗
PubMed2004

Fatty acid synthase: a metabolic oncogene in prostate cancer?

In 1920, Warburg suggested that tumors consistently rely on anaerobic pathways to convert glucose to ATP even in the presence of abundant oxygen [Warberg, 1956] despite the fact that it is less efficient for energy supply than aerobic glycolysis. The reasons for this remain obscure to date. More often than not, the microenvironment of solid tumors contains regions of poor oxygenation and high acidity. In this context hypoxia can act in an epigenetic fashion, inducing changes in gene expression and in metabolism for survival. It is reasonable to assume that only the tumor cells capable of developing an unusual tolerance to limiting oxygen availability and to the acidosis resulting from excessive lactate production, can survive. In addition to the striking changes that occur in glucose metabolism, studies in human cancer patients suggest that there is often also an increase in free fatty acid turnover, oxidation and clearance [Legaspi et al., 1987; Hyltander et al., 1991]. For instance, a lipid mobilizing factor produced by tumor cells appears to be responsible for the increase in whole body fatty acid oxidation [Russell and Tisdale, 2002]. Fatty acids synthesis in tumor tissues also occurs at very high rates, as first demonstrated more than half a century ago [Medes et al., 1953]. Importantly, (14)C glucose studies have shown that in tumor cells almost all fatty acids derive from de novo synthesis despite adequate nutritional supply [Sabine and Abraham, 1967; Ookhtens et al., 1984; Weiss et al., 1986]. In addition, tumors overexpressing fatty acid synthase (FAS), the enzyme responsible for de novo synthesis of fatty acids, display aggressive biologic behavior compared to those tumors with normal FAS levels, suggesting that FAS overexpression confers a selective growth advantage. Here, we will review the roles that FAS plays in important cellular processes such as apoptosis and proliferation. In addition, speculations on the putative role of FAS in the altered metabolic pathways of prostate cancer cells will be explored. Because of the frequent overexpression of this enzyme prostate cancer, FAS constitutes a therapeutic target in this disease.

Apoptosis↗
PubMed2005

Alterations of lymphocyte membranes during HIV-1 infection via multiple and simultaneous entry strategies.

Human immunodeficiency virus type 1 (HIV-1) must bind to and enter lymphocytes to replicate and cause the acquired immunodeficiency syndrome. The association of viral particles with the lymphocyte plasma membrane may vary according to a multitude of unknown variables, including lymphocyte membrane receptor mobilization, lipid raft aggregation, clathrin, caveolin, endosomes, microendosome-mediated penetration or penetration through a hole in the membrane. The time course of this delivery appears to be short. Fusion of the virion membrane and lymphocyte plasma membrane leads to destabilization of the lymphocyte membrane. Five morphological stages of membrane alteration were observed in the infected lymphocytes: (1) swelling, (2) splitting, (3) fusion, (4) breaking, and (5) thinning of the lipid bilayer. These plasma membrane alterations were not contributed by fixation artifacts, because the dimensions and distance between the subunits of the surface glycoprotein (SU, gp120) and the transmembrane glycoprotein (gp41) of the viral particles adjacent to the infected cells and processed at the same time remained unchanged. Destabilization of lipid raft patches in the lymphocyte plasma membrane by unknown variables may facilitate HIV-1 penetration of lymphocyte, and other cell types. This a combined review of the pertinent literature with our data showing that HIV-1 may take advantage of multiple penetration approaches simultaneously in the same cell type (H9) to overwhelm the infected cells. The ultrastructural details of H9 cultured cells infected in vitro with HIV-1 contribute to our understanding of viral particle association with the plasma membrane of infected cells.

HIV Infections↗
PubMed2002

Leptin, ghrelin, and energy metabolism of the spawning burbot (Lota lota, L.).

The aim of this study was to investigate the energy metabolism of the burbot (Lota lota, n=38) before, during, and after spawning, which represents the greatest annual metabolic demand for the species. A decrease in body mass, relative weight of the livers, and glycogen concentration of the livers was observed toward the end of spawning. The prespawning period was characterized by high rates of liver glycogenolysis and lipid mobilization. Also, plasma triiodothyronine and sex steroid levels were high before reproduction. During spawning, liver lipolysis was reduced and muscle glycogenolysis stimulated. The levels of triiodothyronine and sex steroids decreased. After reproduction, liver glycogenolysis was suppressed and the rate of gluconeogenesis increased. Thyroid hormone levels were elevated after spawning. Leptin protein and a ghrelin-immunoreactive peptide were detected in burbot plasma. Their concentrations were relatively low before and during reproduction but increased after spawning. The functions of leptin and the ghrelin-immunoreactive peptide in the physiology of the burbot are not consistent with the models of their function in mammals.

Animals↗
PubMedDate not supplied

Localized proton MR spectroscopy of the brain in children.

Small-voxel (3.0-8.0 cm3), magnetic resonance (MR) imaging-guided proton MR spectroscopy was performed in 54 patients (aged 6 days to 19 years) with intracranial masses (n = 16), neurodegenerative disorders (n = 34), and other neurologic diseases (n = 4) and in 23 age-matched control subjects without brain disease. A combined short TE (18 msec) stimulated-echo acquisition mode (STEAM) and long TE (135 and/or 270 msec) spin-echo point-resolved spatially localized spectroscopy (PRESS) protocol, using designed radio-frequency pulses, was performed at 1.5 T. STEAM spectra revealed short T2 and/or strongly coupled metabolites; prominent resonances were obtained from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and total creatine (tCr). Lactate was well resolved with the long TE PRESS sequence. Intracranial tumors were readily differentiated from cerebrospinal fluid (CSF) collections. All tumors showed low NAA, high Cho, and reduced tCr levels. Neurodegenerative disorders showed low or absent NAA levels and enhanced mobile lipid, glutamate and glutamine, and inositol levels, consistent with neuronal loss, gliosis, demyelination, and amino acid neurotoxicity. Preliminary experience indicates that proton MR spectroscopy can contribute in the evaluation of central nervous system abnormalities of infants and children.

Adolescent↗
PubMed1991

Localized proton NMR spectroscopy using stimulated echoes: applications to human skeletal muscle in vivo.

Localized proton NMR spectroscopy using stimulated echoes (STEAM) has been used to study metabolites in different proximal skeletal muscles of normal volunteers at rest. Single scan water-suppressed proton NMR spectra obtained at 1.5 and 2.0 T (Siemens Magnetom) from a 64-ml volume-of-interest (VOI) yield resonances due to triglycerides, phosphocreatine plus a minor contribution from creatine, and betaines comprising carnitine and choline-containing compounds. The observation of the pH-dependent resonances of carnosine required multiple acquisitions and echo times as short as 20 ms. T1 and T2 relaxation times of muscle metabolites were obtained by varying the repetition time and echo time of the STEAM sequence, respectively. Although rather long T2 values such as 180 ms for (phospho-) creatine correspond to natural resonance linewidths of only 2 Hz, the observed linewidths of typically 10-12 Hz are entirely determined by the short T2 relaxation times (25-30 ms) of the water protons used for shimming. The spectroscopic results from 24 muscle studies on 17 young male volunteers show remarkable intra- and interindividual differences in the absolute signal intensities of mobile lipids. Further metabolic variations were observed for the relative concentrations of betaines (by a factor of 2) and carnosine (by a factor of 3) when total creatine is assumed to be constant.

Carnitine↗
PubMed1992

Proton relaxation studies of water compartmentalization in a model neurological system.

Proton relaxation measurements from 18 crayfish abdominal nerve cords (a model of human CNS) are used to demonstrate that the transverse (though not the longitudinal) relaxation can be decomposed into four reproducible components that, in conjunction with optical and electron microscopy of the morphology, can be assigned to three water compartments within the cord and possibly to the mobile lipid protons. The assignments are extraaxonal water protons (32 +/- 9% and mean T2 = 600 +/- 200 ms), axonal water protons (59 +/- 12% and mean T2 = 200 +/- 30 ms), intramyelinic water protons (7 +/- 4% and mean T2 = 50 +/- 20 ms), and finally an unsubstantiated assignment of lipid protons (2.0 +/- 2.0% and mean T2 = 7 +/- 4 ms).

Algorithms↗
PubMed1998

Quantitative 1H MRI and MRS microscopy of individual V79 lung tumor spheroids.

In this Communication 1H MRI and MRS microscopy experiments of individual V79 lung tumor spheroids with diameters between 550 and 650 micrometer are reported. The results have been used to determine the T1, T2, and D values as well as the concentrations of water, total choline, creatine/phosphocreatine, and mobile lipids in the viable rims and in the necrotic centers.

Animals↗
PubMed1992

Comparative effects of 6 week fructose, dextrose and starch feeding on fat-cell lipolysis in normal rats: effects of isoproterenol, theophylline and insulin.

The precise effects of fructose feeding on adipose tissue is not clearly known. Consequently, we studied the effects of fructose feeding on stimulated and inhibited in vitro lipolysis. Twenty seven male Sprague Dawley rats, 5 weeks of age, were fed for 6 weeks on one of three diets containing 57% CHO as fructose (F), dextrose (D) or starch (S). At week 6 the epididymal fat pad weights showed no difference between groups. Stimulation of lipolysis by isoproterenol or theophylline showed: decreased sensitivity of adipocytes to isoproterenol, but not to theophylline, in F (p less than 0.05); the maximal responses were decreased, but NS, after stimulation by either isoproterenol or theophylline. The maximal antilipolytic responses to insulin were increased in F (27%) and D (29%) when compared to S (16%), (p less than 0.05). Only, in F there was an increase (NS) in ED50 (0.63 +/- 0.23 ng/ml) compared to D (0.45 +/- 0.18) and S (0.29 +/- 0.18), indicating decreased sensitivity. Nonfasting plasma insulin and triglycerides were increased at the 6th week in F (p less than 0.01), without any change in plasma glucose levels. However, there was no difference in 12 h fasting plasma glucose, insulin or triglycerides. In conclusion, a 6 week 57% fructose containing diet in normal rats led to: 1) decreased lipid mobilization in the epididymal adipose tissue; and 2) increased nonfasting plasma insulin and triglycerides. Thus fructose, under these experimental conditions, seems to have adverse metabolic effects in normal rats.

Adipose Tissue↗
PubMed1980

Evidence that lipolytic peptide B occurs in the ACTH/MSH-cells of the pituitary and in the brain. An immunocytochemical study of its distribution in correlation to the distribution of neurophysin.

Several lipid-mobilizing peptides occur in the pituitary, among them beta-lipotropin and "lipolytic peptide A and peptide B". The latter two peptides are distinct from beta-lipotropin and appear to be chemically related to the neurophysins. Immunohistochemistry has now revealed that the lipolytic peptide B of the pituitary is localized in the ACTH- and MSH-cells. In addition, immunoreactive peptide B was found in axons of the posterior lobe of the pituitary. Immunoreactive peptide B was found also in nerve fibers and nerve cell bodies in the hypothalamus, particularly in the hypothalamo-hypophyseal tract and in the magnocellular neuronal system. Immunoreactive nerve fibers were numerous also in the periventricular nucleus of the thalamus. The antiserum against peptide B cross-reacts with neurophysin I, and hence, it cannot be excluded that at least part of the immunostaining in the brain reflects the presence of the latter component. However, the regional distribution of immunoreactive peptide B and neurophysin was not identical. Therefore, it is possible that authentic peptide B occurs not only in the pituitary but also in the brain.

Adrenocorticotropic Hormone↗
PubMed1996

Modified adipokinetic peptides containing two tryptophan residues and their activities in vitro and in vivo in Locusta.

Locusta migratoria has three adipokinetic hormones, adipokinetic hormone-I, II and III. Adipokinetic hormone-III ( or = 5.33 x 10(-10)mol x 1(-1)) at inhibiting acetate uptake into locust fat body in vitro, especially so when it is only moderately potent in mobilizing lipid in vivo. The Trp7 in adipokinetic hormones-III, alongside the Trp8 characteristic of adipokinetic hormones, is not seen in any other adipokinetic hormones. To test whether this is hormone-III in the assay in vitro, novel peptides were synthesised to include or remove this structural motif. Thus <QLNFTPWWGTa (Trp7-Locusta-adipokinetic hormone-I or [Gly8a-Thr8b]-Locusta-adipokinetic hormone III); <QLNFTPNWa (des[Gly9-Thr10]- Locusta-adipokinetic hormone-I or Asn7-Locusta-adipokinetic hormone III); <QLNF-SAWWa (Trp7-Locusta-adipokinetic hormone-II) and <QVNFSTWWa (Trp7-Acheta-adipokinetic hormones) were tested both in vitro and in vivo. Except for Trp7-adipokinetic hormone-I in the acetate uptake assay, each of these analogues is less potent then its respective parent, irrespective of the assay. However, the acetate uptake response is highly tolerant of peptides containing Trp7-Trp8, whereas this motif markedly reduces potency in the lipid assays. The different responses exploited in these assays may be exerted through different receptor populations.

Acetates↗
PubMed1990

Pharmacodynamic effects of chronic yohimbine treatment in healthy volunteers.

The effects of 14 days of treatment with the alpha 2-adrenoceptor antagonist yohimbine on cardiovascular parameters (blood pressure and heart rate), plasma catecholamines, insulin and non-esterified fatty acids (NEFA), and the number of alpha 2-adrenoceptors on platelets have been evaluated. The treatment increased plasma noradrenaline but not adrenaline and did not change the other cardiovascular, metabolic or routine blood parameters. It caused a decrease in the velocity of adrenaline-induced platelet aggregation, although [3H]-yohimbine binding to platelets remained unchanged. Acute administration of yohimbine before the experiment led to a significant increase in plasma noradrenaline and NEFA levels. After the 15 day treatment, acute administration of the same dose of yohimbine had less effect on plasma NEFA and there was no significant change in plasma noradrenaline. The acute lipid-mobilizing effect of yohimbine in healthy volunteers persisted after the 14 days of treatment with no change in other parameters. The prolonged alpha 2-adrenoceptor blockade with yohimbine did not induce any change in platelet alpha 2-adrenoceptors.

Adult↗
PubMed1996

Intracranial tumors in children: small single-voxel proton MR spectroscopy using short- and long-echo sequences.

We report preliminary experience using single-voxel, proton MR spectroscopy (MRS) employing small voxels of interest, in combination with short and long echo-time protocols, for the assessment of primary intracranial tumors in children. We examined 23 children with primary intracranial tumors detected by MRI, and 32 controls with similar ages, using MRS on a 1.5 T system. Localized single-voxel (3.7 +/- 1.3 cc) proton spectra were obtained with short-echo (2,000/18), stimulated-echo (STEAM) and long-echo (2,000/270) spin-echo (PRESS) protocols. All spectra were evaluated qualitatively; 10 tumor and 19 control spectra were processed for peak area quantification. Small voxels of interest were able to account for tissue heterogeneity. Combined acquisition of short- and long-echo spectra increased the number of detectable metabolites. The solid portion of all tumors exhibited reduced N-acetyl-aspartate (NAA), strong contribution from cholines (Cho) and inositols or glycine, minimal presence of total creatine (tCr), enhanced broad mobile lipid resonances and accumulated lactate. Calculated selected metabolite ratios of Cho/tCr and Cho/NAA were substantially increased from control values. The cystic portions of the masses showed only lipid and lactate peaks.

Adolescent↗
PubMed1985

Hypothalamic control of lipid metabolism.

Obesity as a common disorder of lipid metabolism might be caused by defective hypothalamic control as demonstrated by ventromedial lesions or the effect of cholecystokinin application. The hypothalamic proopiomelanocorticotropin is the precursor of hormonal fragments affecting fat mobilisation, the endocrine pancreas and gastrointestinal functions.

Animals↗